@article{c649de16356540ac899ff0c09921e6d9,
title = "Interaction between APOE genotype and diabetes in cognitive decline",
abstract = "Introduction: Although diabetes and apolipoprotein E (apoE) are both significant risk factors for dementia, including Alzheimer's disease, it remains to be clarified how they are related to each other in contributing to the risk of dementia. Methods: By reviewing the National Alzheimer's Coordinating Center (NACC) clinical records, we investigated whether diabetes affects cognitive decline depending on APOE genotype and their potential relationships with neuropathology. Results: A significant interaction between diabetes and APOE genotype exists, where diabetes affected cognitive decline in APOE3 carriers and APOE2 carriers, but not APOE4 carriers. Moreover, the presence of vascular pathology was increased by diabetes in APOE3 carriers, while APOE4 carriers nearly reached plateau levels irrespective of diabetes. Discussion: Diabetes accelerates cognitive decline, in part, through accelerating vascular impairment in non-APOE ε4 carriers, but such effects are negligible in APOE4 carriers, who themselves are already vulnerable to vascular impairment.",
keywords = "APOE, Alzheimer's disease, cognitive decline, dementia, diabetes",
author = "Mitsuru Shinohara and Yoshitaka Tashiro and Kaoru Suzuki and Akio Fukumori and Guojun Bu and Naoyuki Sato",
note = "Funding Information: We would like to thank the contributors to the NACC database for collecting the data. We would like to thank Dr. Wataru Ohashi for helping statistical analyses, and 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 (28-45 to Naoyuki Sato); Grants-in-Aid from Japan Promotion of Science (MEXT26293167, MEXT15K15272, and MEXT17H04154 to Naoyuki Sato and 17H07419 and 18H02725 to Mitsuru Shinohara); a Takeda Science Foundation Research Encouragement Grant (to Naoyuki Sato and Mitsuru Shinohara); a SENSHIN Medical Research Foundation Research Grant (to Naoyuki Sato); a Novartis Foundation for Gerontological Research Award (to Naoyuki Sato); an Annual Research Award Grant from the Japanese Society of Anti-aging Medicine (to Naoyuki Sato); a NACC Junior Investigator Award (to Mitsuru Shinohara); a Takeda Medical Research Foundation Research Grant (to Naoyuki Sato); a research grant from the Japan Foundation for Aging and Health (to Mitsuru Shinohara); a research grant from the Uehara Memorial Foundation (to Mitsuru Shinohara); a research grant from the Hori Sciences and Arts Foundation (to Mitsuru Shinohara); and National Institutes of Health (NIH) grants R37AG027924, RF1AG057181, and R01AG035355 (to Guojun Bu). The NACC database is funded by NIH grant U01AG016976. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, 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), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI M. Marsel Mesulam, MD), 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), P50 AG005131 (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 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD). Publisher Copyright: {\textcopyright} 2020 the Alzheimer's Association",
year = "2020",
month = jan,
doi = "10.1002/dad2.12006",
language = "English (US)",
volume = "12",
journal = "Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring",
issn = "2352-8729",
publisher = "Elsevier BV",
number = "1",
}