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.
Betsy Mills, PhD, is a member of the ADDF's Aging and Alzheimer's Prevention program. She critically evaluates the scientific evidence regarding prospective therapies to promote brain health and/or prevent Alzheimer's disease, and contributes to CognitiveVitality.org. Dr. Mills came to the ADDF from the University of Michigan, where she served as the grant writing manager for a clinical laboratory specializing in neuroautoimmune diseases. She also completed a Postdoctoral fellowship at the University of Michigan, where she worked to uncover genes that could promote retina regeneration. 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. She obtained her bachelor's degree in biology from the College of the Holy Cross. Dr. Mills has a strong passion for community outreach, and has served as program presenter with the Michigan Great Lakes Chapter of the Alzheimer's Association to promote dementia awareness.
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