Kessing LV, Søndergård L, Forman JL, Andersen PK. Lithium treatment and risk of dementia. Arch Gen Psychiatry. 2008 Nov;65(11):1331-5.

CONTEXT: It has been suggested that lithium may have neuroprotective abilities, but it is not clear whether lithium reduces the risk of dementia. OBJECTIVE: To investigate whether continued treatment with lithium reduces the risk of dementia in a nationwide study. DESIGN: An observational cohort study with linkage of registers of all patients prescribed lithium and diagnosed as having dementia in Denmark from January 1, 1995, through December 31, 2005. SETTING: We identified all patients treated with lithium in Denmark within community psychiatry, private specialist, and general practices and a random sample of 30% of the general population. Subjects A total of 16,238 persons who purchased lithium at least once and 1,487,177 persons from the general population who did not purchase lithium. Main Outcome Measure Diagnosis of dementia or Alzheimer disease during inpatient or outpatient hospital care. RESULTS: Persons who purchased lithium at least once had an increased rate of dementia compared with persons not exposed to lithium (relative risk, 1.47; 95% confidence interval, 1.22-1.76). For persons who continued to take lithium, the rate of dementia decreased to the same level as the rate for the general population. The rate of dementia decreased early after the consumption of lithium tablets corresponding to 1 prescription (typically 100 tablets) and stayed at a low level, although with a slight increase according to the number of subsequent prescriptions. The association between the number of prescriptions for lithium and dementia was unique and different from the association between the number of prescriptions for anticonvulsants and dementia. All findings were replicated in subanalyses with Alzheimer disease as the outcome. CONCLUSIONS: Continued lithium treatment was associated with reduction of the rate of dementia to the same level as that for the general population. Methodological reasons for this finding cannot be excluded, owing to the nonrandomized nature of data.

Erlangsen A, Zarit SH, Conwell Y. Hospital-diagnosed dementia and suicide: a longitudinal study using prospective, nationwide register data. Am J Geriatr Psychiatry. 2008 Mar;16(3):220-8.

OBJECTIVE: The current study aims to examine the risk of suicide in persons diagnosed with dementia during a hospitalization and its relationship to mood disorders. DESIGN: Event-history analysis using time-varying covariates. SETTING: Population-based record linkage. PARTICIPANTS: All individuals aged 50+ living in Denmark (N=2,474,767) during January 1, 1990 through December 31, 2000. MEASUREMENTS: Outcome of interest is suicide. Relative risks are calculated based on person-days spent in each stratum. RESULTS: A total of 18,648,875 person-years were observed during the 11-year study period. During this period, 136 persons who previously had been diagnosed with dementia died by suicide. Men and women aged 50-69 years with hospital presentations of dementia have a relative suicide risk of 8.5 (95% confidence interval: 6.3-11.3) and 10.8 (95% confidence interval: 7.4-15.7), respectively. Those who are aged 70 or older with dementia have a threefold higher risk than persons with no dementia. The time shortly after diagnosis is associated with an elevated suicide risk. The risk among persons with dementia remains significant when controlling for mood disorders. As many as 26% of the men and 14% of the women who died by suicide died within the first 3 months after being diagnosed whereas 38% of the men and 41% of the women died more than 3 years after initial dementia diagnosis. CONCLUSIONS: Dementia, determined during hospitalization, was associated with an elevated risk of suicide for older adults. Preventive measures should focus on suicidal ideation after initial diagnosis but also acknowledge that suicides can occur well after a dementia diagnosis has been established.

Kessing LV, Harhoff M, Andersen PK. Treatment with antidepressants in patients with dementia--a nationwide register-based study. Int Psychogeriatr. 2007 Oct;19(5):902-13. Epub 2006 Oct 23.

BACKGROUND: Depression and anxiety is prevalent among patients with dementia but the extent to which these conditions are treated with antidepressants has not previously been investigated. METHODS: Nationwide register-based data in Denmark were used to identify all patients diagnosed with dementia or osteoarthritis at hospital admission or at first outpatient contact during the period 1995-2000. Rates of subsequent purchase of antidepressants from pharmacies were then calculated. Further, the rate of antidepressant use for patients with dementia was compared with the rate in a gender-, age-, and calendar-matched sample of the general population. RESULTS: In total, 24,137 patients with a main diagnosis of dementia and 100,378 patients with a main first diagnosis of osteoarthritis were incorporated in the study. A total of 43.2% of patients with dementia received antidepressants during follow-up compared to 16.0% of patients with osteoarthritis. Among patients with a diagnosis of dementia, the rate of subsequently purchasing antidepressants was 4.17 times higher (95% CI = 4.05-4.29) than that of patients with a first diagnosis of osteoarthritis, and 8.85 times higher (95% CI = 8.68-9.03) than that of a gender-, age- and calendar-matched sample of the general population. The rate was increased in all subgroups of patients regardless of gender, age, socio-economic group and time since diagnosis. CONCLUSIONS: The findings challenge the widely held contention that depression and anxiety in patients with dementia is underdiagnosed and undertreated in clinical practice.

Andersen K, Lolk A, Kragh-Sørensen P, Petersen NE, Green A. Depression and the risk of Alzheimer disease. Epidemiology. 2005 Mar;16(2):233-8.

BACKGROUND: Several epidemiologic studies have examined depression as a risk factor for Alzheimer disease with conflicting results. Most studies relied on self-reported depression, but the agreement between self-reported depression and clinical diagnosis has been reported to be weak, thereby diluting the association. METHODS: A population-based cohort in Odense, Denmark, of 3346 persons age 65-84 years was examined at baseline (1992-1994) and after 2 years (1994-1996) and 5 years (1997-1999). History of depression was collected at baseline as self-report. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Persons with a history of depression had an increased risk of Alzheimer disease both at baseline (OR = 1.7; CI = 1.0-2.7) and at follow up (at 2 years, 1.9 [1.0-3.3] and at 5 years, 1.6 [0.9-2.7]). CONCLUSIONS: Depression was associated with an increased risk of Alzheimer disease. The odds ratios were lower than generally reported from follow-up studies and are similar to cross-sectional studies.

Andersen K, Lolk A, Nielsen H, Kragh-Sørensen P. [Prevalence and incidence of dementia in Denmark. The Odense study] Ugeskr Laeger. 2000 Aug 14;162(33):4386-90.

Prevalence and incidence of dementia were determined for 65-84 year-old persons living in the municipality of Odense and randomly drawn from the Danish Civil Registration System (DCRS). All participants were examined with CAMCOG, the cognitive section of CAMDEX (The Cambridge Examination for Mental Disorders of the Elderly) and the follow-up period was two years. Individualized CAMCOG cut-off scores were determined by multiple linear regression. Possibly demented persons were further examined with the remaining part of CAMDEX and neuropsychological tests. Alzheimer's disease (AD) was diagnosed according to the NINCDS-ADRDA criteria for probable AD, and vascular dementia (VD) and dementias of other types according to the DSM-III-R criteria for dementia. The severity of dementia was determined according to the Clinical Dementia Rating scale. Of the 5,237 persons drawn from the DCRS, 3,346 participated in the prevalence study and 2,452 in the incidence study. The prevalence was 7.1% (66.7% AD, 18.3% VD, and 15.0% dementias of other types). Ninety-six (2.8%) were diagnosed as very mildly demented. The incidence rate was 29.5 new cases per 1,000 person-years and 20.9 for AD. Inclusion of cases with very mild dementia resulted in higher prevalence and incidence rates than generally reported.

Andersen K, Nielsen H, Lolk A, Andersen J, Becker I, Kragh-Sørensen P. Incidence of very mild to severe dementia and Alzheimer's disease in Denmark: the Odense Study. Neurology. 1999 Jan 1;52(1):85-90.

OBJECTIVE: Calculation of incidence of dementia and AD, including cases in the earliest phases of the diseases. BACKGROUND: Establishment of incidence estimates is important for the future planning of the health care system, and incidence studies can offer insights into risk factors. METHODS: A total of 5,237 persons age 65 to 84 years were randomly drawn among people living in the municipality of Odense, Denmark. Of this sample 3,086 persons were eligible for the incidence study. All participants were examined with CAMCOG, the cognitive section of The Cambridge Examination for Mental Disorders of the Elderly (CAMDEX), and the follow-up period was 2 years. Using multiple linear regression, the CAMCOG cutoff score was individualized to detect even minor cognitive decline with optimal precision. Possibly demented persons were further examined with the remaining part of the CAMDEX and neuropsychological tests. AD was diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable AD, and vascular dementia and dementia of other types were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised) criteria for dementia. Finally, the severity of dementia was determined according to the Clinical Dementia Rating scale. RESULTS: The incidence rate for very mild to severe dementia was 29.5 per 1,000 person-years and 20.9 for AD, and the rates were similar for men and women. CONCLUSION: Application of an individualized cutoff for the screening instrument resulted in detection of a substantial number of cases with very mild dementia, which subsequently resulted in higher incidence rates than those reported in most other studies.

Andersen K, Lolk A, Nielsen H, Andersen J, Olsen C, Kragh-Sørensen P. Prevalence of very mild to severe dementia in Denmark. Acta Neurol Scand. 1997 Aug;96(2):82-7.

OBJECTIVES: The prevalence of dementia has been estimated in several countries and a meta-analysis has shown moderate and severe dementia in people aged 65 years and older to be between 4% and 6%. The Odense study is aiming to estimate the prevalence and incidence of dementia and to identify risk factors. MATERIAL AND METHODS: A total of 3346 persons, equivalent to 64.5% of a random sample of 5237 persons aged 65-84 years living in the municipality of Odense, Denmark, underwent a two phase diagnostic procedure including a screening with CAMCOG, the cognitive section of The Cambridge Examination for Mental Disorders of the Elderly, seven neuropsychological tests, medical examination, and CT scan. The severity of dementia was assessed by the CDR (Clinical Dementia Rating). RESULTS: The prevalence rate was 7.1%, including the very mildly demented, defined as persons rated questionably demented according to the CDR scale. The prevalence rate of very mild dementia was 2.8%. The proportion of cases with very mild dementia decreased with increasing age while the prevalence rate increased. CONCLUSION: Inclusion of very mild cases of dementia resulted in a higher prevalence rate than generally reported, and the prevalence rate increased exponentially with age which was mainly due to Alzheimer's disease.