Journal
ALZHEIMER DISEASE & ASSOCIATED DISORDERS
Volume 34, Issue 1, Pages 10-17Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/WAD.0000000000000332
Keywords
diabetes; Alzheimer disease; everyday functioning; subtle cognitive decline
Categories
Funding
- NIH [R01 AG049810, K24 AG026431]
- Alzheimer's Association [AARF-17-528918, AARG-17-500358, AARG-18-566254]
- U.S. Department of Veterans Affairs Clinical Sciences Research and Development Service [1IK2CX001415, 1IK2CX000938]
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Araclon Biotech
- BioClinica Inc.
- Biogen
- Bristol-Myers Squibb Company
- CereSpir Inc.
- Cogstate
- Eisai Inc.
- Elan Pharmaceuticals Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Genentech Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd
- Janssen Alzheimer Immunotherapy Research & Development, LLC
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Lumosity
- Lundbeck
- Merck Co. Inc.
- Meso Scale Diagnostics LLC
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
- Alzheimer's Drug Discovery Foundation
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Objective: The current study examined the interactive effect of type 2 diabetes and Alzheimer disease (AD) risk factors on the rate of functional decline in cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative. Methods: Participants underwent annual assessments that included the Functional Activities Questionnaire, an informant-rated measure of everyday functioning. Multilevel modeling, controlling for demographic variables and ischemic risk, examined the interactive effects of diabetes status (diabetes, n=69; no diabetes, n=744) and AD risk factors in the prediction of 5-year longitudinal change in everyday functioning. One model was run for each AD risk factor, including: objectively-defined subtle cognitive decline (Obj-SCD), and genetic susceptibility [apolipoprotein E epsilon 4 (APOE epsilon 4) as well as cerebrospinal fluid beta-amyloid (A beta), total tau (tau), and hyperphosphorylated tau (p-tau). Results: The 3-way diabetesxAD risk factorxtime interaction predicted increased rates of functional decline in models that examined Obj-SCD, APOE epsilon 4, tau, and p-tau positivity, but not A beta positivity. Conclusions: Participants with both diabetes and at least 1 AD risk factor (ie, Obj-SCD, APOE epsilon 4, tau, and p-tau positivity) demonstrated faster functional decline compared with those without both risk factors (diabetes or AD). These findings have implications for early identification of, and perhaps earlier intervention for, diabetic individuals at risk for future functional difficulty.
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