Association Between Insulin Resistance, Plasma Leptin, and Neurocognition in Vascular Cognitive Impairment

BACKGROUND Greater body weight has been associated impairments in neurocognition and greater dementia risk, although the mechanisms linking weight and neurocognition have yet to be adequately delineated. OBJECTIVE To examine metabolic mechanisms underlying the association between obesity and neurocognition. METHODS We conducted a secondary analysis of weight, neurocognition, and the potentially mediating role of metabolic and inflammatory biomarkers among 160 participants from the ENLIGHTEN trial of vascular cognitive impairment, no dementia (CIND). Neurocognition was assessed using a 45-minute assessment battery assessing Executive Function, Verbal and Visual Memory. We considered three metabolic biomarkers: insulin resistance (homeostatic model assessment [HOMA-IR]), plasma leptin, and insulin-like growth factor (IGF-1). Inflammation was assessed using C-reactive protein. Multiple regression analyses were used. RESULTS Participants included 160 sedentary older adults with CIND. Participants tended to be overweight or obese (mean BMI = 32.5 [SD = 4.8]). Women exhibited higher BMI (p = 0.043), CRP (p