Aging, Diabetes, Obesity, and Cognitive Decline: A Population‐Based Study

• Published in: Journal of the American Geriatrics Society (JAGS) Vol. 68; no. 5; pp. 991 - 998
• Main Authors: Ganguli, Mary, Beer, Joanne C., Zmuda, Joseph M., Ryan, Christopher M., Sullivan, Kevin J., Chang, Chung‐Chou H., Rao, R. Harsha
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.05.2020; Wiley Subscription Services, Inc
• Subjects: abdominal obesity; Adiponectin; Aged; Aged, 80 and over; Aging; Aging - blood; Apolipoprotein E; Apolipoprotein E4 - blood; Blood glucose; Blood pressure; Cognitive ability; Cognitive Dysfunction - blood; Cognitive Dysfunction - etiology; Cross-Sectional Studies; Diabetes; Diabetes mellitus; Diabetes Mellitus - blood; epidemiology; Female; Genotypes; Glucagon; Glycated Hemoglobin A - metabolism; Hemoglobin; Hip; Humans; Hyperglycemia; Hyperglycemia - blood; Hyperglycemia - complications; Insulin; Insulin resistance; Learning algorithms; Longitudinal Studies; Machine learning; Male; Obesity; Obesity, Abdominal - complications; Pennsylvania; Population; Population studies; Population-based studies; Prospective Studies; Regression analysis; Risk Factors; Pennsylvania; adiponectin; epidemiology; hyperglycemia; abdominal obesity
• ISSN: 0002-8614; 1532-5415; 1532-5415
• DOI: 10.1111/jgs.16321

BACKGROUND/OBJECTIVES To investigate potential mechanisms underlying the well‐established relationship of diabetes and obesity with cognitive decline, among older adults participating in a population‐based study. DESIGN/SETTING Ten‐year population‐based cohort study. PARTICIPANTS A total of 478 individuals aged 65 years and older. MEASUREMENTS We assayed fasting blood for markers of glycemia (glucose and hemoglobin A1c [HbA1c]), insulin resistance (IR) (insulin and homeostatic model assessment of IR), obesity (resistin, adiponectin, and glucagon‐like peptide‐1), and inflammation (C‐reactive protein). We modeled these indices as predictors of the slope of decline in global cognition, adjusting for age, sex, education, APOE*4 genotype, depressive symptoms, waist‐hip ratio (WHR), and systolic blood pressure, in multivariable regression analyses of the entire sample and stratified by sex‐specific median WHR. We then conducted WHR‐stratified machine‐learning (Classification and Regression Tree [CART]) analyses of the same variables. RESULTS In multivariable regression analyses, in the entire sample, HbA1c was significantly associated with cognitive decline. After stratifying by median WHR, HbA1c remained associated with cognitive decline in those with higher WHR. No metabolic indices were associated with cognitive decline in those with lower WHR. Cross‐validated WHR‐stratified CART analyses selected no predictors in participants older than 87 to 88 years. Faster cognitive decline was associated, in lower WHR participants younger than 87 years, with adiponectin of 11 or greater; and in higher WHR participants younger than 88 years, with HbA1c of 6.2% or greater. CONCLUSIONS Our population‐based data suggest that, in individuals younger than 88 years with central obesity, even modest degrees of hyperglycemia might independently predispose to faster cognitive decline. In contrast, among those younger than 87 years without central obesity, adiponectin may be a novel independent risk factor for cognitive decline. J Am Geriatr Soc 68:991–998, 2020