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Abstract

To investigate whether total and/or regional adiposity measured by anthropometry and radiographic studies influences cognitive decline in older adults and whether this association is explained by hormones and inflammatory factors known to be secreted by adipose tissue. Prospective cohort study. Two clinical centers. Three thousand fifty-four elderly individuals enrolled in the Health ABC Study. Adiposity measures included body mass index, waist circumference, sagittal diameter, total fat mass by dual-energy x-ray absorptiometry, and subcutaneous and visceral fat by abdominal computed tomography. We examined the association between baseline body fat measures and change in Modified Mini-Mental State Examination (3MS) score, sequentially adjusting for confounding and mediating variables, including comorbid diseases, adipocytokines, and sex hormones. Main Outcome Measure Scores from the 3MS, administered at the first, third, fifth, and eighth annual clinical examinations. All baseline adiposity measures varied significantly by sex. In mixed-effects models, the association between total and regional adiposity and change in 3MS score varied significantly by sex, with the highest adiposity tertile being associated with greater cognitive declines in men (for each adiposity measure, P < .05) but not in women (for interaction, P < .05). Total fat mass was significantly associated with greater change in 3MS scores among men (lowest tertile, -1.6; middle tertile, -2.2; highest tertile, -2.7; P = .006), even after adjusting for mediators. Higher levels of all adiposity measures were associated with worsening cognitive function in men after controlling for metabolic disorders, adipocytokines, and sex hormone levels. Conversely, there was no association between adiposity and cognitive change in women.