TY - JOUR
T1 - Interaction between APOE Genotype and Diabetes in Longevity
AU - Shinohara, Mitsuru
AU - Suzuki, Kaoru
AU - Bu, Guojun
AU - Sato, Naoyuki
N1 - Funding Information:
This work was supported in part by the Research Funding for Longevity Sciences from National Center for Geriatrics and Gerontology (19-3 and 19-9 to NS; 19-18 to MS); Grants-in-Aid from Japan Promotion of Science (MEXT17H04154 to NS; 17H07419 and 18H02725 to MS); a NACC Junior Investigator Award (to MS); research grants from the Hori Sciences and Arts Foundation (to MS), Yokoyama Foundation for Clinical Pharmacology (to MS), the Ichiro Kanehara Foundation (to MS), ONO Medical Research Foundation (to MS); and National Institutes of Health (NIH) grants R37AG027924, RF1AG057181, RF1AG046205 (to GB). The NACC database is funded by NIH grant U01AG016976. The NACC data are contributed by the NIA-funded ADRCs: P30 AG019610 (PI Eric Reiman, MD), P30AG013846 (PI NeilKowall, MD), P30 AG062428-01 (PI James Leverenz, MD) P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P30 AG062421-01 (PI Bradley Hyman, MD, PhD), P30 AG062422-01 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P30 AG062429-01(PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P30 AG062715-01 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), and P50 AG047270 (PI Stephen Strittmatter, MD, PhD)
Funding Information:
The NACC database is funded by NIH grant U01AG016976. The NACC data are contributed by the NIA-funded ADRCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG062428-01 (PI James Leverenz, MD) P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P30 AG062421-01 (PI Bradley Hyman, MD, PhD), P30 AG062422-01 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Hender-son, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P30 AG062429-01(PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Tro-janowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P30 AG062715-01 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), and P50 AG047270 (PI Stephen Strittmatter, MD, PhD).
Funding Information:
We would like to thank the contributors to the NACC database for collecting the data. We would like to thank the lab members in the department of Aging Neurobiology and Dr. Takashi Sakurai for discussions. This work was supported in part by the Research Funding for Longevity Sciences from National Center for Geriatrics and Gerontology (19-3 & 19-9 to NS; 19-18 to MS); Grants-in-Aid from Japan Promotion of Science (MEXT17H04154 to NS; 17H07419 & 18H02725 to MS); a NACC Junior Investigator Award (to MS); research grants from the Hori Sciences and Arts Foundation (to MS), Yokoyama Foundation for Clinical Pharmacology (to MS), the Ichiro Kanehara Foundation (to MS), ONO Medical Research Foundation (to MS); and National Institutes of Health (NIH) grants R37AG027924, RF1AG057181, RF1AG046205 (to GB).
Publisher Copyright:
© 2021 - IOS Press. All rights reserved.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Apolipoprotein E
KW - Dementia
KW - Diabetes
KW - Longevity
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U2 - 10.3233/JAD-210125
DO - 10.3233/JAD-210125
M3 - Article
C2 - 34092638
AN - SCOPUS:85111386844
SN - 1387-2877
VL - 82
SP - 719
EP - 726
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 2
ER -