Figueroa R, Steenland K, MacNeil JR, Levey AI, Vega IE. Geographical differences in the occurrence of Alzheimer's disease mortality: United States versus Puerto Rico. Am J Alzheimers Dis Other Demen. 2008 Oct-Nov;23(5):462-9.

Since the implementation of the 10th International Classification of Disease in 1999, the trend in Alzheimer's disease mortality rate has not been reported. Here, the age-adjusted Alzheimer's disease mortality rate in Puerto Rico and United States from 1999 to 2004 was analyzed. The results showed an increasing trend in Alzheimer's disease mortality rate in both the United States and Puerto Rico. However in Puerto Rico, the Alzheimer's disease mortality rate (32.4/100,000) was higher than that observed in United States (20.9/100,000). Interestingly, the Alzheimer's disease mortality rate of Puerto Ricans living in Puerto Rico is much higher than Puerto Ricans living in the United States. The higher occurrence of Alzheimer's disease mortality in Puerto Rico versus the United States could be explained by factors such as coding practices, genetics, socioeconomics, and health care. These results highlight the need for comprehensive studies on factors that may influence diagnosis, death certificate coding practices, and development of Alzheimer's disease pathology in different geographical regions.

Olarte L, Schupf N, Lee JH, Tang MX, Santana V, Williamson J, Maramreddy P, Tycko B, Mayeux R. Apolipoprotein E epsilon4 and age at onset of sporadic and familial Alzheimer disease in Caribbean Hispanics. Arch Neurol. 2006 Nov;63(11):1586-90.

BACKGROUND: The primary effect of the apolipoprotein E epsilon4 (APOE epsilon4) allele is on the age at onset of Alzheimer disease (AD). OBJECTIVE: To investigate whether the presence of the APOE epsilon4 allele can account for the earlier age at onset of familial AD (FAD) compared with sporadic AD (SAD). DESIGN: Population-based, case series ascertained in a prospective study of aging and dementia in Medicare recipients aged 65 years or older. SETTING: Clinics in northern Manhattan and in the Dominican Republic and Puerto Rico. PARTICIPANTS: There were 680 Caribbean Hispanic subjects: 111 patients with FAD, with at least 1 family member with dementia; 163 patients with SAD; and 406 elderly persons without dementia or other illnesses. Main Outcome Measure Age at onset of dementia was examined in relation to frequency of APOE epsilon4. Sex, education, and medical risk factors for stroke, hypertension, diabetes, and heart disease were examined as effect modifiers. RESULTS: The mean age at onset of AD was significantly lower in FAD than in SAD, and a statistically significant dose effect of the APOE epsilon4 allele was present for age at onset in FAD (P = .001) but not in SAD. The age at onset in patients homozygous for the APOE epsilon4 allele with FAD and SAD was similar. Compared with SAD, the major difference was younger age at onset in patients with FAD who were heterozygous for the APOE epsilon4 allele and those without an APOE epsilon4 allele. CONCLUSIONS: Apolipoprotein E epsilon4 had a consistent lowering effect on age at onset of FAD, but this was attenuated in SAD. This suggests that among individuals with a family history of AD and the APOE epsilon4 allele, additional genetic or environmental factors may accelerate the onset of dementia.

Rippon GA, Tang MX, Lee JH, Lantigua R, Medrano M, Mayeux R. Familial Alzheimer disease in Latinos: interaction between APOE, stroke, and estrogen replacement. Neurology. 2006 Jan 10;66(1):35-40.

BACKGROUND: Factors that modify risk related to APOE variants have been examined primarily in unrelated patients and controls, but seldom in family-based studies. Stroke, vascular risk factors, estrogen replacement therapy (ERT), head injury (HI), and smoking have been reported to influence risk of sporadic but not familial Alzheimer disease (AD). OBJECTIVES: To examine the potential relationship between these risk factors and APOE, the authors used a family study design in a population in which the APOE-epsilon4 variant is strongly associated with risk of AD. METHODS: Latino families primarily from the Caribbean Islands in which two or more living relatives had dementia were identified in the New York City metropolitan area, the Dominican Republic, and Puerto Rico. A total of 1,498 participants from 350 families underwent a clinical interview, medical and neurologic examinations, neuropsychological testing, and APOE genotyping. Diagnosis was made by consensus using research criteria for AD. RESULTS: APOE-epsilon4 was associated with a nearly twofold increased risk of AD. A history of stroke was also associated with a fourfold increased risk. A statistical interaction between APOE-epsilon4 and stroke was observed. Women with an APOE-epsilon4 who took ERT did not have an increased risk of AD, but in women with a history of stroke ERT was a deleterious effect modifier. CONCLUSIONS: APOE-epsilon4 and stroke independently increase risk of familial Alzheimer disease (AD) among Latinos, and may interact to further increase AD risk. Among women, the risk of AD associated with APOE-epsilon4 may be attenuated by a history of ERT.