Insulin and Sex Interactions in Older Adults with Mild Cognitive Impairment

Article type: Research Article

Authors: Cholerton, Brenna^{a; *} | Baker, Laura D.^{a; b} | Trittschuh, Emily H.^{a; b} | Crane, Paul K.^c | Larson, Eric B.^{c; f} | Arbuckle, Matthew^a | Saucedo, Hector Hernandez^a | McCurry, Susan M.^e | Bowen, James D.^{d; g} | McCormick, Wayne C.^c | Craft, Suzanne^{a; b}

Affiliations: [a] Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA | [b] Department of Psychiatry and Behavioral Science, University of Washington School of Medicine, Seattle, WA, USA | [c] Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA | [d] Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA | [e] Department of Psychosocial and Community Health, University of Washington School of Medicine, Seattle, WA, USA | [f] Group Health Research Institute, Seattle, WA, USA | [g] Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA, USA

Correspondence: [*] Correspondence to: Brenna Cholerton, PhD, VA Puget Sound Health Care System, GRECC-A-182, 9600 Veterans Dr SW, Tacoma, WA 98493, USA. Tel.: +1 253 583 2032; Fax: +1 253 589 4073; E-mail: bchol@u.washington.edu.

Abstract: Alzheimer's disease (AD) and other dementias are likely preceded by a protracted preclinical state. Thus, identification of biomarkers that signal potential points of intervention during this prodromal phase (during which patients are largely able to compensate for their cognitive deficits) is of paramount importance. Insulin is a pancreatic hormone with potent central nervous system effects, and insulin dysregulation has been implicated in the pathogenesis of both AD and vascular dementia. The aim of the current study was to determine whether circulating insulin differs as a function of mild cognitive impairment (MCI) diagnosis, and whether this relationship is mediated by sex and apolipoprotein E (APOE) genotype. A sample of 549 nondemented participants aged 65 and over from the Adult Changes in Thought community-based cohort underwent cognitive testing and blood draw to determine fasting levels of plasma insulin. Subjects were categorized as having normal cognitive functioning, amnestic MCI, or nonamnestic MCI. Results showed that the relationship between insulin and diagnostic category is moderated by sex, such that men with nonamnestic or amnestic MCI have higher fasting plasma insulin than cognitively normal men, while women with amnestic MCI have lower fasting plasma insulin than cognitively normal women. Exploratory analyses suggest that APOE ε4 genotype may further influence the relationship between sex and insulin. Future research will help determine whether insulin dysregulation results in differential effects on vascular function and AD pathology as a function of sex and/or APOE genotype.

Keywords: Age-related memory disorders, aging, Alzheimer's disease, cognition, dementia, hyperinsulinemia, insulin, vascular

DOI: 10.3233/JAD-2012-120202

Journal: Journal of Alzheimer's Disease, vol. 31, no. 2, pp. 401-410, 2012