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Does Obesity Accelerate Brain Aging?

Does Obesity Accelerate Brain Aging?

Aging is associated with structural changes to the brain that increase the risk for dementia. These changes include the loss of brain volume, and damage to blood vessels in the brain. Cardiovascular and metabolic risk factors, such as obesity, high blood pressure (i.e. hypertension), and type 2 diabetes, can promote these age-related changes. Recent evidence suggests that women may be more sensitive to the effects of these cardiovascular and metabolic risk factors on brain structure and function during aging.

In an observational study involving 1,322 cognitively normal people over age 65 in South Korea, women with cardiovascular and metabolic risk factors were found to have faster rates of brain aging, while the rate of age-related brain loss was not significantly increased by these risk factors in men [1].

Obesity, as measured by increased levels of body fat, especially central belly fat, has been shown to be associated with lower brain volumes [2; 3]. While this relationship is seen in both men and women, different brain regions are preferentially affected in each sex. These differences may be important because it has been shown that brain volume loss in Alzheimer’s disease-associated regions, such as the hippocampus, is a stronger indicator of dementia progression than measures of total brain volume [4]. Women may be at a higher risk for obesity-induced damage in dementia-related brain regions.

High levels of body fat can induce small scale changes to the brain’s nerve fibers, and this microscopic damage may then set the stage for future damage which accelerates brain aging [5]. Women appear to be more vulnerable to changes that drive brain loss. A study found that relative to their lean counterparts, obese women had higher levels of degenerating axons and myelin, the primary components of nerve fibers [6]. While obese men also showed evidence of axon damage, their myelin was better preserved, so they were less vulnerable to accelerated brain aging.

Hypertension can lead to hardening of the arteries, which makes it harder for blood to flow throughout the body, and reduces the amount of blood flowing to the brain. The blood provides essential nutrients and oxygen, so the loss of blood flow can lead to damage to blood vessels and structural damage in the brain. High levels of vascular damage have been associated with increased risk for cognitive decline [7]. Hypertensive women were found to be more likely to experience reduced blood flow and higher rates of brain loss [1], which is consistent with the finding that women with hypertension have a 65 percent higher risk for dementia relative to hypertensive men [8].

Diabetes is an established metabolic risk factor for dementia, and women are at higher risk than men [9]. In the observational study, diabetes was more likely to promote brain shrinkage in women [1]. As with the other examined cardiovascular and metabolic risk factors, women appear to experience a higher degree of diabetes-related damage, which then fosters age-related brain loss.

These studies suggest that reducing cardiovascular and metabolic risk factors through maintaining a healthy weight and managing chronic conditions may be especially important for women to protect brain function and reduce dementia risk.

  1. Kim SE, Lee JS, Woo S et al. (2019) Sex-specific relationship of cardiometabolic syndrome with lower cortical thickness. Neurology 93, e1045-e1057.
  2. Arnoldussen IAC, Gustafson DR, Leijsen EMC et al. (2019) Dekkers IA, Jansen PR, Lamb HJ (2019) Obesity, Brain Volume, and White Matter Microstructure at MRI: A Cross-sectional UK Biobank Study. Radiology 291, 763-771.
  3. Wu A, Sharrett AR, Gottesman RF et al. (2019) Association of Brain Magnetic Resonance Imaging Signs With Cognitive Outcomes in Persons With Nonimpaired Cognition and Mild Cognitive Impairment. JAMA Network Open 2, e193359-e193359.
  4. Medic N, Kochunov P, Ziauddeen H et al. (2019) BMI-related cortical morphometry changes are associated with altered white matter structure. International Journal of Obesity 43, 523-532.
  5. Mueller K, Anwander A, Möller HE et al. (2011) Sex-dependent influences of obesity on cerebral white matter investigated by diffusion-tensor imaging. PloS one 6, e18544-e18544.
  6. Palta P, Sharrett AR, Wei J et al. (2019) Central Arterial Stiffness Is Associated With Structural Brain Damage and Poorer Cognitive Performance: The ARIC Study. J Am Heart Assoc 8, e011045-e011045.
  7. Gilsanz P, Mayeda ER, Glymour MM et al. (2017) Female sex, early-onset hypertension, and risk of dementia. Neurology 89, 1886-1893.
  8. Chatterjee S, Peters SAE, Woodward M et al. (2016) Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia. Diabetes Care 39, 300-307.

Betsy Mills, PhD, is Senior Program Manager of Aging and Alzheimer’s Prevention at the Alzheimer’s Drug Discovery Foundation. She earned her doctorate in neuroscience at Johns Hopkins University School of Medicine, where she studied the role of glial cells in the optic nerve and their contribution to neurodegeneration in glaucoma; and completed a Postdoctoral fellowship at the University of Michigan, where she worked to uncover genes that could promote retina regeneration. Dr. Mills has a strong passion for community outreach, and served as program presenter with the Michigan Great Lakes Chapter of the Alzheimer's Association to promote dementia awareness.

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