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

Abstract

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 WHRstratified 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.

Glycemic Dysregulations Are Associated With Worsening Cognitive Function in Older Participants at High Risk of Cardiovascular Disease: Two-Year Follow-up in the PREDIMED-Plus Study

“…In our study, no associations between HbA 1c levels and changes in cognitive function were observed in participants without diabetes (data not shown). Nevertheless, when HbA 1c was measured as a continuous variable, we found negative associations between high baseline values in HbA 1c levels and all the cognitive tests measured, except in the case of the CDT and the DSTs, thus aligning with findings from recent studies (34,36).…”

“…Longitudinal studies linking insulin resistance, as measured by HOMA-IR, and cognitive decline have shown discrepancies. In an older U.S. population with 8 years of follow-up, baseline HOMA-IR was not associated with changes in global cognitive function (36). However, in surviving patients with coronary heart disease, baseline HOMA-IR was associated with subsequent poorer cognitive performance on the composite cognitive score over 15 years (37).…”

Predictors of attrition in a longitudinal population-based study of aging

“…In such analyses, attrition is not treated as missing completely at random or non-informative; instead, covariates are used to model attrition and incorporate this into the main model of cognitive impairment or incident dementia (joint modeling) or take the method that has taken informative dropout into model specification (competing risks modeling). Other approaches via propensity score modeling (Dorsett, 2010;Ganguli et al, 2015;Wolinsky et al, 2010) and inverse probability weighting (Daza et al, 2017;Ganguli et al, 2020) can be used to reform the original dataset via matching or weighting in accordance with non-response or attrition bias, thus allowing results to be generalized back to the original cohort. We caution that these post-hoc methods only help to minimize attrition bias and do not "magically" repair serious biases in the data.…”

Secondary Prevention of Dementia: Combining Risk Factors and Scalable Screening Technology

“…Marden, Mayeda ( 45 ) reported that each percentage point increase in HbA1c was associated with a 0.052 unit decrease on a custom memory score per decade even in individuals without clinical diabetes. In a population-based cohort study HbA1c of 6.2% or greater predicted faster cognitive decline in individuals aged between 65 and 88 even after adjusting for age, sex, education, and APOE ε4 status ( 46 ). A cross-sectional study of patients with T2D showed a non-linear association between HbA1c levels and cognitive function that indicated a bell-shaped relationship with low and high HbA1c levels affecting cognitive decline ( 47 ).…”