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Epidemiology

Abstracts of selected papers

Alzheimer's Association. 2009 Alzheimer's disease facts and figures. Alzheimers Dement. 2009 May;5(3):234-70.

Alzheimer's disease (AD) is the sixth leading cause of all deaths in the United States, and the fifth leading cause of death in Americans aged 65 and older. Whereas other major causes of death have been on the decrease, deaths attributable to AD have been rising dramatically. Between 2000 and 2006, heart-disease deaths decreased nearly 12%, stroke deaths decreased 18%, and prostate cancer-related deaths decreased 14%, whereas deaths attributable to AD increased 47%. An estimated 5.3 million Americans have AD; the approximately 200,000 persons under age 65 years with AD comprise the younger-onset AD population. Every 70 seconds, someone in America develops AD; by 2050, this time is expected to decrease to every 33 seconds. Over the coming decades, the "baby-boom" population is projected to add 10 million people to these numbers. In 2050, the incidence of AD is expected to approach nearly a million people per year, with a total estimated prevalence of 11 to 16 million people. Significant cost implications related to AD and other dementias include an estimated $148 billion annually in direct (Medicare/Medicaid) and indirect (e.g., decreased business productivity) costs. Not included in these figures is the $94 billion in unpaid services to individuals with AD provided annually by an estimated 10 million caregivers. Mild cognitive impairment (MCI) is an important component in the continuum from healthy cognition to dementia. Understanding which individuals with MCI are at highest risk for eventually developing AD is key to our ultimate goal of preventing AD. This report provides information meant to increase an understanding of the public-health impact of AD, including incidence and prevalence, mortality, lifetime risks, costs, and impact on family caregivers. This report also sets the stage for a better understanding of the relationship between MCI and AD.

Hall KS, Gao S, Baiyewu O, Lane KA, Gureje O, Shen J, Ogunniyi A, Murrell JR, Unverzagt FW, Dickens J, Smith-Gamble V, Hendrie HC. Prevalence rates for dementia and Alzheimer's disease in African Americans: 1992 versus 2001. Alzheimers Dement. 2009 May;5(3):227-33.

BACKGROUND: This study compares age-specific and overall prevalence rates for dementia and Alzheimer's disease (AD) in two nonoverlapping, population-based cohorts of elderly African Americans in Indianapolis in 2001 and 1992. METHODS: We used a two-stage design. The first stage involves the Community Screening Interview for Dementia (CSI-D). The CSI-D scores are grouped into good, intermediate, and poor performance before selection for clinical assessment. Diagnoses were performed using standard criteria in a consensus diagnosis conference; clinicians were blind to performance groups. In 1992, interviewers visited randomly sampled addresses to enroll self-identified African Americans aged > or =65 years. Of 2582 eligible, 2212 enrolled (9.6% refused, and 4.7% were too sick). In 2001, Medicare rolls were used for African Americans aged >70 years. Of 4260 eligible, 1892 (44%) enrolled, 1999 (47%) refused, and the remainder did not participate for other reasons. RESULTS: The overall age-adjusted prevalence rate for dementia at age > or =70 years in 2001 was 7.45% (95 confidence interval [CI], 4.27-10.64), and in the 1992 cohort, this prevalence rate was 6.75% (95% CI, 5.77-7.74). The overall age-adjusted prevalence rate at age > or =70 years for AD in the 2001 cohort was 6.77% (95% CI, 3.65-9.90), and for the 1992 cohort, it was 5.47% (95% CI, 4.51-6.42). Rates for dementia and AD were not significantly different in the two cohorts (dementia, P = .3534; AD, P = .2649). CONCLUSIONS: We found no differences in the prevalence rates of dementia and AD between 1992 and 2001, despite significant differences in medical history and medical treatment within these population-based cohorts of African American elderly.

Treiber KA, Lyketsos CG, Corcoran C, Steinberg M, Norton M, Green RC, Rabins P, Stein DM, Welsh-Bohmer KA, Breitner JC, Tschanz JT. Vascular factors and risk for neuropsychiatric symptoms in Alzheimer's disease: the Cache County Study. Int Psychogeriatr. 2008 Jun;20(3):538-53. Epub 2008 Feb 21.

OBJECTIVE: To examine, in an exploratory analysis, the association between vascular conditions and the occurrence of neuropsychiatric symptoms (NPS) in a population-based sample of incident Alzheimer's disease (AD). METHODS: The sample consisted of 254 participants, identified through two waves of assessment. NPS were assessed using the Neuropsychiatric Inventory. Prior to the onset of AD, data regarding a history of stroke, hypertension, hyperlipidemia, heart attack or coronary artery bypass graft (CABG), and diabetes were recorded. Logistic regression procedures were used to examine the relationship of each vascular condition to individual neuropsychiatric symptoms. Covariates considered were age, gender, education, APOE genotype, dementia severity, and overall health status. RESULTS: One or more NPS were observed in 51% of participants. Depression was most common (25.8%), followed by apathy (18.6%), and irritability (17.7%). Least common were elation (0.8%), hallucinations (5.6%), and disinhibition (6.0%). Stroke prior to the onset of AD was associated with increased risk of delusions (OR = 4.76, p = 0.02), depression (OR = 3.87, p = 0.03), and apathy (OR = 4.48, p = 0.02). Hypertension was associated with increased risk of delusions (OR = 2.34, p = 0.02), anxiety (OR = 4.10, p = 0.002), and agitation/aggression (OR = 2.82, p = 0.01). No associations were observed between NPS and diabetes, hyperlipidemia, heart attack or CABG, or overall health. CONCLUSIONS: Results suggest that a history of stroke and hypertension increase the risk of specific NPS in patients with AD. These conditions may disrupt neural circuitry in brain areas involved in NPS. Findings may provide an avenue for reduction in occurrence of NPS through the treatment or prevention of vascular risk conditions.

Scarmeas N, Luchsinger JA, Mayeux R, Stern Y. Mediterranean diet and Alzheimer disease mortality. Neurology. 2007 Sep 11;69(11):1084-93.

BACKGROUND: We previously reported that the Mediterranean diet (MeDi) is related to lower risk for Alzheimer disease (AD). Whether MeDi is associated with subsequent AD course and outcomes has not been investigated. OBJECTIVES: To examine the association between MeDi and mortality in patients with AD. METHODS: A total of 192 community-based individuals in New York who were diagnosed with AD were prospectively followed every 1.5 years. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of mortality in Cox models that were adjusted for period of recruitment, age, gender, ethnicity, education, APOE genotype, caloric intake, smoking, and body mass index. RESULTS: Eighty-five patients with AD (44%) died during the course of 4.4 (+/-3.6, 0.2 to 13.6) years of follow-up. In unadjusted models, higher adherence to MeDi was associated with lower mortality risk (for each additional MeDi point hazard ratio 0.79; 95% CI 0.69 to 0.91; p = 0.001). This result remained significant after controlling for all covariates (0.76; 0.65 to 0.89; p = 0.001). In adjusted models, as compared with AD patients at the lowest MeDi adherence tertile, those at the middle tertile had lower mortality risk (0.65; 0.38 to 1.09; 1.33 years' longer survival), whereas subjects at the highest tertile had an even lower risk (0.27; 0.10 to 0.69; 3.91 years' longer survival; p for trend = 0.003). CONCLUSION: Adherence to the Mediterranean diet (MeDi) may affect not only risk for Alzheimer disease (AD) but also subsequent disease course: Higher adherence to the MeDi is associated with lower mortality in AD. The gradual reduction in mortality risk for higher MeDi adherence tertiles suggests a possible dose-response effect.

Luchsinger JA, Tang MX, Mayeux R. Glycemic load and risk of Alzheimer's disease. J Nutr Health Aging. 2007 May-Jun;11(3):238-41.

OBJECTIVE: to explore the relation of glycemic load (GL) with Alzheimer's disease (AD) risk. DESIGN: Cohort study. SETTING: Cohort of elderly subjects in New York City. PARTICIPANTS: 939 persons 65 years and older without dementia followed for an average of 6.3 years. MEASUREMENTS: Glycemic index, carbohydrate and calorie intake were measured using a semi-quantitative food frequency questionnaire (SFFQ). GL was calculated as the product of carbohydrate intake and glycemic index and adjusted for energy intake. AD was ascertained with standard research criteria. RESULTS: Cox regression was used to relate GL quartiles to AD using time from SFFQ to AD as the time-to-event variable. There was no association between GL and AD after adjustment for age, gender, education, ethnic group, and presence of diabetes. There was no evidence of modification by age, gender, APOE-e4, and presence of diabetes. The only dietary variable associated with a higher risk of AD was total calories (HR of AD for a one-log unit increase =2.2; 95% CI: 1.4,3.5) after adjustment for age, gender, ethnic group, education, diabetes, and APOE-e4. CONCLUSION: GL is not associated with a higher risk of AD in the elderly. Our data does not support the popular practice of low carbohydrate diets for the prevention of AD in the elderly.

Kawas CH, Corrada MM. Alzheimer's and dementia in the oldest-old: a century of challenges. Curr Alzheimer Res. 2006 Dec;3(5):411-9.

Alzheimer's disease (AD) is the most common type of dementia in the US and much of the world with rates increasing exponentially from age 65. Increases in life expectancy in the last century have resulted in a large number of people living to old ages and will result in a quadrupling of AD cases by the middle of the century. Preventing or delaying the onset of AD could have a huge impact in the number of cases expected to develop. The oldest-old are the fastest growing segment of the population and are estimated to account for 12% of the population over 65. Establishing accurate estimates of dementia and AD rates in this group is crucial for public health planning. Prevalence and incidence estimates above age 85 are imprecise and inconsistent because of the lack of very old individuals in most studies. Moreover, risk and protective factors in our oldest citizens have been studied little, and clinical-pathological correlations appear to be poor. We introduce The 90+ Study, established to address some of the unanswered questions about AD and dementia in the oldest-old. Our preliminary results show that close to half of demented oldest-old do not have known cerebral pathology to account for their cognitive deficits. Furthermore, the APOE-e4 allele appears to be a risk factor for AD only in the women in our study. In addition to the challenge of preventing and treating AD, the oldest-old will require major investigative energy to better understand the concomitants of longevity, the causes of dementia, and the factors that promote successful aging in oldest citizens.

Bennett DA, Schneider JA, Arvanitakis Z, Kelly JF, Aggarwal NT, Shah RC, Wilson RS. Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology. 2006 Jun 27;66(12):1837-44.

OBJECTIVE: To examine the relation of National Institute on Aging-Reagan (NIA-Reagan) neuropathologic criteria of Alzheimer disease (AD) to level of cognitive function in persons without dementia or mild cognitive impairment (MCI). METHODS: More than 2,000 persons without dementia participating in the Religious Orders Study or the Memory and Aging Project agreed to annual detailed clinical evaluation and brain donation. The studies had 19 neuropsychological performance tests in common that assessed five cognitive domains, including episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. A total of 134 persons without cognitive impairment died and underwent brain autopsy and postmortem assessment for AD pathology using NIA-Reagan neuropathologic criteria for AD, cerebral infarctions, and Lewy bodies. Linear regression was used to examine the relation of AD pathology to level of cognitive function proximate to death. RESULTS: Two (1.5%) persons met NIA-Reagan criteria for high likelihood AD, and 48 (35.8%) met criteria for intermediate likelihood; 29 (21.6%) had cerebral infarctions, and 18 (13.4%) had Lewy bodies. The mean Mini-Mental State Examination score proximate to death was 28.2 for those meeting high or intermediate likelihood AD by NIA-Reagan criteria and 28.4 for those not meeting criteria. In linear regression models adjusted for age, sex, and education, persons meeting criteria for intermediate or high likelihood AD scored about a quarter standard unit lower on tests of episodic memory (p = 0.01). There were no significant differences in any other cognitive domain. CONCLUSIONS: Alzheimer disease pathology can be found in the brains of older persons without dementia or mild cognitive impairment and is related to subtle changes in episodic memory.

Hou CE, Yaffe K, Pérez-Stable EJ, Miller BL. Frequency of dementia etiologies in four ethnic groups. Dement Geriatr Cogn Disord. 2006;22(1):42-7.

BACKGROUND/AIMS: Research on dementia among ethnically diverse populations in the USA has focused primarily on Alzheimer disease and vascular dementia, but there are limited data on other neurodegenerative causes of dementia. METHODS: To determine the frequency of neurodegenerative disorders in four ethnic groups, data collected at Alzheimer's Disease Research Centers of California for assessments between 1992 and 2002 were analyzed retrospectively. Cases of Alzheimer disease, vascular dementia, dementia with Lewy bodies, frontotemporal lobar degeneration, Parkinson disease and progressive supranuclear palsy were identified for 452 Asian and Pacific Islander, 472 Black, 675 Latino and 4,926 White patients. RESULTS: The percentage of non-Whites diagnosed as having dementia with Lewy bodies was lower than that of Whites. Frontotemporal lobar degeneration was as common in Asians and Pacific Islanders compared to Whites, but less common in Blacks and Latinos. Progressive supranuclear palsy was more frequent in Asians and Pacific Islanders compared to Whites, but equally common in Blacks and Latinos. CONCLUSION: Additional study is needed on the social and biological factors that influence the diagnosis and prevalence of non-Alzheimer and nonvascular dementias among diverse ethnic groups.

Buchanan RJ, Wang S, Ju H, Graber D. Analyses of gender differences in profiles of nursing home residents with Alzheimer's disease. Gend Med. 2004 Aug;1(1):48-59.

BACKGROUND: Alzheimer's disease (AD), a progressive, neurodegenerative disorder characterized by memory loss, language deterioration, impairment of visuospatial skills, poor judgment, and indifference, but preserved motor function, is the most common type of dementia, accounting for two thirds or more of all cases of dementia. The identification of differences between men and women with AD might present opportunities to improve the quality of AD-related care provided by nursing facilities, as well as lead to additional analyses of nursing home residents with AD. OBJECTIVE: The objectives of this study were to gain additional insight into gender differences in nursing home residents with AD in the United States, and to provide a better understanding of their health status and the care they receive in nursing facilities. METHODS: All admission assessments recorded in the Minimum Data Set (MDS) throughout the United States during 2000 were analyzed. P values for all significant differences were <0.001. RESULTS: A total of 49,607 residents with a diagnosis of AD (67.9% women) were identified. Female residents with AD were more likely to be older and widowed, whereas male residents with AD were more likely to be married. We found minimal gender differences in cognitive impairment among these residents with AD, although women were more likely to understand and be understood by others. Male residents with AD were more likely to exhibit behavioral symptoms, whereas female residents with AD tended to be more physically impaired and dependent on others for activities of daily living. Significant differences in comorbidities were found between the sexes, with greater proportions of male residents with AD having cardiac-related conditions, stroke, cancer, and other life-threatening chronic conditions. Male residents with AD were more likely to receive care in AD special-care units; daily antipsychotic medications; and intervention programs for mood, behavior, and cognitive loss than female residents with AD. CONCLUSIONS: In this study of nursing home residents identified using the MDS, key differences were found between male and female residents with AD, including age; cognitive and communicative abilities; and mental health, mood, and behavioral patterns.

Krishnan LL, Petersen NJ, Snow AL, Cully JA, Schulz PE, Graham DP, Morgan RO, Braun U, Moffett ML, Yu HJ, Kunik ME. Prevalence of dementia among Veterans Affairs medical care system users. Dement Geriatr Cogn Disord. 2005;20(4):245-53.

OBJECTIVES: In an aging population, the number of veterans diagnosed with dementia is likely to increase. Knowledge of existing dementia prevalence will be beneficial in planning for future patient care needs. Our objectives were to assess the prevalence of the dementia diagnosis among those treated at Veterans Affairs (VA) medical centers and determine how it varies across race and Veterans Integrated Service Network (VISN). MATERIALS AND METHODS: Data were collected on all veterans seen within the VA medical system from 1997 through the first half of 2001. Only veterans aged 65 and over were included in the study. Veterans were included if they had one of the following dementia ICD-9 codes: 290.XX, 291.2, 294.XX, 331.XX, 046.1, or 046.3. RESULTS: The overall prevalence of dementia was 7.3%. The prevalence of dementia was similar among white patients and patients of other races, except African-American patients, in whom it was 50% higher. Across VISNs, the prevalence of dementia ranged from 5.8 to 9.4%. Alzheimer's disease was the most frequently diagnosed type of dementia within the VA, and inpatient service utilization and outpatient psychiatry visits by individuals with dementia were high relative to other VA patients. DISCUSSION: The overall prevalence identified is consistent with that reported in the literature, as is the elevated prevalence in African-Americans versus whites. The data on prevalence by VISN may identify regional variation in either the types of dementia present or the diagnostic criteria used. The dementia diagnosis is clearly associated with substantial service use.

Manton KC, Gu XL, Ukraintseva SV. Declining prevalence of dementia in the U.S. elderly population. Adv Gerontol. 2005;16:30-7.

A decline in chronic disability prevalence occurred 1982 to 1999 in the U.S. elderly population parallel to declines in severe cognitive impairment. Comparative analysis of factors contributing to the incidence of dementia led us to suggest explanations for this decline. 42,000 disabled and non-disabled individuals aged 65+ participating in National Long Term Care Surveys (NLTCS) were drawn from Medicare enrollment lists to ensure the US population aged 65+ is represented. Severe cognitive impairment (SCI) was defined by the subject not being able to successfully answer any cognitive screen questions in survey interviews. This definition thus covered cases of dementia of different origin and clinical manifestation: Alzheimer's, non-Alzheimer's, stroke-related, vascular etc. Age-specific prevalence of SCI was calculated for 1982, 1984, 1989, 1994 and 1999, and Medicare record physician determined diagnoses of vascular, mixed and Alzheimer's dementia in 1994 and 1999 was determined by gender and age. We found 310,000 fewer severely cognitively impaired elderly in 1999 than in 1982. The average decline in prevalence was from 5.7% to 2.9% for this period. This was associated with a significant decline in mixed but not Alzheimer's dementias. On a gender basis, the male proportional decline was larger than that of female. Several possible explanations of such a surprising trend in elderly age dementias are discussed, including (i) increased proportion of better educated people among the oldest old; (ii) recent declines in stroke rates (these may contribute to decreasing risks of post-stroke dementias); (ii) expanding use of neuro-protective medications working prophylactically for selected dementias. A significant component of disability decline in the U.S. elderly population is the decline in vascular and mixed dementias, but not in Alzheimer's disease alone. Improved medical therapies and better education among the old appear to play important roles in this decline.

Taylor DH Jr, Sloan FA, Doraiswamy PM. Marked increase in Alzheimer's disease identified in medicare claims records between 1991 and 1999. J Gerontol A Biol Sci Med Sci. 2004 Jul;59(7):762-6.

BACKGROUND: Epidemiologic evidence suggests that African Americans have higher rates of Alzheimer's disease (AD) than do whites. Examining longitudinal trends in the number of persons who are identified as having AD in administrative databases may provide insights into this phenomenon. METHODS: We analyzed 9-year longitudinal data (1991-1999) for 29,679 Medicare beneficiaries who were screened for the National Long-Term Care Survey. Cases of AD were identified using ICD-9-CM diagnosis codes from Medicare claims files. RESULTS: Age-adjusted rates of Medicare beneficiaries identified as having AD rose from 1991-1999 for all groups studied, but particularly among African Americans. In 1991, African Americans made up 6.5% of the identified AD cases but comprised 11.0% of cases in 1999 (X(2) = 6.79, p =.005). The rate of increase in identification of AD was particularly large for women who were aged 85 years and older. CONCLUSIONS: Reasons for increased identification of AD in Medicare claims is likely multifactorial; sharp increases among African Americans may reflect improved access.

Kang JH, Weuve J, Grodstein F. Postmenopausal hormone therapy and risk of cognitive decline in community-dwelling aging women. Neurology. 2004 Jul 13;63(1):101-7.

BACKGROUND: A randomized trial of postmenopausal women over age 65 reported increased risks of cognitive decline with 4 years of combined estrogen and progestin treatment. However, questions remain, including the effect of longer duration or of hormone therapy initiated at younger ages. METHODS: The Nurses' Health Study is a prospective cohort begun in 1976, comprising 121,700 female nurses who report health information via biennial mailed questionnaires. This substudy includes 13,807 participants age 70 to 81 who completed two telephone cognitive assessments, 2 years apart, between 1995 and 2003. General cognition, verbal memory, category fluency, and attention were tested. Multiple linear regression was used to estimate adjusted mean declines and logistic regression to estimate adjusted risks of substantial decline in cognition (> or =2 SD of baseline performance) across hormone groups. APOE genotype was available in a subset of 3,667 participants. RESULTS: Overall, little difference was found in mean cognitive decline between current hormone users and never users. However, for long-term users of estrogen alone or combined with progestin, increased risk of substantial decline was observed on most cognitive tests (relative risk [RR] = 1.25 to 1.72). Decline was particularly high among women initiating hormones at older ages compared with never users: for example, on our test of general cognition, RR of substantial decline was 1.74 (95% CI 1.08, 2.81) and mean difference in decline was -0.43 (95% CI -0.73, -0.12). No significant interactions between hormone use and APOE epsilon4 allele were observed. CONCLUSION: Postmenopausal hormone therapy provides no appreciable cognitive benefits in older women.

Weiner MF, Rosenberg RN, Svetlik D, Hynan LS, Womack KB, White C 3rd, Good S, Fuller C, Wharton D, Richter R. Comparison of Alzheimer's disease in Native Americans and Whites. Int Psychogeriatr. 2003 Dec;15(4):367-75.

OBJECTIVE: This study compared medical history and findings on initial clinical examination in Native Americans diagnosed with possible or probable Alzheimer's disease (AD) at Native American satellite clinics of the University of Texas (UT) Southwestern Medical Center's Alzheimer's Disease Center with those of Whites diagnosed with probable AD at the UT Southwestern Medical Center's Alzheimer's Disease Clinic. METHODS: The information reviewed was contained in the database of the UT Southwestern Alzheimer's Disease Center. RESULTS: In relation to Whites, Native Americans had slightly but significantly greater age at onset of symptoms (71.7 vs. 69.6 years, t = -2.08, p = .04) and equivalent cognitive scores at evaluation (Mini-Mental State Exam score = 17.4 vs. 18.5, t = 0.98, p = .33), despite significantly lower educational level (11.4 vs. 13.4 years, t = 5.63, p < .001). Native Americans were more frequently depressed on examination (22.8% vs. 9.5%, chi2 = 12, p = .001) and reported diabetes, hypertension, and heart disease significantly more often than did Whites (p < .01 for all), but their survival time after AD diagnosis was similar to that of Whites despite these comorbidities. CONCLUSIONS: With the exception of a greater prevalence of depression and cardiovascular risk factors in Native Americans than in Whites, Native Americans had a course of illness similar to that of Whites.

Fitzpatrick AL, Kuller LH, Ives DG, Lopez OL, Jagust W, Breitner JC, Jones B, Lyketsos C, Dulberg C. Incidence and prevalence of dementia in the Cardiovascular Health Study. J Am Geriatr Soc. 2004 Feb;52(2):195-204.

OBJECTIVES: To estimate the incidence and prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in the Cardiovascular Health Study (CHS) cohort. DESIGN: Longitudinal cohort study using prospectively and retrospectively collected data to evaluate dementia. SETTING: Four U.S. communities. PARTICIPANTS: There were 3,602 CHS participants, including 2,865 white and 492 African-American participants free of dementia, who completed a cranial magnetic resonance image between 1992 and 1994 and were followed for an average of 5.4 years. MEASUREMENTS: Dementia was classified by neurologist/psychiatrist committee review using neuropsychological tests, neurological examinations, medical records, physician questionnaires, and proxy/informant interviews. Demographics and apolipoprotein E (APOE) genotype were collected at baseline. Incidence by type of dementia was determined using National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD and Alzheimer's Disease Diagnostic and Treatment Center's State of California criteria for VaD. RESULTS: Classification resulted in 227 persons with prevalent dementia at entry into the study and 480 incident cases during follow-up. Incidence rates of dementia scaled to age 80 were 34.7 per 1,000 person-years for white women, 35.3 for white men, 58.8 for African-American women, and 53.0 for African-American men. Sex differences were not significant within race. Adjusted for age and education, racial differences were only of borderline significance and may have been influenced by ascertainment methodology. Rates differed substantially by educational attainment but were only significant for whites. Those with the APOE epsilon4 allele had an incidence rate at age 80 of 56.4, compared with 29.6 for those without this allele (P<.001). In whites, type-specific incidence at age 80 was 19.2 for AD versus 14.6 for VaD. These rates were 34.7 and 27.2 for African Americans. At termination of observation, women had only a slightly higher prevalence of dementia (16.0%) than men (14.7%). CONCLUSION: Sex and racial differences were not found, and VaD was higher than reported in other studies. These data provide new estimates of dementia incidence in a community sample for projection of future burden.

Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003 Aug;60(8):1119-22.

CONTEXT: Current and future estimates of Alzheimer disease (AD) are essential for public health planning. OBJECTIVE: To provide prevalence estimates of AD for the US population from 2000 through 2050. DESIGN: Alzheimer disease incidence estimates from a population-based, biracial, urban study, using a stratified random sampling design, were converted to prevalence estimates and applied to US Census Bureau estimates of US population growth. SETTING: A geographically defined community of 3 adjacent neighborhoods in Chicago, Ill, applied to the US population. PARTICIPANTS: Alzheimer disease incidence was measured in 3838 persons free of AD at baseline; 835 persons were evaluated for disease incidence.Main Outcome Measure Current and future estimates of prevalence of clinically diagnosed AD in the US population. RESULTS: In 2000, there were 4.5 million persons with AD in the US population. By 2050, this number will increase by almost 3-fold, to 13.2 million. Owing to the rapid growth of the oldest age groups of the US population, the number who are 85 years and older will more than quadruple to 8.0 million. The number who are 75 to 84 years old will double to 4.8 million, while the number who are 65 to 74 years old will remain fairly constant at 0.3 to 0.5 million. CONCLUSION: The number of persons with AD in the US population will continue to increase unless new discoveries facilitate prevention of the disease.

Suthers K, Kim JK, Crimmins E. Life expectancy with cognitive impairment in the older population of the United States. J Gerontol B Psychol Sci Soc Sci. 2003 May;58(3):S179-86.

OBJECTIVES: This article provides estimates of the prevalence of cognitive impairment by age and sex for a nationally representative sample of the U.S. population aged 70 and over. From these estimates, years of life with and without cognitive impairment are calculated. METHODS: Using data from the Assets and Health Dynamics of the Oldest Old (AHEAD) survey, the prevalence of cognitive impairment is estimated for a sample representing both the community-dwelling and institutionalized older American population. Sullivan's method is used to calculate the average number of years an elderly person can expect to live with and without cognitive impairment. RESULTS: The prevalence of moderate to severe cognitive impairment in the total U.S. population aged 70 and over is 9.5%. At age 70, the average American can expect 1.5 years with cognitive impairment. Expected length of life with cognitive impairment is longer for women than men because of their longer life expectancy. DISCUSSION: As total life expectancy continues to increase, the length of life with cognitive impairment for the American population will increase unless age-specific prevalence is reduced. There is great potential for improvement in future early treatment and diagnosis of this condition.

Bachman DL, Green RC, Benke KS, Cupples LA, Farrer LA; MIRAGE Study Group. Comparison of Alzheimer's disease risk factors in white and African American families. Neurology. 2003 Apr 22;60(8):1372-4.

The associations between alcohol, smoking, and head injury and the risk of AD in 443 African American and 2,336 white participants in the MIRAGE Study were evaluated. Alcohol had a modest protective effect in whites (odds ratio [OR] = 0.82, 95% CI = 0.68 to 0.99), with a similar trend in African Americans (OR = 0.88, 95% CI = 0.54 to 1.4). Head trauma increased the risk of AD in whites (OR = 2.3, 95% CI = 1.8 to 3.0) and African Americans (OR = 2.9, 95% CI = 1.2 to 7.0). Smoking was not associated with AD risk in whites (OR = 0.88, 95% CI = 0.73 to 1.1) or African Americans (OR = 1.0, 95% CI = 0.69 to 1.5). These risks were similar across subsets stratified by the presence or absence of the APOE epsilon4 allele.

Barker WW, Luis CA, Kashuba A, Luis M, Harwood DG, Loewenstein D, Waters C, Jimison P, Shepherd E, Sevush S, Graff-Radford N, Newland D, Todd M, Miller B, Gold M, Heilman K, Doty L, Goodman I, Robinson B, Pearl G, Dickson D, Duara R. Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank. Alzheimer Dis Assoc Disord. 2002 Oct-Dec;16(4):203-12.

Alzheimer disease (AD) is the most common dementing illness in the elderly, but there is equivocal evidence regarding the frequency of other disorders such as Lewy body disease (LBD), vascular dementia (VaD), frontotemporal dementia (FTD), and hippocampal sclerosis (HS). This ambiguity may be related to factors such as the age and gender of subjects with dementia. Therefore, the objective of this study was to calculate the relative frequencies of AD, LBD, VaD, FTD, and HS among 382 subjects with dementia from the State of Florida Brain Bank and to study the effect of age and gender on these frequencies. AD was the most frequent pathologic finding (77%), followed by LBD (26%), VaD (18%), HS (13%), and FTD (5%). Mixed pathology was common: Concomitant AD was present in 66% of LBD patients, 77% of VaD patients, and 66% of HS patients. The relative frequency of VaD increased with age, whereas the relative frequencies of FTD and LBD declined with age. Males were overrepresented among those with LBD, whereas females were overrepresented among AD subjects with onset age over 70 years. These estimates of the a priori probabilities of dementing disorders have implications for clinicians and researchers.

Kukull WA, Higdon R, Bowen JD, McCormick WC, Teri L, Schellenberg GD, van Belle G, Jolley L, Larson EB. Dementia and Alzheimer disease incidence: a prospective cohort study. Arch Neurol. 2002 Nov;59(11):1737-46.

CONTEXT: Age-specific incidence rates for dementia and Alzheimer disease (AD) are important for research and clinical practice. Incidence estimates for the United States are few and vary with the population sampled and study design; we present data that will contribute to a consensus of these rates. OBJECTIVES: To provide age-specific incidence estimates for dementia and AD and to estimate the association of sex, educational level, and apolipoprotein E genotype with onset. DESIGN: Prospective cohort study; begun in 1994 with follow-up interviews every 2 years. SETTING: Members of community-based, large health maintenance organization with demographics consistent with the surrounding base population; diagnostic evaluation by university-based study clinicians. SUBJECTS: Random sample of subjects aged 65 years or older from the base population; dementia free, nonnursing home residents. Of 5422 who were eligible, 2581 were enrolled, and 2356 had at least 1 follow-up evaluation (10 591 person-years of observation). MAIN OUTCOME MEASURE: Dementia and Alzheimer disease diagnoses were based on standard criteria. Age-specific incidence rates were calculated using a person-years approach with Poisson distribution confidence intervals. Cox proportional hazards model analysis was used to examine other factors. RESULTS: Two hundred fifteen cases of dementia and 151 cases of AD were diagnosed. Incidence rates for dementia and AD increase across the 5-year age groups; AD rates rise from 2.8 per 1000 person-years (age group, 65-69 years) to 56.1 per 1000 person-years in the older than 90-year age group. The rates nearly triple from the 75-to-79-year and 80-to-84-year age groups, but the relative increase is much less thereafter. Sex was not associated with AD onset. Educational level (>15 years vs <12 years) was associated with a decreased risk of AD; however, the association was also dependent on the baseline cognitive screening test score. CONCLUSIONS: Our dementia and AD incidence rates are consistent with recent US and European cohort studies, providing clinicians and researchers new information concerning the reproducibility of incidence estimates across settings. Increased risk was associated with age and the apolipoprotein E genotype; also with a low baseline cognitive screening test score. Educational level was inversely associated with the risk of dementia and positively associated with the baseline cognitive test score; thus, detection of AD by the screening test could also be influenced by educational level.

Zandi PP, Carlson MC, Plassman BL, Welsh-Bohmer KA, Mayer LS, Steffens DC, Breitner JC; Cache County Memory Study Investigators. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study. JAMA. 2002 Nov 6;288(17):2123-9.

CONTEXT: Previous studies have shown a sex-specific increased risk of Alzheimer disease (AD) in women older than 80 years. Basic neuroscience findings suggest that hormone replacement therapy (HRT) could reduce a woman's risk of AD. Epidemiologic findings on AD and HRT are mixed. OBJECTIVE: To examine the relationship between use of HRT and risk of AD among elderly women. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of incident dementia among 1357 men (mean age, 73.2 years) and 1889 women (mean age, 74.5 years) residing in a single county in Utah. Participants were first assessed in 1995-1997, with follow-up conducted in 1998-2000. History of women's current and former use of HRT, as well as of calcium and multivitamin supplements, was ascertained at the initial contact. MAIN OUTCOME MEASURE: Diagnosis of incident AD. RESULTS: Thirty-five men (2.6%) and 88 women (4.7%) developed AD between the initial interview and time of the follow-up (3 years). Incidence among women increased after age 80 years and exceeded the risk among men of similar age (adjusted hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.22-3.86). Women who used HRT had a reduced risk of AD (26 cases among 1066 women) compared with non-HRT users (58 cases among 800 women) (adjusted HR, 0.59; 95% CI, 0.36-0.96). Risk varied with duration of HRT use, so that a woman's sex-specific increase in risk disappeared entirely with more than 10 years of treatment (7 cases among 427 women). Adjusted HRs were 0.41 (95% CI, 0.17-0.86) for HRT users compared with nonusers and 0.77 (95% CI, 0.31-1.67) compared with men. No similar effect was seen with calcium or multivitamin use. Almost all of the HRT-related reduction in incidence reflected former use of HRT (9 cases among 490 women; adjusted HR, 0.33 [95% CI, 0.15-0.65]). There was no effect with current HRT use (17 cases among 576 women; adjusted HR, 1.08 [95% CI, 0.59-1.91]) unless duration of treatment exceeded 10 years (6 cases among 344 women; adjusted HR, 0.55 [95% CI, 0.21-1.23]). CONCLUSIONS: Prior HRT use is associated with reduced risk of AD, but there is no apparent benefit with current HRT use unless such use has exceeded 10 years.

Edland SD, Rocca WA, Petersen RC, Cha RH, Kokmen E. Dementia and Alzheimer disease incidence rates do not vary by sex in Rochester, Minn. Arch Neurol. 2002 Oct;59(10):1589-93.

BACKGROUND: Incidence rates of Alzheimer disease (AD) were higher in women than in men in several recent European and Asian studies. Cohort studies in the United States, on the other hand, have consistently reported no difference in incidence across sex. OBJECTIVE: To measure age- and sex-specific incidence rates of dementia and AD for persons aged 50 years and older residing in Rochester, Minn, during 1985 to 1989. SUBJECTS AND METHODS: Cases were ascertained through the medical records linkage system of the Rochester Epidemiology Project, which encompasses the records of all medical care providers (including outpatient clinics, hospitals, general practitioners, and nursing homes) in Rochester. Computer indices of clinical diagnoses, histologic diagnoses, and medical procedures were screened for indications of dementia. All medical records of potential cases were reviewed and abstracted by a trained nurse abstractor. A neurologist (E.K.) confirmed the presence of dementia and established a differential diagnosis of AD using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and estimated the year of onset. RESULTS: A total of 482 incident cases of dementia were identified; 356 of them (73.9%) had AD. For both dementia and AD, incidence rates increased steeply with age, and there were no consistent differences between men and women. The sex pattern for AD did not change after removing cases with silent bilateral infarcts on imaging. CONCLUSIONS: Contrary to observations from European and Asian populations, women were not at increased risk of incident AD in Rochester. Our findings, based on a medical records linkage system, corroborate findings from several other US studies that involved the direct contact of cohort members. The consistency of findings across study designs suggests that sex or sex-related exposures do not consistently play a major role in AD causation in American populations.

Miech RA, Breitner JC, Zandi PP, Khachaturian AS, Anthony JC, Mayer L. Incidence of AD may decline in the early 90s for men, later for women: The Cache County study. Neurology. 2002 Jan 22;58(2):209-18.

OBJECTIVES: To characterize the incidence of AD among the elderly population of Cache County, UT, noted for its longevity and high response rates; to explore sex differences; and to examine whether AD incidence plateaus or declines in extreme old age. METHODS: Using a multistage screening process in 1998 and 1999, and re-examining 122 individuals who had been identified 3 years earlier as cognitively compromised but not demented, the authors found 185 individuals with incident dementia (123 with AD) among 3,308 participants who contributed 10,541 person-years of observation. Adjusting for nonresponse and screening sensitivity, the authors estimated the incidence of dementia and of AD for men and women in 3-year age intervals. Multivariate discrete time survival analysis was used to examine influences of age, sex, education, and genotype at APOE, as well as interactions of these factors. RESULTS: The incidence of both dementia and AD increased almost exponentially until ages 85 to 90, but appeared to decline after age 93 for men and 97 for women. A statistical interaction between age and the presence of two APOE-epsilon 4 alleles indicated acceleration in onset of AD with this genotype; the interaction of age and one epsilon 4 suggested more modest acceleration. A statistical interaction of sex and age indicated greater incidence of AD in women than in men after age 85. CONCLUSIONS: The incidence of AD in the Cache County population increased with advancing age, but then peaked and declined among the extremely old. The presence of APOE-epsilon 4 alleles accelerated onset of AD, but did not appreciably alter lifetime incidence apparent over a span of 100 years.

Hebert LE, Beckett LA, Scherr PA, Evans DA. Annual incidence of Alzheimer disease in the United States projected to the years 2000 through 2050. Alzheimer Dis Assoc Disord. 2001 Oct-Dec;15(4):169-73.

Alzheimer disease will affect increasing numbers of people as baby boomers (persons born between 1946 and 1964) age. This work reports projections of the incidence of Alzheimer disease(AD) that will occur among older Americans in the future. Education adjusted age-specific incidence rates of clinically diagnosed probable AD were obtained from stratified random samples of residents 65 years of age and older in a geographically defined community. These rates were applied to U.S. Census Bureau projections of the total U.S. population by age and sex to estimate the number of people newly affected each year. The annual number of incident cases is expected to more than double by the midpoint of the twenty-first century: from 377,000 (95% confidence interval = 159,000-595,000) in 1995 to 959,000 (95% confidence interval = 140,000-1,778,000) in 2050. The proportion of new onset cases who are age 85 or older will increase from 40% in 1995 to 62% in 2050 when the youngest of the baby boomers will attain that age. Without progress in preventing or delaying onset of Alzheimer disease, both the number of people with Alzheimer disease and the proportion of the total population affected will increase substantially.

Neumann PJ, Araki SS, Arcelus A, Longo A, Papadopoulos G, Kosik KS, Kuntz KM, Bhattacharjya A. Measuring Alzheimer's disease progression with transition probabilities: estimates from CERAD. Neurology. 2001 Sep 25;57(6):957-64.

OBJECTIVES: To estimate annual transition probabilities (i.e., the likelihood that a patient will move from one disease stage to another in a given time period) for AD progression. Transition probabilities are estimated by disease stages (mild, moderate, severe) and settings of care (community, nursing home), accounting for differences in age, gender, and behavioral symptoms as well as the length of time a patient has been in a disease stage. Methods: Using data from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the authors employed a modified survival analysis to estimate stage-to-stage and stage-to-nursing home transition probabilities. To account for individual variability, a Cox proportional hazards model was fit to the CERAD data to estimate hazard ratios for gender, age (50 to 64, 65 to 74, and more than 75 years), and level of behavioral symptoms (low/high, according to responses to the Behavioral Rating Scale for Dementia) for each of the key stage-to-stage and stage-to-nursing home transitions. RESULTS: The transition probabilities underscore the rapid progression of patients into more severe disease stages and into nursing homes and the differences among population subgroups. In general, male gender, age under 65, and high level of behavioral symptoms were associated with higher transition probabilities to more severe disease stages. Disease progression is roughly constant as a function of the time a patient has spent in a particular stage. CONCLUSIONS: Transition probabilities provide a useful means of characterizing AD progression. Economic models of interventions for AD should consider the varied course of progression for different population subgroups, particularly those defined by high levels of behavioral symptoms.

Moceri VM, Kukull WA, Emanual I, van Belle G, Starr JR, Schellenberg GD, McCormick WC, Bowen JD, Teri L, Larson EB. Using census data and birth certificates to reconstruct the early-life socioeconomic environment and the relation to the development of Alzheimer's disease. Epidemiology. 2001 Jul;12(4):383-9.

The early-life environment and its effect on growth and maturation of children and adolescents are associated with several adult chronic diseases, including Alzheimer's disease. Because it is not feasible to collect information prospectively over the average life span, methods to reconstruct the early-life environment of the aged are necessary to evaluate these associations. In a community-based case-control study conducted in the United States, we collected U.S. census records and birth certificates to reconstruct the early-life socioeconomic environment of each elderly subject. Information was found on 82% of the available Alzheimer's disease cases (239 of 292) and 87% of the available controls (245 of 282). We investigated risk of Alzheimer's disease associated with father's occupation, parental age, household size, sibship size, and birth order. Subjects whose fathers were unskilled manual workers or laborers were at higher risk for Alzheimer's disease (odds ratio = 1.80, 95% confidence interval = 1.19--2.73). The risk of Alzheimer's disease was increased with increasing number of people in the household. We also evaluated whether subjects with the apolipoprotein epsilon 4 allele (APOE epsilon 4), a strong genetic risk factor that is not a necessary cause or a sufficient cause by itself for the development of Alzheimer's disease, were at higher risk than subjects who did not carry this allele. Among subjects with the APOE epsilon 4 allele whose fathers held lower-socioeconomic level occupations, the odds of developing Alzheimer's disease were higher (odds ratio = 2.35, 95% confidence interval = 1.07--5.16) compared with subjects without the allele (odds ratio = 1.40, 95% confidence interval = 0.78--2.52). Subjects carrying the APOE epsilon 4 allele alone have a threefold increased risk of Alzheimer's disease (odds ratio = 3.17, 95% confidence interval = 1.99--5.04). Compared with subjects with neither risk factor, subjects with both the genetic and the environmental risk factors (household size of seven or more and father's occupation being manual) had a relatively high risk of Alzheimer's disease (odds ratio = 14.8, 95% confidence interval = 4.9--46). The data suggest that APOE epsilon 4 may modify the associations between father's occupation, other early-life environmental factors, and development of Alzheimer's disease in late life.

Hebert LE, Scherr PA, McCann JJ, Beckett LA, Evans DA. Is the risk of developing Alzheimer's disease greater for women than for men? Am J Epidemiol. 2001 Jan 15;153(2):132-6.

A large proportion of people with Alzheimer's disease (AD) are women; however, it is not clear whether this is due to higher risk of disease or solely to the larger number of women alive at ages when AD is common. Beginning in 1982, two stratified random samples of people aged > or =65 years in East Boston, Massachusetts underwent detailed, structured clinical evaluation for prevalent (467 people) and incident (642 people from a cohort previously ascertained to be disease-free) probable AD. The prevalence sample was followed for mortality for up to 11 years (through December 1992). The age-specific incidence of AD did not differ significantly by sex (for men vs. women, odds ratio = 0.92; 95% confidence interval (CI): 0.51, 1.67). Controlled for age, prevalence also did not differ significantly by sex (for men vs. women, odds ratio = 1.29; 95% CI: 0.67, 2.48). The increase in risk of mortality due to AD did not vary by sex. The odds ratio for women with AD compared with women without AD was 2.07 (95% CI: 1.21, 3.56). For men, the odds ratio was 2.22 (95% CI: 1.02, 4.81). These findings suggest that the excess number of women with AD is due to the longer life expectancy of women rather than sex-specific risk factors for the disease.

Tang MX, Cross P, Andrews H, Jacobs DM, Small S, Bell K, Merchant C, Lantigua R, Costa R, Stern Y, Mayeux R. Incidence of AD in African-Americans, Caribbean Hispanics, and Caucasians in northern Manhattan. Neurology. 2001 Jan 9;56(1):49-56.

OBJECTIVE: To compare the incidence rates for AD among elderly African-American, Caribbean Hispanic, and white individuals and to determine whether coincident cerebrovascular disease contributes to the inconsistency in reported differences among ethnic groups. METHODS: This was a population-based, longitudinal study over a 7-year period in the Washington Heights and Inwood communities of New York City. Annual incidence rates for AD were calculated and compared by ethnic group, and cumulative incidence adjusted for differences in education, diabetes, cardiovascular risk factors, and stroke was calculated. RESULTS: The age-specific incidence rate for probable and possible AD was 1.3% (95% CI, 0.8 to 1.7) per person-year between the ages of 65 and 74 years, 4.0% (95% CI, 3.2 to 4.8) per person-year between ages 75 and 84 years, and 7.9% (95% CI, 5.5 to 10.5) per person-year for ages 85 and older. Compared to white individuals, the cumulative incidence of AD to age 90 years was increased twofold among African-American and Caribbean Hispanic individuals. Adjustment for differences in number of years of education, illiteracy, or a history of stroke, hypertension, heart disease, or diabetes did not change the disproportionate risks among the three ethnic groups. CONCLUSION: The incidence rate for AD was significantly higher among African-American and Caribbean Hispanic elderly individuals compared white individuals. The presence of clinically apparent cardiovascular or cerebrovascular disease did not contribute to the increased risk of disease. Because the proportion of African-American and Caribbean Hispanic individuals reaching ages 65 and older in the United States is increasing more rapidly than the proportion of white individuals, it is imperative that this disparity in health among the elderly be understood.

Kawas C, Gray S, Brookmeyer R, Fozard J, Zonderman A. Age-specific incidence rates of Alzheimer's disease: the Baltimore Longitudinal Study of Aging. Neurology. 2000 Jun 13;54(11):2072-7.

OBJECTIVE: To estimate age-specific incidence rates of AD in the Baltimore Longitudinal Study of Aging (BLSA). BACKGROUND: The BLSA is a volunteer cohort of normal subjects followed longitudinally with biennial evaluations at the Gerontology Research Center of the National Institute on Aging. METHODS: Subjects are 1236 participants (802 men, 434 women) in the BLSA with longitudinal follow-up between January 1985 and May 1998. The average length of follow-up was 7.5 years, with participants evaluated every 2 years by physical, neurologic, and neuropsychological examinations. Using Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, the authors diagnosed dementia and AD. RESULTS: The authors diagnosed 155 cases of dementia, of which 114 (74%) were AD. Incidence rates of AD increased with age from an estimated 0.08% per year (95% CI 0.00 to 0.43) in the 60 to 65 age group to an estimated 6.48% per year (95% CI 5.01 to 8.38) in the 85+ age group for men and women combined. The doubling time of incidence rates was estimated to be approximately 4.4 years and the median time of conversion from mild cognitive impairment to diagnosis of AD was estimated to be 4.4 years. There was a trend for women to have higher incidence rates than men and for fewer years of education to be associated with higher incidence rates; however, these effects were not significant. CONCLUSION: Incidence rates for AD in the BLSA are consistent with published rates in other studies. The longitudinally followed subjects of the BLSA offer a unique opportunity to prospectively investigate the antecedents of AD.

Hoyert DL, Rosenberg HM. Alzheimer's disease as a cause of death in the United States. Public Health Rep. 1997 Nov-Dec;112(6):497-505.

OBJECTIVE: To describe the scope of mortality from and trends in Alzheimer's disease, to show how Alzheimer's disease ranks as a leading cause of death, to describe a methodological change regarding ranking, and to discuss issues related to the reporting of Alzheimer's disease on death certificates. METHODS: The authors analyzed mortality data from the National Vital Statistics System. RESULTS: Alzheimer's disease has increasingly been reported as a cause of death on death certificates in the United States; however, this increase may represent a variety of factors including improved diagnosis and awareness of the disease or changes in the perception of Alzheimer's disease as a cause of death. In 1995, Alzheimer's disease was identified as the underlying cause of 20,606 deaths. Overall, Alzheimer's disease was the 14th leading cause of death in 1995; for people 65 years of age or older, it was the 8th leading cause of death. Both death rates and cause-of-death ranking differed by selected demographic variables. CONCLUSIONS: In recognition of the importance of the condition as a major public health problem, Alzheimer's disease was added to the list of causes eligible to be ranked as leading causes of death in the United States beginning with mortality data for 1994. Several issues need to be kept in mind in interpreting mortality data on Alzheimer's disease, including how diagnoses are made, how the condition is classified, and the purpose of death certificates.

Hoyert DL, Rosenberg HM. Mortality from Alzheimer's disease: an update. Natl Vital Stat Rep. 1999 Jun 30;47(20):1-8.

Alzheimer's disease is a progressive degenerative condition that has devastating implications for those afflicted. An estimated 4 million Americans, mainly elderly, have this condition, which is characterized by forgetfulness in early stages and increasingly severe debilitating symptoms as the disease progresses over what can be as long as a 20-year period. As an individual's impairment increases, informal or formal care giving becomes necessary to take care of basic needs. Annually, an estimated $80 to $100 billion dollars are spent on health care expenses or lost in wages for the persons with Alzheimer's disease or their care givers. At later stages of the disease, persons with Alzheimer's disease are bedridden and vulnerable to developing other medical conditions and dying before they would if they did not have Alzheimer's disease (1). Physicians report that Alzheimer's disease caused the death of 21,397 persons in 1996 and contributed to the death of 21,703 additional persons. This information is from death certificates completed by physicians for all deaths in the United States, a fundamental source of information on what caused death for the 2.3 million deaths in the United States. The risk of dying from Alzheimer's disease has leveled off in recent years after rapid increases in the early 1980's and subsequent slower growth in the 1990's. The trend likely reflects changes in attitudes of physicians and the public about attributing Alzheimer's disease as a cause of death as well as the availability of improved diagnostic procedures; the recent leveling in mortality trends from this condition may signal that death certificate diagnoses for Alzheimer's disease are more reliable now. Alzheimer's disease is a major cause of death, which exhibits variations by age, sex, race, and geographic area. This report provides recent mortality data on Alzheimer's disease. A previous report covers historic trends (2).

Ewbank DC. Deaths attributable to Alzheimer's disease in the United States. Am J Public Health. 1999 Jan;89(1):90-2.

OBJECTIVES: This study provided 2 estimates of the number of deaths attributable to Alzheimer's disease in the United States. METHODS: One estimate was based on data from the East Boston, Mass, study. The second was based on a simulation using population-based estimates of prevalence and separate estimates of excess death by duration of disease. RESULTS: Despite different methods and very different estimates of prevalence, these 2 methods led to very similar estimates of 173,000 and 163,000 excess deaths. CONCLUSIONS: These estimates suggest that 7.1% of all deaths in the United States in 1995 are attributable to Alzheimer's disease, placing it on a par with cerebrovascular diseases as the third leading cause of death.

Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am J Public Health. 1998 Sep;88(9):1337-42.

OBJECTIVES: The goal of this study was to project the future prevalence and incidence of Alzheimer's disease in the United States and the potential impact of interventions to delay disease onset. METHODS: The numbers of individuals in the United States with Alzheimer's disease and the numbers of newly diagnosed cases that can be expected over the next 50 years were estimated from a model that used age-specific incidence rates summarized from several epidemiological studies, US mortality rates, and US Bureau of the Census projections. RESULTS: in 1997, the prevalence of Alzheimer's disease in the United States was 2.32 million (range: 1.09 to 4.58 million); of these individuals, 68% were female. It is projected that the prevalence will nearly quadruple in the next 50 years, by which time approximately 1 in 45 Americans will be afflicted with the disease. Currently, the annual number of new incident cases in 360,000. If interventions could delay onset of the disease by 2 years, after 50 years there would be nearly 2 million fewer cases than projected; if onset could be delayed by 1 year, there would be nearly 800,000 fewer prevalent cases. CONCLUSIONS: As the US population ages, Alzheimer's disease will become an enormous public health problem. interventions that could delay disease onset even modestly would have a major public health impact.

Economics

Abstracts of selected papers

Zhu CW, Leibman C, McLaughlin T, Zbrozek AS, Scarmeas N, Albert M, Brandt J, Blacker D, Sano M, Stern Y. Patient dependence and longitudinal changes in costs of care in Alzheimer's disease. Dement Geriatr Cogn Disord. 2008;26(5):416-23. Epub 2008 Oct 22.

BACKGROUND/AIMS: To examine the incremental effect of patients' dependence on others, on cost of medical and nonmedical care, and on informal caregiving hours over time. METHODS: Data are obtained from 172 patients from the Predictors Study, a large, multicenter cohort of patients with probable Alzheimer disease (AD) followed annually for 4 years in 3 University-based AD centers in the USA. Enrollment required a modified Mini-Mental State Examination score >or=30. We examined the effects of patient dependence (measured by the Dependence Scale, DS) and function (measured by the Blessed Dementia Rating Scale, BDRS) on medical care cost, nonmedical care cost, and informal caregiving time using random effects regression models. RESULTS: A one-point increase in DS score was associated with a 5.7% increase in medical cost, a 10.5% increase in nonmedical cost, and a 4.1% increase in caregiving time. A one-point increase in BDRS score was associated with a 7.6% increase in medical cost, a 3.9% increase in nonmedical cost and an 8.7% increase in caregiving time. CONCLUSIONS: Both functional impairment and patient dependence were associated with higher costs of care and caregiving time. Measures of functional impairment and patient dependence provide unique and incremental information on the overall impact of AD on patients and their caregivers. Copyright 2008 S. Karger AG, Basel.

Frytak JR, Henk HJ, Zhao Y, Bowman L, Flynn JA, Nelson M. Health service utilization among Alzheimer's disease patients: evidence from managed care. Alzheimers Dement. 2008 Sep;4(5):361-7. Epub 2008 Apr 21.

BACKGROUND: The objective of this study was to assess the disease burden of Alzheimer's disease (AD) in a commercial managed care setting by comparing direct health care costs and adverse event outcomes between patients with AD and without AD. METHODS: The study design used eligibility, medical, and pharmacy claims data from a large, national, geographically diverse, fee-for-service U.S. managed health plan. Commercially insured patients aged 65 years and older with a pharmacy benefit with evidence of AD (n = 4,450) and a control group without AD (n = 13,650) were matched by age, gender, plan location, and length of enrollment. Adverse event outcomes, comorbid conditions, and annualized health care costs were compared. Incremental costs were calculated by using a two-part model to estimate the burden of illness; incremental cost confidence intervals were estimated by bootstrap analysis. RESULTS: Patients with AD had generally higher health care costs and higher risk of acute adverse outcomes than the control cohort. Annual adjusted total health care costs per patient were approximately $1,418 greater for the AD cohort. Patients with AD had an unadjusted fracture risk of 14.6% versus 6.2% in the matched cohort and accidental injury/falls risk of 27.4% versus 11.4%. CONCLUSIONS: Few studies have examined the disease burden of AD in commercial managed care settings. Similar to results of comparative studies with Medicare data, the disease burden is greater for patients with AD compared with a matched control cohort, with a different mix and a greater number of comorbid health care conditions partially accounting for this difference. As membership in commercial and Medicare managed care plans increases, plans will need to develop effective mechanisms to manage the health care of high-risk, high-cost patients with AD.

Kuo TC, Zhao Y, Weir S, Kramer MS, Ash AS. Implications of comorbidity on costs for patients with Alzheimer disease. Med Care. 2008 Aug;46(8):839-46.

BACKGROUND: No prior studies have used a comprehensive clinical classification system to examine the effect of differences in overall illness burden and the presence of other diseases on costs for patients with Alzheimer disease (AD) when compared with demographically matched nondemented controls. STUDY DESIGN: Of a total of 627,775 enrollees who were eligible for medical and pharmacy benefits for 2003 and 2004 in the MarketScan Medicare Supplemental and Coordination of Benefits Database, we found 25,109 AD patients. For each case, 3 demographically matched nondemented controls were selected using propensity scores. Applying the diagnostic cost groups (DCGs) model to all enrollees, 2003 diagnoses were used to estimate prospective relative risk scores (RRSs) that predict 2004 costs from all illness other than AD. RRSs were then used to control for illness burden to estimate AD's independent effect on costs. RESULTS: Compared with the control group, the AD cohort has more comorbid conditions (8.1 vs. 6.5) and higher illness burden (1.23 vs. 1.04). Individuals with AD are more likely to have mental health conditions, neurologic conditions, cognitive disorders, cerebrovascular disease, diabetes with acute complications, and injuries. Annual costs for AD patients are $3567 (34%) higher than for controls. Excess costs attributable to AD, after controlling for non-AD illness burden, are estimated at $2307 per year with outpatient pharmacy being the key driver ($1711 in excess costs). CONCLUSIONS: AD patients are sicker and more expensive than demographically matched controls. Even after adjusting for differences in illness burden, costs remain higher for AD patients.

Zhu CW, Leibman C, McLaughlin T, Scarmeas N, Albert M, Brandt J, Blacker D, Sano M, Stern Y. The effects of patient function and dependence on costs of care in Alzheimer's disease. J Am Geriatr Soc. 2008 Aug;56(8):1497-503. Epub 2008 Jul 24.

OBJECTIVES: To estimate incremental effects of patients' dependence and function on costs of care during the early stages of Alzheimer's disease (AD) and to compare strengths of their relationships with different cost components. DESIGN: Multicenter, cross-sectional, observational study. SETTING: Three university hospitals in the United States. PARTICIPANTS: One hundred seventy-nine community-living patients with probable AD, with modified Mini-Mental State Examination scores of 30 or higher. MEASUREMENTS: Patients' dependence was measured using the Dependence Scale (DS). Functional capacity was measured using the Blessed Dementia Rating Scale (BDRS). Total cost was measured by summing direct medical costs and informal costs. Direct medical costs included costs of hospitalization, outpatient treatment and procedures, assistive devices, and medications. Informal costs were estimated from time spent helping with basic and instrumental activities of daily living for up to three caregivers per patient using national average hourly earnings as wage rate. RESULTS: DS and BDRS were associated with higher total cost; a 1-point increase in DS was associated with a $1,832 increase in total cost, and a 1-point increase in BDRS was associated with a $3,333 increase. Examining component costs separately identified potential differences between DS and BDRS. A 1-point increase in BDRS was associated with a $1,406 increase in direct medical cost. A 1-point increase in DS was associated with a $1,690 increase in informal cost. CONCLUSION: Patients' dependence and function related differently to direct medical and informal cost, suggesting that measures of function and dependence provided unique information for explaining variations in cost of care for patients with AD, highlighting the value in measuring both constructs.

Zhu CW, Scarmeas N, Stavitsky K, Albert M, Brandt J, Blacker D, Sano M, Stern Y. Comparison of costs of care between patients with Alzheimer's disease and dementia with Lewy bodies. Alzheimers Dement. 2008 Jul;4(4):280-4. Epub 2008 Apr 21.

BACKGROUND: The objective of this study was to compare total costs of care and its major components for community-living patients with Alzheimer's disease (AD) or dementia with Lewy bodies (DLB). This cross-sectional analysis of baseline data from the Predictors II Study took place in three university-based AD centers in the U.S. METHODS: Community-living patients clinically diagnosed with probable AD (n = 170) or DLB (n = 25) with a modified Mini-Mental State examination (mMMS) score > or =30, equivalent to a score of approximately > or =16 on the Folstein Mini-Mental State Examination (MMSE), participated in this study. Patient and informant reported on patients' use of direct medical care, direct nonmedical care, and informal care. Patients' clinical and demographic characteristics included global cognitive status (measured by MMSE), functional capacity (measured by Blessed Dementia Rating Scale), psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, comorbidities, age, and sex. Costs were compared by using covariate matching methods. RESULTS: Unadjusted total costs and direct medical costs were not significantly different between AD and DLB patients. Compared with AD patients, unadjusted indirect costs were significantly higher and unadjusted direct nonmedical costs were significantly lower among DLB patients. After adjusting for age, sex, cognitive and functional status, differences in all cost components between DLB and AD patients were no longer statistically significant. CONCLUSIONS: Apparent cost differences were largely attributed to differences in patients' cognitive and functional status. However, the small sample size for DLB patients might have limited power to detect statistically significant differences in costs of care between these groups.

Zhao Y, Kuo TC, Weir S, Kramer MS, Ash AS. Healthcare costs and utilization for Medicare beneficiaries with Alzheimer's. BMC Health Serv Res. 2008 May 22;8:108.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder incurring significant social and economic costs. This study uses a US administrative claims database to evaluate the effect of AD on direct healthcare costs and utilization, and to identify the most common reasons for AD patients' emergency room (ER) visits and inpatient admissions. METHODS: Demographically matched cohorts age 65 and over with comprehensive medical and pharmacy claims from the 2003-2004 MEDSTAT MarketScan Medicare Supplemental and Coordination of Benefits (COB) Database were examined: 1) 25,109 individuals with an AD diagnosis or a filled prescription for an exclusively AD treatment; and 2) 75,327 matched controls. Illness burden for each person was measured using Diagnostic Cost Groups (DCGs), a comprehensive morbidity assessment system. Cost distributions and reasons for ER visits and inpatient admissions in 2004 were compared for both cohorts. Regression was used to quantify the marginal contribution of AD to health care costs and utilization, and the most common reasons for ER and inpatient admissions, using DCGs to control for overall illness burden. RESULTS: Compared with controls, the AD cohort had more co-morbid medical conditions, higher overall illness burden, and higher but less variable costs ($13,936 s. $10,369; Coefficient of variation = 181 vs. 324). Significant excess utilization was attributed to AD for inpatient services, pharmacy, ER visits, and home health care (all p < 0.05). In particular, AD patients were far more likely to be hospitalized for infections, pneumonia and falls (hip fracture, syncope, collapse). CONCLUSION: Patients with AD have significantly more co-morbid medical conditions and higher healthcare costs and utilization than demographically-matched Medicare beneficiaries. Even after adjusting for differences in co-morbidity, AD patients incur excess ER visits and inpatient admissions.

Lamb VL, Sloan FA, Nathan AS. Dementia and Medicare at life's end. Health Serv Res. 2008 Apr;43(2):714-32.

OBJECTIVE: To determine the effect of a diagnosis of Alzheimer's disease or related dementias (ADRD), and the timing of first ADRD diagnosis, on Medicare expenditures at end of life. DATA SOURCES: Monthly Medicare payment data for the 5 years before death linked to the National Long-Term Care Survey (NLTCS) for decedents between 1996 and 2000 (N=4,899). DATA EXTRACTION METHODS: Medicare payment data for the 5 years before death were used to compare 5-year and 6-month intervals of expenditures (total and six subcategories of services) for persons with and without a diagnosis of ADRD during the last 5 years of life, controlling for age, gender, race, education, comorbidities, and nursing home status. Covariate matching was used. PRINCIPAL FINDINGS: On average, ADRD diagnosis was not significantly associated with excess Medicare payments over the last 5 years of life. Regarding the timing of ADRD diagnosis, there were no significant 5-year total expenditure differences for persons diagnosed with dementia more than 1 year before death. Payment differences by 6-month intervals were highly sensitive to timing of ADRD diagnosis, with the highest differences occurring around the time of diagnosis. There were reduced, non-significant, or negative total payment differences after the initial diagnosis for those diagnosed at least 1 year before death. Only those diagnosed with ADRD in the last year of life had significantly higher Medicare payments during the last 12 months of life, primarily for acute care services. CONCLUSIONS: ADRD has a smaller impact on total Medicare expenditures than previously reported in controlled studies. The significant differences occur primarily around the time of diagnosis. Although rates of dementia are increasing per se, our results suggest that long-term (1+ year) ADRD diagnoses do not contribute to greater total Medicare costs at the end of life.

Weycker D, Taneja C, Edelsberg J, Erder MH, Schmitt FA, Setyawan J, Oster G. Cost-effectiveness of memantine in moderate-to-severe Alzheimer's disease patients receiving donepezil. Curr Med Res Opin. 2007 May;23(5):1187-97.

OBJECTIVE: The efficacy and safety of memantine in patients with moderate-to-severe Alzheimer's disease (AD) receiving stable doses of donepezil were recently demonstrated in a phase III trial. The cost-effectiveness of such therapy is unknown. RESEARCH DESIGN AND METHODS: A microsimulation model was developed to depict AD progression over time and associated clinical and economic outcomes. AD progression was measured in terms of decline in cognitive function, as assessed by the Severe Impairment Battery (SIB). At model entry, patients were assumed to have moderate-to-severe AD, to be on stable doses of donepezil, and to begin combination therapy with memantine, or continue to receive donepezil alone; duration of therapy was assumed to be 1 year. Drug efficacy was based on data from a phase III trial. Key assumptions of the model included: (1) efficacy of study drugs would extend to 1 year; (2) measures of cognitive function could be mapped to one another, as well as to global measures of disease severity; and (3) following therapy discontinuation, cognitive function would revert immediately to natural history levels. Cost-effectiveness was assessed in terms of cost (2005 US$) per quality-adjusted life-year (QALY) gained over a lifetime (3% discount rate). RESULTS: SIB scores were estimated to improve by 3.3 over 1 year from therapy with memantine plus donepezil (vs. donepezil alone). While pharmacotherapy costs were estimated to increase by $1250 during the year of memantine treatment, costs of formal and informal services were estimated to decrease by $1240 over this period and by $1493 (discounted present value) over a lifetime. Findings were sensitive to the assumed SIB score at therapy initiation; cost-effectiveness was better for patients with higher initial SIB scores (i.e., less severe disease). CONCLUSION: In patients with moderate-to-severe AD already receiving donepezil, treatment with memantine results in improved clinical outcomes and reduced total costs of care.

Stevenson DG, Huskamp HA, Keating NL, Newhouse JP. Medicare Part D and nursing home residents. J Am Geriatr Soc. 2007 Jul;55(7):1115-25.

The objective of this study was to analyze national Part D formulary data to assess adequacy of coverage across seven drug classes commonly used by nursing home residents and older people, focusing on individuals dually eligible for Medicare and Medicaid and plans in which they enroll. Focusing at the molecule level, reasonably broad coverage across drug classes and minimal prior authorization overall was found. Of nonprotected classes, 69% of plans cover at least four of five Alzheimer's medications, 76% cover at least three of four bisphosphonates, 86% cover at least three of five proton pump inhibitors, and 61% cover at least four of six 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Nevertheless, a minority of plans are less generous, and some drug formulations important to nursing home residents are covered less well. For example, 11% of plans cover only one or two of the six statins. Of protected drug classes, plans generally cover all molecules, as expected. The majority of plans require no prior authorization for covered medications in six of seven classes reviewed (excepting bisphosphonates). A minority of plans once again are more stringent. For example, 22% and 9% of Part D Plans nationally require prior authorization for all covered Alzheimer's drugs and proton pump inhibitors, respectively. Random assignment of dually eligible patients to below-benchmark plans means that some residents initially will be enrolled in these more-restrictive plans. Part D allows nursing home residents to switch plans at any time, but there are important barriers to residents' self-advocacy. Finally, it is unclear how well nursing homes and the pharmacies they work with will work across Part D plans, and vigilance will be required as the benefit proceeds.

Gorshow S. Alzheimer's disease and managed care: a convincing case for action. Manag Care Interface. 2007 Mar;20(3):26-7.

More than 4 million Americans have Alzheimer's disease (AD), and practitioners diagnose at least 400,000 news cases eachyear. Although the disease accounts for $24.6 billion in direct costs annually, it also generaites an additional $36.5 billion in indirect costs, including those attributed to lost productivityand absenteeism of caregivers for persons with AD. The increasing prevalence of AD will affect health plans with Medicare Advantage plans, as well as Medicare itself. Managed care faces challenges, both now and in the future, to deal with the effects of the disease.

Zhu CW, Scarmeas N, Torgan R, Albert M, Brandt J, Blacker D, Sano M, Stern Y. Clinical characteristics and longitudinal changes of informal cost of Alzheimer's disease in the community. J Am Geriatr Soc. 2006 Oct;54(10):1596-602.

Most estimates of the cost of informal caregiving in patients with Alzheimer's disease (AD) remain cross-sectional. Longitudinal estimates of informal caregiving hours and costs are less frequent and are from assessments covering only short periods of time. The objectives of this study were to estimate long-term trajectories of the use and cost of informal caregiving for patients with AD and the effects of patient characteristics on the use and cost of informal caregiving. The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed annually for up to 7 years in three university-based AD centers in the United States (n=170). Generalized linear mixed models were used to estimate the effects of patient characteristics on use and cost of informal caregiving. Patients' clinical characteristics included cognitive status (Mini-Mental State Examination), functional capacity (Blessed Dementia Rating Scale (BDRS)), comorbidities, psychotic symptoms, behavioral problems, depressive symptoms, and extrapyramidal signs. Results show that rates of informal care use and caregiving hours (and costs) increased substantially over time but were related differently to patients' characteristics. Use of informal care was significantly associated with worse cognition, worse function, and higher comorbidities. Conditional on receiving informal care, informal caregiving hours (and costs) were mainly associated with worse function. Each additional point on the BDRS increased informal caregiving costs 5.4%. Average annual informal cost was estimated at $25,381 per patient, increasing from $20,589 at baseline to $43,030 in Year 4.

Zhu CW, Scarmeas N, Torgan R, Albert M, Brandt J, Blacker D, Sano M, Stern Y. Longitudinal study of effects of patient characteristics on direct costs in Alzheimer disease. Neurology. 2006 Sep 26;67(6):998-1005.

OBJECTIVES: To estimate long-term trajectories of direct cost of caring for patients with Alzheimer disease (AD) and examine the effects of patients' characteristics on cost longitudinally. METHODS: The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed up annually for up to 7 years in three university-based AD centers in the United States. Random effects models estimated the effects of patients' clinical and sociodemographic characteristics on direct cost of care. Direct cost included cost associated with medical and nonmedical care. Clinical characteristics included cognitive status (measured by Mini-Mental State Examination), functional capacity (measured by Blessed Dementia Rating Scale [BDRS]), psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, and comorbidities. The model also controlled for patients' sex, age, and living arrangements. RESULTS: Total direct cost increased from approximately 9,239 dollars per patient per year at baseline, when all patients were at the early stages of the disease, to 19,925 dollars by year 4. After controlling for other variables, a one-point increase in the BDRS score increased total direct cost by 7.7%. One more comorbid condition increased total direct cost by 14.3%. Total direct cost was 20.8% lower for patients living at home compared with those living in an institutional setting. CONCLUSIONS: Total direct cost of caring for patients with Alzheimer disease increased substantially over time. Much of the cost increases were explained by patients' clinical and demographic variables. Comorbidities and functional capacity were associated with higher direct cost over time.

Zhu CW, Scarmeas N, Torgan R, Albert M, Brandt J, Blacker D, Sano M, Stern Y. Clinical features associated with costs in early AD: baseline data from the Predictors Study. Neurology. 2006 Apr 11;66(7):1021-8.

BACKGROUND: Few studies on cost of caring for patients with Alzheimer disease (AD) have simultaneously considered multiple dimensions of disease costs and detailed clinical characteristics. OBJECTIVE: To estimate empirically the incremental effects of patients' clinical characteristics on disease costs. METHODS: Data are derived from the baseline visit of 180 patients in the Predictors Study, a large, multicenter cohort of patients with probable AD followed from early stages of the disease. All patients initially lived at home, in retirement homes, or in assisted living facilities. Costs of direct medical care included hospitalizations, outpatient treatment and procedures, assistive devices, and medications. Costs of direct nonmedical care included home health aides, respite care, and adult day care. Indirect costs were measured by caregiving time. Patients' clinical characteristics included cognitive status, functional capacity, psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, comorbidities, and duration of illness. RESULTS: A 1-point increase in the Blessed Dementia Rating Scale score was associated with a $1,411 increase in direct medical costs and a $2,718 increase in unpaid caregiving costs. Direct medical costs also were $3,777 higher among subjects with depressive symptoms than among those who were not depressed. CONCLUSIONS: Medical care costs and unpaid caregiving costs relate differently to patients' clinical characteristics. Poorer functional status is associated with higher medical care costs and unpaid caregiving costs. Interventions may be particularly useful if targeted in the areas of basic and instrumental activities of daily living.

Newcomer RJ, Clay TH, Yaffe K, Covinsky KE. Mortality risk and prospective medicare expenditures for persons with dementia. J Am Geriatr Soc. 2005 Nov;53(11):2001-6.

OBJECTIVES: To determine whether an index that stratifies dementia patients into high- and low-mortality-risk groups can be effective in prospectively identifying persons with high and low expenditures. DESIGN: A mortality risk index developed for persons with dementia was used to stratify persons into groups at high and low risk of 12-month mortality. Expenditures were compiled from Medicare claims for 12 months after the predicted mortality classification. SETTING: The Medicare Alzheimer's Disease Demonstration Evaluation (MADDE) operated in eight sites across the United States. Subjects were living in a community setting at time of their mortality risk classification. PARTICIPANTS: Participants (N=2,255) were volunteer enrollees in MADDE; all had a diagnosis of irreversible dementia and two or more limitations in activities of daily living (ADLs). MEASUREMENTS: Outcomes were Medicare Part A expenditures. Risk factors included age, sex, ADL limitations, selected chronic conditions, prior year hospital stays, and relationship to caregiver. RESULTS: Patients predicted as at high risk of death had higher average monthly Medicare expenditures than those predicted to be at low risk of death. At the 50th sensitivity percentile for mortality, differences in average expenditures exceeded 700 dollars per month. CONCLUSION: It is not known whether it is possible to achieve reductions in expenditures for patients with advanced dementia at high risk of mortality, but study findings support consideration of an advanced illness model that would attempt to generate acute services savings and use these savings for palliative services that might improve patients' and caregivers' quality of life.

Fillit H, Hill J. Economics of dementia and pharmacoeconomics of dementia therapy. Am J Geriatr Pharmacother. 2005 Mar;3(1):39-49.

BACKGROUND: The economic impact of dementia is not well appreciated, even though Alzheimer's disease and related dementias were the third most expensive health condition in the United States in 2000. In 1997, the cost of managing patients with Alzheimer's disease and other dementias was estimated at US dollar 100 billion. Direct medical costs are compounded by indirect costs of care, including unpaid care and loss of earnings. OBJECTIVE: The aim of this review was to examine studies of the economic impact of approved treatments for dementia therapy. METHODS: Searches of the MEDLINE database were conducted to identify prospective, randomized trials and retrospective or modeling studies of the economic impact of dementia medications, as well as analyses of managed care data (years 1996-2004; English language; search terms: dementia or Alzheimer's cross-referenced with economic or costs). RESULTS: Only 3 studies directly examined the economic effects of dementia therapy. Two of these demonstrated economic benefits of treatment, whereas the third study concluded that there were no benefits; however, the conclusions of the latter study may have been weakened by such factors as the high rate of attrition and biased selection of study participants. Modeling studies and analyses of managed care data also indicate economic benefits from approved treatments. CONCLUSIONS: Therapies that are efficacious early in the disease can postpone the progression of dementia to more severe stages and may offer economic benefit to patients' families, caregivers, and society.

Harrow BS, Mahoney DF, Mendelsohn AB, Ory MG, Coon DW, Belle SH, Nichols LO. Variation in cost of informal caregiving and formal-service use for people with Alzheimer's disease. Am J Alzheimers Dis Other Demen. 2004 Sep-Oct;19(5):299-308.

This study used a geographically diverse sample to estimate the total cost of informal care and formal services for community-residing Alzheimer's disease (AD) care recipients. Baseline data were used for 1200 family caregivers from the Resources for Enhancing Alzheimer's Caregiver Health (REACH) study, a multisite intervention trial. The replacement-wage-rate approach estimated informal cost. Formal services were assigned a cost based on secondary sources. Annual cost per care recipient amounted to 23,436 dollars for informal care and 8064 dollars for formal services. Variation in informal cost was almost entirely due to instrumental activities of daily living (IADLs) assistance. Cross-site differences in cost persisted after controlling for caregiver and care-recipient characteristics. Geographic variation may suggest regional preferences or ethnic/cultural values. Further study is needed to determine whether this reflects differences in access or availability or how including a control group for care recipients with nondementia diagnoses might have affected these findings.

Marin D, Amaya K, Casciano R, Puder KL, Casciano J, Chang S, Snyder EH, Cheng I, Cuccia AJ. Impact of rivastigmine on costs and on time spent in caregiving for families of patients with Alzheimer's disease. Int Psychogeriatr. 2003 Dec;15(4):385-98.

BACKGROUND: Alzheimer's disease (AD) places a significant burden on health care systems worldwide. As new treatments are developed, their cost-effectiveness is often assessed to help health care professionals make informed decisions. In addition to the more common practice of assessing direct medical costs, indirect costs, including time spent in caregiving, should be evaluated. METHODS: This study examined the potential effects of the dual cholinesterase inhibitor rivastigmine (Exelon) on caregivers of patients with AD. Results from two 26-week, placebo-controlled trials have demonstrated the clinically relevant and statistically significant efficacy of rivastigmine (6-12 mg/day) compared to placebo, on cognition, activities of daily living, and global functioning. By delaying progression of AD, significant savings in caregiver burden are anticipated, as measured by time spent caregiving and its related costs. Data collected in a prospective, observational study of AD patients and their caregivers were used to establish the relationship between disease severity (based on Mini-Mental State Examination [MMSE] score) and time spent caregiving (according to the 5-item Caregivers Activity Survey score). A significant correlation was observed between the two scores (N = 43, r = -.56, p < .0001), demonstrating that more time for supervision from caregivers is required as the disease progresses. This finding was used to estimate the reduced caregiver burden resulting from the delay in disease progression that was demonstrated with use of rivastigmine. RESULTS: Over a 2-year period, the reduction in time spent in caregiving reached 691 hours for caregivers of patients with mild AD (MMSE score 21-30), resulting in a total savings of approximately 11,253 dollars. Treatment of patients with moderately severe AD was also evaluated. The trend was similar but the impact was less, suggesting an economic benefit to early therapy. CONCLUSION: Early diagnosis and a pharmacologic intervention that allows the patients to remain at home longer by delaying disease progression would have a beneficial impact on patients, caregivers, and payers, and should therefore be encouraged through initiatives designed to identify and treat patients early in the course of disease.

Murman DL, Kuo SB, Powell MC, Colenda CC. The impact of parkinsonism on costs of care in patients with AD and dementia with Lewy bodies. Neurology. 2003 Oct 14;61(7):944-9.

OBJECTIVE: To compare the annual direct costs for patients with Alzheimer's disease (AD) and no parkinsonism (AD), patients with AD and parkinsonism (AD/P), and patients with dementia with Lewy bodies (DLB). For the entire sample, the authors examined the incremental costs associated with increasing parkinsonism. METHODS: Cross-sectional comparisons of 1 year of direct costs were done. Fifteen patients met criteria for DLB, and 133 met criteria for probable AD, of whom 39 had signs of parkinsonism and 94 did not. Patients' caregivers reported on the patient's use of health care services, receipt of unpaid care, and comorbid medical conditions. Severity of cognitive impairment and parkinsonism were determined during patient examinations. Costs were estimated by multiplying utilization data by a unit cost for each type of care. Costs were compared after adjustment for covariates using multiple regression equations. RESULTS: After adjusting for important covariates, patients with AD/P or DLB had significantly higher annual direct costs than patients with AD. The average adjusted increases in costs above the AD baseline costs were 7,119 dollars (AD/P) and 13,754 dollars (DLB) for formal direct costs and 7,394 dollars (AD/P) and 19,564 dollars (DLB) for total direct costs. Models for the entire sample estimated that a 1-point increase in a parkinsonism scale would result in an annual increase of 784 dollars in formal costs and 827 dollars in total costs of care. CONCLUSIONS: Patients with Alzheimer's disease and parkinsonism or dementia with Lewy bodies have significantly higher formal and total direct costs of care than patients with Alzheimer's disease. Signs of parkinsonism in patients with degenerative dementias are significant independent predictors of costs of care.

Migliaccio-Walle K, Getsios D, Caro JJ, Ishak KJ, O'Brien JA, Papadopoulos G; AHEAD Study Group. Economic evaluation of galantamine in the treatment of mild to moderate Alzheimer's disease in the United States. Clin Ther. 2003 Jun;25(6):1806-25.

BACKGROUND: Alzheimer's disease (AD) is estimated to affect up to 11% of those aged > or =65 years in the United States, and the number of patients with AD is predicted to increase over the next few decades as the population ages. The substantial social and economic burden associated with AD is well established, with the cost of management increasing as the disease progresses. OBJECTIVE: The aim of this study was to evaluate the economic impact of galantamine 16 and 24 mg/d relative to no pharmacologic treatment in the management of mild to moderate AD in the United States based on the concept of need for full-time care (FTC). METHODS: Calculations were made using the Assessment of Health Economics in Alzheimer's Disease model, which applies predictive equations to estimate the need for FTC and the associated costs. The predictive equations were developed from longitudinal data on patients with AD. Inputs to the equations were derived by analyzing the data from 2 randomized, placebo-controlled, galantamine clinical trials. Resource use (from a payer perspective) was estimated from US clinical trial data, and costs were estimated from several US databases. Analyses were carried out over 10 years, and costs and benefits were discounted at 3%. RESULTS: In the base case, 3.9 to 4.6 patients need to start treatment with galantamine to avoid 1 year of FTC, depending on dose. Treated patients spent 7% to 8% more time pre-FTC and 12% to 14% less time requiring FTC, resulting in savings of 2408 to 3601 US dollars. Time horizons below 3 years, very high discontinuation rates, or increased survival with galantamine reversed the savings. Conversely, limiting treatment to responders delayed FTC by 6 to 7 months, with savings of approximately 9097 to 11,578 US dollars. CONCLUSIONS: These results suggest that use of galantamine in patients with AD in the United States could reduce the use of costly resources such as formal home care and nursing homes, leading to cost savings over time.

Leifer BP. Early diagnosis of Alzheimer's disease: clinical and economic benefits. J Am Geriatr Soc. 2003 May;51(5 Suppl Dementia):S281-8.

An estimated four million individuals in the United States have Alzheimer's disease (AD). This number is expected to more than triple by mid-century. Primary care physicians have a key role in evaluating older patients for early signs of dementia and in initiating treatment that can significantly retard its progression over the maximum period of time. That role and its challenges will inevitably grow along with the expected increase in the population aged 65 and older. The tendency for physicians to dismiss memory complaints as normal aging must be replaced by awareness of the need to assess and possibly intervene. Early intervention is the optimal strategy, not only because the patient's level of function will be preserved for a longer period, but also because community-dwelling patients with AD incur less societal cost than those who require long-term institutional placement. Institutionalization contributes heavily to the annual cost of care for AD in the United States, which is estimated to be 100 billion dollars annually.

Sloan FA, Taylor DH Jr. Effect of Alzheimer disease on the cost of treating other diseases. Alzheimer Dis Assoc Disord. 2002 Jul-Sep;16(3):137-43.

The authors' objective is to determine the effect of diagnosed Alzheimer disease (AD) on cost to Medicare of treating other diseases. Using the 1994 National Long-Term Care Survey merged with Medicare claims and death data, the authors assessed the relative cost to Medicare of covering beneficiaries over 1994-1995 with diagnosed AD relative to other elderly population. They focused on hospitalizations during 1994-1995 for hip fracture, stroke, coronary heart disease, congestive heart failure, and pneumonia. The authors determined whether differences in Medicare payments by AD status mainly reflected differences in rates of occurrence of hospitalizations for the five primary diagnoses, other primary diagnoses, or death during 1994-1995 or in spending given the adverse events. During 1994-1995, an average of $15,700 was spent by Medicare, per person, for those with diagnosed AD, nearly twice the amount spent on others. The difference in Medicare payments was attributable to more adverse events occurring to AD group. Such persons had higher death rates than other elderly population (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.07-1.62), higher hospitalization rates for hip fracture (OR, 1.96; 95% CI, 1.34-2.87), stroke (OR, 1.71; 95% CI, 1.10-2.68), pneumonia (OR, 1.46; 95% CI, 1.07-1.99), and for other reasons than the five conditions (OR, 1.65; 95% CI, 1.38-1.98), but they also had lower hospitalization rates for the cardiac diseases. There were no differences in Medicare payments according to AD diagnosis, controlling for frequency of deaths, hospitalizations, and other factors. Persons with diagnosed AD cost Medicare more because of more adverse health events rather than in intensity of care, given event occurrence.

Albert SM, Glied S, Andrews H, Stern Y, Mayeux R. Primary care expenditures before the onset of Alzheimer's disease. Neurology. 2002 Aug 27;59(4):573-8.

OBJECTIVE: To investigate primary care expenditures in the period before diagnosis of AD. METHODS: In a population-based sample of Medicare enrollees in New York City, person-level 1996 Medicare claims, summed over primary care encounters, were examined for people who developed AD in 1997 to 1998 and those who did not. RESULTS: People who developed AD were more likely to use Medicare outpatient and ambulatory care 1 to 2 years before diagnosis. Compared with respondents who did not develop AD, the excess cost for men was $1,167 (85% higher) and for women $239 (26% higher). Among elderly people > or = 75 years in the United States, the prodromal period of AD was associated with an excess Medicare-based primary care cost of $128.5 to $194.7 million. CONCLUSION: In addition to huge costs associated with AD after diagnosis, prediagnosis costs are an unrecognized source of expenditures related to the disease.

Fillit H, Hill JW, Futterman R. Health care utilization and costs of Alzheimer's disease: the role of co-morbid conditions, disease stage, and pharmacotherapy. Fam Med. 2002 Jul-Aug;34(7):528-35.

BACKGROUND AND OBJECTIVES: Studies on the relationship between Alzheimer's disease (AD) and health care costs have yielded conflicting results. This study analyzed the relationship between co-morbid conditions and health care utilization and costs for patients with AD and estimated costs by stage of disease and receipt of pharmacotherapy. METHODS: We conducted a retrospective analysis of administrative data for 1,366 patients with AD and 13,660 age-gender matched controls enrolled in a large Medicare managed care organization (MCO). Co-morbid conditions were based on the diagnostic classifications from the Charlson co-morbidity index. Health care costs and utilization for MCO-covered services for cases were compared to controls. We used presence of complications of AD associated with later-stage disease to classify patients as having earlier- or later-stage AD. RESULTS: After controlling for co-morbid conditions, age, and gender, annual costs were $3,805 higher for AD patients, resulting in excess costs of $5 million to the MCO. For seven of the 10 most prevalent co-morbidities for AD patients, adjusted costs were higher for AD patients compared with controls with the same condition. Higher costs were attributable to higher inpatient and skilled nursing facility costs. Costs for patients classified as earlier-stage AD were 44% higher than controls and significantly higher for eight of 10 co-morbid conditions when compared with controls with the same conditions. Costs for AD patients receiving treatment by a cholinesterase inhibitor were $2,408 lower than AD patients not receiving therapy. CONCLUSIONS: Utilization and costs for patients with AD were higher compared to controls and were substantially higher for patients with both AD and co-morbid diseases commonly targeted for disease management. Earlier-stage AD and receipt of pharmacotherapy were associated with lower costs. These findings indicate that better treatment and care management of AD could reduce the costs of co-morbid illnesses commonly suffered by AD patients.

Small GW, McDonnell DD, Brooks RL, Papadopoulos G. The impact of symptom severity on the cost of Alzheimer's disease. J Am Geriatr Soc. 2002 Feb;50(2):321-7.

OBJECTIVES: ITo examine the economic impact of Alzheimer's disease (AD) as the disease progresses on patients' medical costs and caregivers' productivity. DESIGN: A 12-page, self-administered mail survey, fielded in November 1999. SETTING: Households with AD caregivers, selected from a nationwide (U.S.) consumer database. PARTICIPANTS: One thousand seven hundred fifteen caregivers of noninstitutionalized AD patients. MEASUREMENTS: Disease progression was measured using a scale of symptom frequency and measures of instrumental and physical functioning. Cost components included hospital days, physician visits, and emergency room visits. Lost productivity was assessed using hours per week that caregivers provided care and the number of days that they missed from work because of caregiving. RESULTS: The direct costs of caring for AD patients for 6 months totaled $3,129, whereas the indirect costs were $26,080. Patients with more-frequent symptoms used all healthcare resources, including the hospital, emergency room, and physicians, more often than those with less-frequent symptoms. Those with lower levels of physical and instrumental functioning also used the hospital and physicians more often than those with higher levels of physical and instrumental functioning. Caregivers of these more severely impaired patients spent more hours providing care and reported missing more work than those caring for higher-functioning patients. These relationships remained after controlling for potentially confounding factors. CONCLUSIONS: This large study of patients at all stages of AD shows that the direct and indirect costs of AD are considerably lower for patients with fewer symptoms. Longitudinal studies will determine the impact on the overall cost of care of interventions that reduce symptoms and maintain patients at earlier stages of the disease.

Hill JW, Futterman R, Mastey V, Fillit H. The effect of donepezil therapy on health costs in a Medicare managed care plan. Manag Care Interface. 2002 Mar;15(3):63-70.

The objective of this study was to estimate the ramifications of donepezil use on the health care costs of a large Medicare managed care plan. Patients with a diagnosis of Alzheimer's disease or related dementia were identified from the claims-and-encounter records of the plan. Costs for 204 patients identified as having Alzheimer's disease and who were receiving donepezil were compared with a control group of 204 patients with Alzheimer's disease who had matching characteristics, but who were not receiving therapy. After controlling for age, gender, pharmacy benefits, comorbid conditions, and complications of dementia, annual costs for medical services and prescription drugs were found to be $3,891 lower for the study group. Costs were $4,192 lower for patients receiving longer-term therapy (> or = 270 day supply of donepezil) and $3,579 lower for patients receiving shorter-term therapy when compared with controls. By improving cognitive and daily functioning, donepezil may lower costs by improving medical management.

Hill JW, Futterman R, Duttagupta S, Mastey V, Lloyd JR, Fillit H. Alzheimer's disease and related dementias increase costs of comorbidities in managed Medicare. Neurology. 2002 Jan 8;58(1):62-70.

OBJECTIVES: To analyze the relationship between comorbid conditions and costs for patients with AD and related dementias (ADRD) in a Medicare managed care organization (MCO). To derive implications for improving management of patients with ADRD. METHODS: Retrospective analysis was carried out on administrative data for 3,934 patients with ADRD and 19,300 age/sex-matched control subjects enrolled in a large Medicare MCO. Patients with ADRD were identified from diagnoses on medical claims and encounter data for a 2-year period. Control subjects were selected from health plan members without dementia. Comorbid conditions were based on the diagnostic classifications from the Charlson comorbidity index. Health care costs and utilization for MCO-covered services for cases were compared with those of control subjects. RESULTS: Prevalence of ADRD was 4.4%, substantially higher than reported in previous studies of Medicare managed care and similar to population-based estimates. After controlling for comorbid conditions, age, and sex, annual costs were $4,134 higher for ADRD patients, resulting in excess costs of $16 million to the MCO. For the 10 most prevalent comorbidities in ADRD patients, adjusted costs were higher for ADRD patients compared with control subjects with the same condition. Higher costs were attributable to higher inpatient and skilled nursing facility utilization. CONCLUSIONS: In this study, prevalence rates for ADRD mirrored population estimates. Costs for patients with ADRD in this Medicare MCO varied considerably by comorbid condition and were substantially higher for patients with both AD and comorbid diseases commonly targeted for disease management, indicating that AD increases costs through effects on the management of comorbid illnesses. These findings indicate that better treatment and care management of AD could reduce the costs of comorbid illnesses commonly experienced by the frail elderly.

DeKosky ST, Orgogozo JM. Alzheimer disease: diagnosis, costs, and dimensions of treatment. Alzheimer Dis Assoc Disord. 2001 Aug;15 Suppl 1:S3-7.

Alzheimer disease (AD) is the most frequent cause of dementia in developed Western countries. Over time, affected patients invariably develop cognitive and functional decline, and most develop early or later behavioral disturbances. Declining cognitive and functional abilities contribute to loss of independent living and feelings of denial, confusion, fear and guilt until, finally, the patient loses most abilities to think, move, speak, or perceive. As patients' dependency on assistance increases, the level of caregiver strain rises. The caregiver may develop feelings of anger, grief, loneliness and resentment, and the health and well-being of most caregivers are often affected. Approximately 3-4 million people currently have AD in the USA, at an annual cost of up to US$100 billion, and the disease is expected to reach epidemic proportions by 2020. To achieve a clinically relevant, long-term outcome, pharmacotherapy must have sustained favorable effects on cognitive, functional and behavioral symptoms of AD. Slowing the development of these features of the disease will mean a long-term improvement in quality of life for patients and caregivers. Postponing the emergence of behavioral symptoms would bring about direct beneficial effects on patients with AD and their families, help delay long-term care placement and lower costs.

Taylor DH Jr, Schenkman M, Zhou J, Sloan FA. The relative effect of Alzheimer's disease and related dementias, disability, and comorbidities on cost of care for elderly persons. J Gerontol B Psychol Sci Soc Sci. 2001 Sep;56(5):S285-93.

OBJECTIVES: Our primary objectives were (a) to determine the relative impact of Alzheimer's disease and related dementias (ADRD), disability, and common comorbid health conditions on the cost of caring for community-dwelling elderly person and (b) to determine whether ADRD serves as an effect modifier for the effect of disability and common comorbidities on costs. METHODS: Participants were drawn from community respondents to the 1994 National Long Term Care Survey. The authors compared total cost of caring for persons without ADRD with that of those who had moderate and severe ADRD. Using regression analysis, the author identified the adjusted effect of ADRD, limitations in activities of daily living (ADLs), and common comorbidities on total costs. RESULTS: Persons with severe ADRD had higher median total costs ($10,234) than did persons with moderate ADRD ($4,318) and those without ADRD ($2,268, p <.001). However, disability measured by ADL limitations was a more important predictor of total cost than was ADRD status in both stratified and multivariate analyses. Comorbidities such as heart attack, stroke, and chronic obstructive pulmonary disease also increased costs. Severe ADRD was an effect modifier for ADL limitations, increasing the positive impact of disability on total costs among persons with severe ADRD, but not for comorbidities. DISCUSSION: Disability, severe ADRD, and comorbidity all had independent effects that increased total costs. Thus, any risk adjustment procedure should account for disability and comorbidity and not just ADRD status.

Rice DP, Fillit HM, Max W, Knopman DS, Lloyd JR, Duttagupta S. Prevalence, costs, and treatment of Alzheimer's disease and related dementia: a managed care perspective. Am J Manag Care. 2001 Aug;7(8):809-18.

BACKGROUND: The number of patients with Alzheimer's disease (AD) and related dementia treated in managed care organizations (MCOs) is increasing, and this trend is expected to continue. Therefore, it is critical that MCOs develop disease management strategies for this population. OBJECTIVE: To review the literature on the prevalence, costs, and treatment of AD and related dementia. STUDY DESIGN: Review of published articles from MEDLINE and peer-reviewed journals. RESULTS: Prevalence of AD and related dementia is approximately 5.7% among those aged 65 and older. Prevalence data from claims-based studies of AD in managed care are lower, ranging from 0.55% to 0.83%. Costs for formal care average $27,672 per patient annually, with long-term care being the most costly component. Annual costs for informal care are estimated to be $10,400 to $34,517 per patient. Additional costs associated with AD include lost wages and productivity of patients and caregivers and costs associated with increased morbidity of caregivers. Donepezil treatment is well tolerated and has been extensively tested and evaluated in clinical settings. Early diagnosis and treatment of AD with donepezil has been shown to slow cognitive decline in AD. Although study findings regarding the cost offsets of donepezil-treated patients to date are mixed, there is a growing body of evidence to support the inclusion of this and other therapies into an MCO's AD treatment armamentarium. CONCLUSIONS: It is unlikely that MCOs will escape the increased prevalence and costs associated with AD. Opportunities exist through patient management programs targeted toward early diagnosis, effective use of medications, control of comorbidities, and patient and family support to partially offset these costs while providing quality patient care.

Fox PJ, Kohatsu N, Max W, Arnsberger P. Estimating the costs of caring for people with Alzheimer disease in California: 2000-2040. J Public Health Policy. 2001;22(1):88-97.

The costs of caring for people with Alzheimer disease (AD) in California are estimated using data from a study of the costs of caring for community-resident and institutionalized people with AD, combined will prevalence and population projections. Costs for community-resident patients will increase 83 percent in the period 2000 ($23.4 billion) to 2020 ($42.8 billion), and will grow an additional 59 percent from 2020 to 2040 ($68.1 billion). Costs for AD patients in institutions will increase 84 percent from 2000 ($2.5 billion) to 2020 ($4.6 billion), and will grow an additional 61 percent from 2020 to 2040 ($7.4 billion), assuming the supply of nursing home beds meets projected demand. Total costs of caring for AD patients will nearly triple between 2000 and 2040. The rapid aging of the U.S. population makes more aggressive societal action necessary if the personal and societal burden of Alzheimer's disease is to be reduced in the future.

Martin BC, Ricci JF, Kotzan JA, Lang K, Menzin J. The net cost of Alzheimer disease and related dementia: a population-based study of Georgia Medicaid recipients. Alzheimer Dis Assoc Disord. 2000 Jul-Sep;14(3):151-9.

The objective of this study was to estimate the direct medical cost of Alzheimer disease (AD) and related dementia to the Georgia Medicaid program. A retrospective, cross-sectional, matched control group design was used. AD cases 50 years of age and older were identified by using International Classification of Diseases (9th edition, Clinical Modification) diagnosis codes from 1994 Georgia Medicaid administrative claims files. For every case, three age- and gender-matched non-AD controls were selected. Differences in average recipient Medicaid expenditures between cases and controls were estimated using weighted least squares regression analysis, adjusting for age, gender, race, Charlson comorbidity index, Medicare eligibility, and months of Medicaid eligibility. A total of 8,671 AD cases were identified (prevalence, 4.4%). The average adjusted annual Medicaid expenditure per AD recipient was $14,492 (U.S.). The net (i.e., excess) average annual Medicaid cost per AD recipient (i.e., the difference in adjusted mean expenditures between cases and controls) was estimated to be approximately $8,200. Excessive nursing home expenditures accounted for most of the additional cost of treating dementia (> 85%), although inpatient hospital, physician, outpatient, and prescription drug expenditures also were higher among patients with AD. Based on these estimates, Georgia Medicaid is projected to spend almost $70 million annually for AD and related dementia. The excessive cost attributable to AD poses a significant burden to the Georgia Medicaid program.

Taylor DH Jr, Sloan FA. How much do persons with Alzheimer's disease cost Medicare? J Am Geriatr Soc. 2000 Jun;48(6):639-46.

BACKGROUND: Medicare claims are increasingly being used to identify persons with chronic diseases such as Alzheimer's disease (AD) for the purpose of determining the cost to Medicare of caring for such persons. Past work has been limited by the use of only 1 or 2 years of claims data to identify cases, leading to worries that this might lead to an undercount of prevalent cases and bias cost findings. OBJECTIVES: To analyze the average total cost to the Medicare program in 1994 of persons with a claims-based diagnosis of AD, using a 12-year period of claims history to identify prevalent cases, and to investigate the effect on cost of time since diagnosis. DESIGN: A cross-sectional design with a 12-year retrospective period to identify persons with AD. SETTING: Medical care practices, hospitals, and other providers of services to Medicare beneficiaries in the US in 1994. SUBJECTS: Respondents to the screener (n = 10,858) and community (5429) and institutional (n = 1341) questionnaire of the 1994 National Long Term Care Survey, with and without a claims-based diagnosis of AD. MEASUREMENTS: Average total cost to Medicare in 1994, measured as the actual amount Medicare paid for inpatient, outpatient, home health, skilled nursing facility, hospice, and Part B services, including payments to physicians, and other items such as durable medical equipment. We also measured disability in a variety of ways, including cognition, activity limitations, and residence in a nursing home. RESULTS: The average total cost to Medicare of persons with a claims-based diagnosis of AD was $6021 versus $2310 (P < .001) for persons without a diagnosis. When adjusting for patient characteristics, the ratio of cost between persons with AD and those without was reduced to about 1.6 to 1. Time since diagnosis was an important predictor of average total cost in 1994, with each additional year since diagnosis resulting in a $248 (P = .04) decrease in total cost (about 10% of the total sample mean cost of $2426). There was mixed evidence that persons with a diagnosis of AD incurred less cost than otherwise similarly disabled Medicare beneficiaries. CONCLUSIONS: Time since diagnosis with AD is an important predictor of cost and one that should be explicitly included in any rate-setting formula. Expanding the period used to identify cases resulted in an increase in the unadjusted ratio of cost of a Medicare beneficiary with AD relative to one without primarily because our control group costs are lower compared with those of past work.

Leon J, Neumann PJ. The cost of Alzheimer's disease in managed care: a cross-sectional study. Am J Manag Care. 1999 Jul;5(7):867-77.

BACKGROUND: The number of people with Alzheimer's disease (AD) is expected to grow as the US population ages. Given the increasing enrollment in managed care organizations, growth in the number of managed care patients with AD is a certainty. To our knowledge, no study to date has focused on the cost of care of community-dwelling AD patients receiving care through a health maintenance organization (HMO) system. METHODS: One hundred and fifty patients were recruited from 4 managed care sites from July through December 1996. Staff at each site clinically confirmed patients' AD diagnosis, AD severity, and ascertained patients' comorbidities. Demographic, quality of life, and service utilization data were collected from proxy respondents. Costs of hospitalization, medications, doctor visits (formal costs), and caregiver assistance (informal costs) were analyzed separately. RESULTS: The average total (formal and informal) per-patient costs in the 4 settings in 1996 were $18,804. Costs increased with cognitive impairment. For patients with mild, moderate, and severe AD, annual total costs were $14,904, $19,272, and $25,860, respectively. Annual direct costs were $5520, $7044 and $10,992, respectively. CONCLUSION: Across all severity levels, we calculated a total annual cost of $8.8 billion for managed care enrollees older than 65 years in the United States. We did not estimate these costs for the population younger than 65 years because of the variability in AD prevalence estimates. Due to the increased costs for patients with more severe AD, interventions that would reverse or delay progression may result in significant cost savings.

Menzin J, Lang K, Friedman M, Neumann P, Cummings JL. The economic cost of Alzheimer's disease and related dementias to the California Medicaid program ("Medi-Cal") in 1995. Am J Geriatr Psychiatry. 1999 Fall;7(4):300-8.

Although state Medicaid programs may bear a large portion of the costs of Alzheimer's disease (AD), current information on spending is not available. Using a health insurance claims database for a 10% random sample of California Medicaid ("Medi-Cal") recipients 60+ years of age, the authors estimated the excess cost of AD to Medi-Cal in 1995 as the difference in expenditures between an AD cohort (those with AD or related dementias) and an age- and sex-matched cohort without AD. Among 62,450 recipients, 2,575 (4.1%) were found to have AD or related dementias, and their average payments were approximately $7,700 higher (P<0.01) than those for the comparison group. These estimates suggest that Medi-Cal spends about $200 million on AD and related dementias annually, a burden that represents nearly 10% of state spending on elderly patients.

Gutterman EM, Markowitz JS, Lewis B, Fillit H. Cost of Alzheimer's disease and related dementia in managed-medicare. J Am Geriatr Soc. 1999 Sep;47(9):1065-71.

BACKGROUND: Managed care organizations (MCOs) will have increased responsibility for the care of large numbers of persons with dementia. There are, however, few studies that inform about decisions of healthcare utilization and expenditures for individuals with dementia in managed care. OBJECTIVES: To examine in a large MCO whether people diagnosed with dementia have higher healthcare utilization and costs than enrollees without dementia. DESIGN: A retrospective study of medical and prescription claims. SETTING: An MCO covering more than 80,000 Medicare enrollees in four geographical locales between January 1, 1996, and March 31, 1998. SUBJECTS: There were 677 paired cases with and without dementia. Controls were selected randomly and matched to cases on age, gender, and region. MEASUREMENTS: Summed total costs and number of claims accrued during the study period, as well as a breakdown of costs and claims with respect to place of service, were annualized and adjusted for age, gender, and comorbid conditions. Costs and claims were broken down by place of service. RESULTS: Dementia prevalence was 0.83%. Mean total costs were 1.5 times higher for patients with dementia relative to controls ($13,487 vs $9,276, P < .001) when annualized and adjusted for level of comorbidity. Almost 75% of the higher costs among cases were linked to inpatient expenses. CONCLUSIONS: Higher costs for individuals with dementia and disproportionate inpatient costs in this MCO parallel patterns among Medicare enrollees in fee-for-service. The high prevalence of dementia among the oldest old coupled with the high costs of dementia care create very significant clinical and financial incentives for managed care plans to improve the care of members suffering from dementia.

Leon J, Cheng CK, Neumann PJ. Alzheimer's disease care: costs and potential savings. Health Aff (Millwood). 1998 Nov-Dec;17(6):206-16.

A cross-sectional study of 679 Alzheimer's disease patients from thirteen sites in nine states provides a unique opportunity to estimate costs of Alzheimer's disease care by disease stage and care setting and to explore potential areas of cost savings. In 1996 annual costs of caring for patients with mild, moderate, and severe Alzheimer's disease were $18,408, $30,096, and $36,132, respectively. Monthly savings of $2,029 in formal services are possible if disease progression can be slowed. Annual institutional cost savings of $9,132 also are achievable if alternative residential settings are used.

Schumock GT. Economic considerations in the treatment and management of Alzheimer's disease. Am J Health Syst Pharm. 1998 Nov 1;55 Suppl 2:S17-21.

Cost issues and formal economic evaluations of treatment for Alzheimer's disease (AD) are reviewed. The annual cost of AD in the United States is estimated to be $100 billion. Each case of AD is associated with total costs of up to $195,000, with a substantial portion of this attributable to lost patient and caregiver productivity and to family out-of-pocket expenses. Only a few studies have evaluated the economic impact of therapeutic interventions in AD. In one study of tacrine, dosages greater than 80 mg/day significantly delayed nursing-home placement. In another study, treatment that improved cognitive deficits significantly reduced the time spent by caregivers, an outcome that is also associated with reduced indirect costs. A decision-analytic model that incorporated the progressive nature of AD demonstrated an average cost saving of $9250 for each patient started on tacrine at the time of diagnosis. This saving was attributed to the delay in nursing-home placement. Other studies have described a mathematical model that considers the relationship between cognitive performance and the cost of illness; it can be used to obtain an initial estimate of the economic benefit of new AD treatments. The available economic studies indicate that, when used appropriately, cholinesterase inhibitors improve outcomes and reduce costs for patients with mild to moderate AD.

Small GW, Donohue JA, Brooks RL. An economic evaluation of donepezil in the treatment of Alzheimer's disease. Clin Ther. 1998 Jul-Aug;20(4):838-50.

Using data from a longitudinal survey of caregivers of Alzheimer's disease patients, we calculated the average per-patient direct medical costs over a 6-month period for a matched sample of patients (N = 376). A group of patients receiving donepezil for 6 months was compared with a group not receiving this form of drug therapy. The groups were matched by disease severity, age, sex, and comorbidity. The average age in the two groups was 74 years, with 50% female and 90% white. Patients in both groups had a mean of 1.6 comorbid conditions. No patients in either group were institutionalized at the beginning of the 6-month period, and all patients were taking at least one prescription drug, including donepezil. Mean 6-month direct medical expenses for a patient receiving donepezil were $3443, including the cost of the drug, whereas the per-patient mean expenses for the comparison group were $3476. Although the patients receiving donepezil had greater expenditures for prescription drugs, these costs were offset by a slower rate of institutionalization. At the end of the 6-month period, 5% of donepezil patients were institutionalized, compared with 10% of the nondonepezil patients. The cost of receiving donepezil treatment for 6 months did not result in a significantly higher per-patient mean direct cost.

Ernst RL, Hay JW, Fenn C, Tinklenberg J, Yesavage JA. Cognitive function and the costs of Alzheimer disease. An exploratory study. Arch Neurol. 1997 Jun;54(6):687-93.

OBJECTIVE: To estimate the dollar savings in costs attainable from drug or other treatments for Alzheimer disease (AD) that stabilize or reverse patients' cognitive decline. METHODS: Medical and other disease-related utilization data were collected from the caregivers of 64 patients diagnosed as having probable AD. The quantities of utilization were priced at national levels to generate measures of illness costs. Costs per patient were then estimated as regression functions of scores on the Mini-Mental State Examination (MMSE), which was used as an index of patient cognitive function. Potential savings in illness costs were estimated by comparing predicted costs at various baseline and intervention-level values of the patient's MMSE score. RESULTS: The potential savings in illness costs attainable from treatment are small for mildly and very severely demented patients with AD. However, for moderately to severely demented home-dwelling patients having, say, an MMSE score of 7 at baseline, prevention of a 2-point decline in the score would save about $3700 annually, and a 2-point increase in an MMSE score rather than a 2-point decline would save about $7100. CONCLUSION: Large savings in the costs of caring for moderately to severely demented home-dwelling patients with AD may be achievable from disease interventions that have minor effects on patients' cognitive status.

Max W, Webber P, Fox P. Alzheimer's disease. The unpaid burden of caring. J Aging Health. 1995 May;7(2):179-99.

This study presents detailed estimates of the hours and cost of informal care provided to Alzheimer's disease patients in Northern California. Data were collected over 12 months from 93 community-residing patients and their caregivers and from 94 institutionalized patients and their caregivers. Patients residing in the community received an average of 286 hours per month of unpaid care, whereas institutionalized patients received 36 hours per month. Alternative methods of imputing informal costs are described. The annual value of informal care (in 1990 dollars) is $34,517 for the noninstitutionalized sample and $5,542 for the institutionalized sample. The determinants of informal caregiving were examined and compared in the two settings. The more cognitively impaired the individual, the higher the informal costs no matter what the residential setting. In an institutional setting, the younger the patient and caregiver, the higher the costs. If a caregiver is not a spouse, higher informal care costs were also found.

Ernst RL, Hay JW. The US economic and social costs of Alzheimer's disease revisited. Am J Public Health. 1994 Aug;84(8):1261-4.

OBJECTIVEs. An earlier paper estimated the per-case and national incidence costs of Alzheimer's disease for 1983. This paper updates the estimates of costs per case to 1991 and presents new national prevalence estimates of the economic and social costs of the disease. METHODS. All data for the cost estimates were taken from published sources or provided by other researchers. RESULTS. At midrange values of the estimated cost and epidemiological parameters, the discounted (at 4%) direct and total costs of Alzheimer's disease were $47,581 and $173,932 per case, respectively. The estimated 1991 national direct and total prevalence costs were $20.6 billion and $67.3 billion, respectively. Assuming conservatively that the prevalence of the disease remains constant, the estimated discounted present values of the direct and total costs of all current and future generations of Alzheimer's patients are $536 billion and $1.75 trillion, respectively. CONCLUSIONS. The $536 billion and $1.75 trillion figures are minimum estimates of the long-term dollar losses to the US economy in 1991 caused by Alzheimer's disease.

Volicer L, Collard A, Hurley A, Bishop C, Kern D, Karon S. Impact of special care unit for patients with advanced Alzheimer's disease on patients' discomfort and costs. J Am Geriatr Soc. 1994 Jun;42(6):597-603.

OBJECTIVE: To compare outcomes in patients with the clinical diagnosis of probable dementia of the Alzheimer type (DAT) cared for in a Dementia Special Care Unit (DSCU) with those in traditional long-term care (TLTC). DESIGN: Two-year prospective cohort study. SETTING: Two Veterans Administration Hospitals. The DSCU concentrated on assuring patients' comfort instead of promoting maximal survival; in some patients this excluded transfer to acute medical settings, the use of antibiotics, and tube feeding. MEASUREMENTS: Data were collected regarding disease severity, patient discomfort, use of medical resources, and mortality rate. RESULTS: Patients at both settings were similar on baseline measures, and most were severely demented. The monthly levels of observed discomfort were lower in DSCU than in TLTC patients. The costs of medications, radiology, and laboratory procedures were lower in DSCU than in TLTC patients. DSCU patients were also transferred less frequently to an acute medical setting. The average 3-month cost for a DSCU patient was $1477 less than the cost of care for a TLTC patient. However, DSCU patients with lower severity of DAT had a higher mortality rate then TLTC patients. CONCLUSIONS: These results suggest that management of patients with advanced DAT on a DSCU using a palliative care philosophy may result in less patient discomfort and lower costs than management on a TLTC.

Rice DP, Fox PJ, Max W, Webber PA, Lindeman DA, Hauck WW, Segura E. The economic burden of Alzheimer's disease care. Health Aff (Millwood). 1993 Summer;12(2):164-76.

This study examines total formal and informal care costs attributable to Alzheimer's disease for persons living in the community and in institutions. The total cost of caring for an Alzheimer's patient in northern California is approximately $47,000 per year whether the patient lives at home or in a nursing home, but the cost breakdown differs in the two settings. For community-resident patients, three-fourths of the total cost represents an imputed value for unpaid informal care compared with 12 percent for institutionalized patients. Formal services are financed primarily by individuals and their families. Over 60 percent of the services provided to patients in either care setting were paid out of pocket. With projected increases in the number of persons at risk of developing Alzheimer's disease, the economic impact of the disease on future long-term care costs will be significant.

Hay JW, Ernst RL. The economic costs of Alzheimer's disease. Am J Public Health. 1987 Sep;77(9):1169-75.

This paper estimates the economic costs of Alzheimer's Disease to individuals and to society, based on review of published Alzheimer's Disease-related research. The analysis is derived from epidemiological projections and cost information for the United States population in 1983. Estimated costs include both direct medical care and social support costs, as well as indirect costs, such as support services provided by family or volunteers, and the value of lost economic productivity in Alzheimer's Disease patients. Mid-range estimates of net annual expected costs for an Alzheimer's Disease patient, excluding the value of lost productivity, are $18,517 in the first year and $17,643 in subsequent years, with direct medical and social services comprising about half of these costs. Under base case assumptions, the total cost of disease per patient in 1983, was $48,544 to $493,277, depending upon patient's age at disease onset. The estimated present value of total net costs to society for all persons first diagnosed with Alzheimer's Disease in 1983 was $27.9-31.2 billion. Development of a public or private insurance market for the economic burdens of Alzheimer's Disease would fill some of the gaps in the current US system of financing long-term chronic disease care.

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