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Alzheimer’s Disease Driver: Overweight or Underweight?

By Karen Appold

A recent study showed that middle-aged adults who are overweight are more likely to develop Alzheimer’s disease (AD) decades later than individuals at normal weight. However, research has also revealed that people in the earliest stages of AD are more likely to have a lower body mass index (BMI).

“While the results may seem conflicting, we think that both assessments are accurate,” says study author Jeffrey Burns, MD, MS, associate director of the University of Kansas Alzheimer's Disease Center. “Our interpretation is that on one hand being overweight increases the risk of having Alzheimer’s disease, and in the earliest stages of this disease, weight loss can occur.

“Weight loss does not always occur because someone forgets to eat; rather our findings suggest that there is a disease process that is ongoing,” Burns continues. “It is common for older people to lose weight, and many factors can drive it.”

The study, published in the November 22, 2011, edition of Neurology, showed that being overweight in midlife has been linked to a long-term risk of dementia and being underweight later in life has been more strongly linked with AD. “What our studies suggest is that being underweight is a result of the disease rather than a risk,” Burns says.

“But risk factors during midlife—for example, metabolic syndrome, overweight, and high blood pressure—might not be risk factors in late life,” says Claudia H. Kawas, MD, a professor at the University of California, Irvine. Being overweight, for example, appears to be a risk factor if it occurs in midlife, but it does not clearly have the same effects in studies of people in late life (80s and 90s). Similarly, there is evidence that hypertension in midlife is a risk factor for dementia, but in late life it may even be a protective factor.

Study Details

The study examined 506 people with advanced brain imaging techniques and analyzed cerebrospinal fluid to look for biomarkers for AD, which can be present years before initial symptoms. Participants included people without memory problems, people with mild cognitive impairment or mild memory problems, and people with AD.

The study found that in individuals with no memory or thinking problems or with no mild cognitive impairment, those with Alzheimer’s biomarkers were more likely to have a lower BMI than those who did not have the biomarkers.

For example, 85% of people with mild cognitive impairment who had a BMI below 25 had in their brains signs of the beta-amyloid plaques that are a hallmark of the disease compared with 48% of those with mild cognitive impairment who were overweight. This relationship was also found in people with no memory or thinking problems.

Kaycee M. Sink, MD, an associate professor of geriatrics and gerontology at Wake Forest Baptist Medical Center, notes that data also suggest it is not total weight, or even BMI per se, that increases risk but rather central obesity. In other words, people with an apple shape are at a higher risk of Alzheimer’s than people with a pear shape, even if they have the same BMI.

Metabolic Changes

Study results suggest AD brain changes are associated with systemic metabolic changes in the very earliest phases of the disease. “This might be due to damage to the hypothalamus, which plays a role in regulating energy metabolism and food intake,” Burns says.

The components of metabolic syndrome include impaired glucose tolerance, abdominal or central obesity, hypertension, high triglycerides, and low HDL cholesterol. “There is increasing evidence that individual components as well as the syndrome as a whole increases the risk of developing Alzheimer’s disease,” Sink says. “The reasons why metabolic syndrome is increasing the risk of Alzheimer’s disease are likely related to inflammation and vascular disease, although others are being actively explored.”

Burns notes that genetics as well as environmental factors, such as diet, exercise, and cardiovascular health (ie, hypertension, stroke, cholesterol) also play a role in determining a patient’s risk of developing AD. “It is probably a combination of genetic factors and lifestyle factors that ultimately puts someone at risk for Alzheimer’s disease.” A history of traumatic brain injury has also been shown to put people at a higher risk of developing the disease.

“Further studies should investigate whether this relationship reflects a systemic response to an unrecognized disease or a long-standing trait that predisposes a person to developing the disease,” Burns says.

Advising Patients

Physicians should counsel patients at all ages about healthy body weight, controlling metabolic risk factors, not smoking, etc. “In older adults, controversy exists regarding counseling patients to specifically lose weight, but if an older adult is losing weight unexpectedly—regardless of starting weight—an evaluation should be undertaken,” Sink says. In addition to conditions commonly associated with unintentional weight loss (eg, cancer, hyperthyroidism), providers should also consider early memory loss.

With regard to encouraging weight loss for older patients who are obese, opinions are divided. Some experts are against encouraging weight loss in older adults while others believe that benefits on metabolic parameters, joint disease, and other symptoms outweigh risks of weight loss. “That said, evidence is mounting that fitness is more important than weight in several outcomes, cognition included,” Sink says. “I recommend trying to get sedentary older adults to be more active, such as walking several times per week. Increasing physical activity is likely to do a lot more for helping to reduce risk of cognitive decline than losing weight.”

Burns advises providers to remain alert for changes. “If someone exhibits memory changes, that can be an early sign of dementia. A persistent change, even if minor, can be a red flag that changes in the brain may be driving the symptoms,” he says.

— Karen Appold is a freelance medical writer in Royersford, Pennsylvania.