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High BMI in Early-Old Age Tied to Brain Thinning in Later-Life

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Obesity in midlife has been associated with a higher risk for dementia. Yet, the underlying mechanisms behind how obesity may affect brain aging is unclear. Now, emerging evidence points to two predictors associated with brain thinning in early-old age: greater body mass index (BMI) and waist circumference, according to a study published in the July 24 online edition of Neurology.

For overweight people, every unit increase in BMI was associated with a 0.098 millimeter (mm) thinner cortex, and for obese people, a 0.207 mm thinner cortex, compared with people with normal weight. A bigger waist was also associated with a thinner cortex.

Previous research has tied cortical thickness to a higher risk of Alzheimer's disease (AD).

The researchers, led by Michelle R. Caunca, PhD, Medical Scientist Training Program, University of Miami Miller School of Medicine in Florida, emphasized that their findings support the American Heart Association/American Stroke Association's proposed guidelines for optimal brain health that recommends a BMI under 25. The data also implied that "obesity, especially in those < 65 years of age and in Hispanic/Latino patients, may damage gray matter structure [a predictor of AD] specifically," they wrote.

Dr. Caunca and her colleagues examined associations between measures of obesity in middle to early-old age with later-life MRI brain aging markers using data from 1,289 participants enrolled in the Northern Manhattan MRI Sub-Study (NOMAS), an ongoing longitudinal cohort study of diverse, stroke-free older adults. The mean age of participants was 64 years old. Over half of participants were women and two-thirds were Hispanic/Latino.

Baseline assessments included BMI, waist circumference, waist-to-hip ratio, and plasma adiponectin levels. A BMI of 25 to 25.9 was defined as "overweight, and obesity as a BMI of 30 or higher.

After baseline, the participants underwent brain MRI for an average of six years. Researchers examined MRI markers of brain aging, including total cerebral volume, which includes gray and white matter, total intracranial volume, white matter hyperintensity volume, and subclinical brain infarct. Data for cortical thickness was available for a subsample of 947 participants.

A total of 346 participants had a BMI of less than 25; 571 had a BMI of 25 to 30, and 372 had a BMI of 30 or higher. The average waist circumference was 33 inches for the normal  weight group (comprising 54 percent women); 36 inches for the overweight group (comprising 56 percent women); and 41 percent (comprising 73 percent women) for the obese group.

After adjusting for demographic and vascular risk factors, the findings showed obesity was associated with smaller cortical thickness, compared with reference weight (BMI beta −0.089; 95% CI, −0.153 to −0.025; p< .05). Greater waist circumference was also associated with a thinner cortex (WC beta −0.103, 95% CI, −0.169 to −0.037; p< .05) in the fully adjusted model.

The researchers noted the risks for obesity differed by minority groups and gender. For example, greater BMI and smaller total intracranial volume were notable among both Hispanics/Latinos and non-Hispanic blacks, but the results were not of statistical significance for the latter.

For men, greater central obesity, which is defined by waist circumference, was related to a greater odds ratio of subclinical brain infarct, but not for women.

The researchers acknowledged there is a "greater burden of obesity and dementia in minority populations," yet many similar studies have been conducted in predominately non-Hispanic white participants.

They concluded further research is needed to elucidate the casual relationships between greater BMI, obesity, and greater waist circumference and reduced gray matter and to explore the associations with specific brain regions.

The National Institute of Neurological Disorders and Stroke and the Evelyn F. McKnight Brain institute funded the study.

Dr. Caunca reported no relevant disclosures. Co-authors reported relationships with Novartis Pharmaceuticals, BioTelemetry/CardioNet, Bristol-Myers Squibb-Pfizer Partnership, Boehringer Ingelheim, Daiichi-Sankyo, Janssen Pharmaceuticals, Sanofi-Regeneron Partnership, diaDexus, Inc., Organon, Hi-Tech, American Heart Association/American Stroke Association, and UpToDate.

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Caunca M, Gardener H, Simonetto M, et al. Measures of obesity are associated with MRI markers of brain aging: The Northern Manhattan Study. Neurology 2019; Epub 2019 Jul 24.