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J Alzheimers Dis. 2015;45(1):15-25. doi: 10.3233/JAD-142232.

A combination of supplements may reduce the risk of Alzheimer's disease in elderly Japanese with normal cognition.

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Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
Yashio Central General Hospital, Saitama, Japan.
Biostatistics Center, Kurume University, Fukuoka, Japan.
Department of Neuropsychiatry, University of Tsukuba, Ibaraki, Japan.


A number of studies have examined the effect of a single supplement against Alzheimer's disease (AD) with conflicting results. Taking into account the complex and multifactorial nature of AD pathogenesis, multiple supplements may be more effective. Physical activity is another prospect against AD. An open-label intervention study was conducted to explore a potential protective effect of multiple supplements and physical activity. Their interaction was also examined. Participants were community-dwelling volunteers aged 65 or older as of May 2001 in a rural area of Japan. Among 918 cognitively normal participants included in the analyses, 171 took capsules daily for three years that contained n-3 polyunsaturated fatty acid, Ginkgo biloba leaf dry extracts, and lycopene. Two hundred and forty one participants joined the two-year exercise intervention that included a community center-based and a home-based exercise program. One-hundred and forty eight participated in both interventions. A standardized neuropsychological battery was administered at baseline in 2001, the first follow-up in 2004-2005, and the second in 2008-2009. The primary outcome was AD diagnosis at follow-ups. A complementary log-log model was used for survival analysis. A total of 76 participants were diagnosed with AD during follow-up periods. Higher adherence to supplementation intervention was associated with lower AD incidence in both unadjusted and adjusted models. Exercise intervention was also associated with lower AD incidence in the unadjusted model, but not in the adjusted model. We hypothesized that the combination of supplements acted in a complementary and synergistic fashion to bring significant effects against AD occurrence.


Alzheimer's disease; Gingko biloba; dietary supplements; exercise; intervention study; lycopene; n-3 PUFA

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