Development of a New Method for Assessing Global Risk of Alzheimer’s Disease for Use in Population Health Approaches to Prevention

Alzheimer’s disease (AD) affects approximately 35 million people worldwide. Increasing evidence suggests that many risk factors for AD are modifiable. AD pathology develops over decades. Hence risk reduction interventions require very long follow-ups to show effects on AD incidence. Focussing on AD risk, instead of diagnosis, provides a more realistic target for prevention strategies. We developed a novel methodology that yields a global approach to risk assessment for AD for use in population-based settings and interventions. The methodology was used to develop a risk assessment tool that can be updated as more evidence becomes available. First, a systematic search strategy identified risk and protective factors for AD. Eleven risk factors and four protective factors for AD were identified for which odds ratios were published or could be calculated (age, sex, education, body mass index, diabetes, depression, serum cholesterol, traumatic brain injury, smoking, alcohol intake, social engagement, physical activity, cognitive activity, fish intake, and pesticide exposure). An algorithm was developed to combine the odds ratios into an AD risk score. The approach allows for interactions among risk factors which provides for their varying impact over the life-course as current evidence suggests midlife is a critical period for some risk factors. Finally, a questionnaire was developed to assess the risk and protective factors by self-report. Compared with developing risk indices on single cohort studies, this approach allows for more risk factors to be included, greater generalizeability of results, and incorporation of interactions based on findings from different stages of the lifecourse. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11121-012-0313-2) contains supplementary material, which is available to authorized users

Alzheimer's disease and type 2 diabetes: the association study of polymorphisms in tumor necrosis factor-alpha and apolipoprotein E genes

Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two progressive disorders with high prevalence worldwide. Polymorphisms in tumor necrosis factor-alpha (TNF-?) and apolipoprotein E (ApoE) genes might be associated with both T2D and AD, representing possible genetic markers for the development of the AD in subjects with T2D. The aim was to determine ApoE and G-308A TNF-? gene polymorphisms in unrelated Croatian Caucasians: 207 patients with sporadic AD, 196 T2D patients and 456 healthy controls. Patients with AD had higher frequency of ApoE4 allele compared to T2D patients and controls. The significant association, observed between ApoE2 allele and T2D, disappeared after the data were adjusted for age and sex. The genotype or allele frequencies of G-308A TNF-? gene polymorphism were similar among the patients with AD, T2D and healthy controls. In conclusion, these results do not support the hypothesis that the A allele of G-308A TNF-? gene polymorphism is associated either with AD or T2D. Our data confirm the association between the ApoE4 allele and AD, and point out the E2 allele of ApoE gene as the possible risk factor for T2D