Affiliations: [a] Department of Aging Neurobiology, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan
| [b] Department of Aging Neurobiology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| [c] Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
Correspondence:
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Correspondence to: Mitsuru Shinohara, PhD, Associate Professor and Naoyuki Sato, MD, PhD, Professor, Department of Aging Neurobiology, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, 7-430, Morioka, Obu, Aichi 474-8511, Japan. Tel.: +81 562 46 2311 (ex. 6305, 6331); Fax: +81 562 44 6597; E-mail: shinohara@ncgg.go.jp; E-mail: nsato@ncgg.go.jp.
Abstract: Background:While both apolipoprotein E (APOE) genotype and diabetes affect longevity as well as Alzheimer’s disease, their relationship remains to be elucidated. Objective:The current study investigated the potential interaction between diabetes and APOE for lifespan and their relationship with cognitive status. Methods:We reviewed the National Alzheimer’s Coordinating Center (NACC) dataset, which documents longitudinally clinical records of 24,967 individuals with APOE genotype and diabetic status. Results:Diabetes was associated with shorter lifespan in APOE3 carriers (n = 12,415, HR = 1.29, 95%CI = 1.17–1.42, p < 0.001) and APOE2 carriers (n = 2,390, HR = 1.37, 95%CI = 1.10–1.69, p = 0.016), while such associations were weaker and not significant in APOE4 carriers (n = 9,490, HR = 1.11, 95%CI = 0.99–1.24, p = 0.162). As there is a significant interactive effect of cognitive status and diabetes on lifespan (p < 0.001), we stratified subjects by cognitive status and observed persistent APOE-dependent harmful effects of diabetes in nondemented individuals but not demented individuals. Notably, questionnaire-based activity status, with which we previously observed an association between APOE genotype and longevity, was also significantly affected by diabetes only in non-APOE4 carriers. Conclusion:The effects of diabetes on longevity vary among APOE genotype. These effects are observed in nondemented individuals and are potentially associated with activity status during their lifespan.
Keywords: Apolipoprotein E, dementia, diabetes, longevity
