Omega-3, isoflavones & amyloid deposition in cognitively normal elderly Japanese

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 DESCRIPTION (provided by applicant): Recent progress in neuroimaging has made it possible to evaluate amyloid deposition in the brain with Pittsburgh compound B (PiB). Amyloid deposition is an independent risk factor for Alzheimer's disease (AD). The majority of elderly aged 80-89 with normal cognition (NC) have amyloid deposition. No studies have found a population where prevalence of amyloid deposition is low among elderly with NC. Finding such a population is a first step to identifying risk factors for AD. Japanese have the greatest longevity; while their prevalence of apolipoprotein E4, the major genetic risk factor for AD, is similar to the US, Japanese have a considerably different diet characterized by markedly high dietary intake of marine omega-3 fatty acids (omega-3 FAs) and soy isoflavones (ISF) (both are >10x higher than in the US) for the past 50 years. Many observational studies reported that dietary intake of omega-3 FAs is inversely associated with incident dementia and AD. A recent study in Japan reported that high dietary intake of soy, which is the source of ISF, is inversely associated with incident dementia and AD. Suggested evidence from a small number of elderly volunteers with NC shows that Japanese have very low prevalence of amyloid deposition. We hypothesize that 1) Japanese elderly aged 80- 89 with NC have significantly lower prevalence of amyloid deposition in the brain than in the US and 2) in Japanese elderly aged 80-89 with NC, midlife serum levels of each of omega-3 FAs and ISF have significant inverse associations with late-life amyloid deposition. To test our hypotheses, we will enroll 200 Japanese men and women (100 each) aged 80-89 with NC randomly selected from the Suita Study in Japan: a population- based prospective cohort study of 6,406 subjects aged 30-79 at baseline in 1994. We will examine these 200 subjects for PiB standardized to US studies. We will also examine the association of midlife levels of each of omega-3 FAs and ISF with late-life amyloid deposition using stored serum samples. The findings of low prevalence of amyloid deposition in the brain and significant inverse associations of omega-3 FAs and/or ISF with amyloid deposition will have major impact on research into the etiology and potentially the prevention of AD.