Interaction between APOE Genotype and Diabetes in Longevity

Mitsuru Shinohara, Kaoru Suzuki, Guojun Bu, Naoyuki Sato

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)719-726
Number of pages8
JournalJournal of Alzheimer's Disease
Issue number2
StatePublished - 2021


  • Apolipoprotein E
  • Dementia
  • Diabetes
  • Longevity

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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