title: Insulin and sex interactions in older adults with mild cognitive impairment.
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.
authors.affiliation: Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98493, USA. bchol@u.washington.edu
authors.forename: Brenna
authors.initials: B
authors.lastname: Cholerton
authors.forename: Laura D
authors.initials: LD
authors.lastname: Baker
authors.forename: Emily H
authors.initials: EH
authors.lastname: Trittschuh
authors.forename: Paul K
authors.initials: PK
authors.lastname: Crane
authors.forename: Eric B
authors.initials: EB
authors.lastname: Larson
authors.forename: Matthew
authors.initials: M
authors.lastname: Arbuckle
authors.forename: Hector Hernandez
authors.initials: HH
authors.lastname: Saucedo
authors.forename: Susan M
authors.initials: SM
authors.lastname: McCurry
authors.forename: James D
authors.initials: JD
authors.lastname: Bowen
authors.forename: Wayne C
authors.initials: WC
authors.lastname: McCormick
authors.forename: Suzanne
authors.initials: S
authors.lastname: Craft
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood* / Q000523:psychology*; D015415:Biomarkers / Q000097:blood; D060825:Cognitive Dysfunction / Q000097:blood* / Q000175:diagnosis / Q000523:psychology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D012307:Risk Factors; D012727:Sex Characteristics
chemical_list: D015415:Biomarkers; D007328:Insulin