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Article type: Research Article
Authors: Li, Lily | Cavuoto, Marina ; 1 | Biddiscombe, Karen; 2 | Pike, Kerryn E.; *
Affiliations: School of Psychology & Public Health, La Trobe University, Melbourne, Victoria, Australia
Correspondence: [*] Correspondence to: Kerryn E. Pike, Department of Psychology & Counselling, School of Psychology & Public Health, La Trobe University, Melbourne, 3086 Australia. Tel.: +61 3 9479 1381; E-mail: [email protected].
Note: [1] Present address: Institute for Breathing & Sleep, Austin Health, Heidelberg, Victoria, Australia.
Note: [2] Present address: Mary Mackillop Institute of Health Research, Australian Catholic University, Melbourne, Australia.
Abstract: Background:Dementia is a devastating condition for older adults, with both modifiable (e.g., diabetes mellitus) and unmodifiable risk factors (e.g., APOE ɛ4 allele). It remains unclear how, and to what extent, diabetes impacts dementia risk via both cerebrovascular and amyloid-β pathways. Objective:We conducted a quantitative meta-analysis to investigate the contribution of diabetes to incident dementia risk in people with ɛ4 and, based on the vascular-related neuropathology of diabetes, whether the combination of these factors increases risk for vascular dementia versus Alzheimer’s disease (AD). Methods:Systematic literature searches were conducted using EMBASE, MEDLINE, PsycINFO, and CINAHL databases. Pooled relative risk (RR) estimates were calculated using a random effects model, and subgroup analyses conducted across dementia subtypes. Results:Twelve studies were included, with a total of 16,200 participants. Considered concurrently, diabetes increased incident dementia risk an additional 35% for those with ɛ4 (RR = 1.35, 95% CI = 1.13–1.63). Similar patterns were observed for AD and vascular dementia. Conclusion:Interventions to prevent co-morbid diabetes, and diabetes-related complications and neuropathological changes, may be one way of modifying dementia risk in the vulnerable ɛ4 population.
Keywords: Alzheimer’s disease, Apolipoproteins E, dementia, diabetes mellitus, risk factors, vascular dementia
DOI: 10.3233/JAD-191068
Journal: Journal of Alzheimer's Disease, vol. 74, no. 4, pp. 1295-1308, 2020
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