Frailty May Increase Susceptibility to Alzheimer’s Disease

February 21, 2019

Older adults who are frail are at increased risk of developing Alzheimer’s disease, a new report found. Frailty increased the risk of Alzheimer’s disease even in those whose brains showed few signs of damage from the illness. And in those who had brain changes typical of Alzheimer’s disease but who were in robust health rather than frail, good overall health seemed to protect against the development of memory loss and other symptoms of dementia, the study found.

Frailty, which is marked by weakness and fatigue, is common in the elderly. It is often accompanied by a host of problems, including joint and heart ailments, bone thinning, and difficulty with mobility and everyday tasks like preparing meals. The findings suggest that frailty not only diminishes the body’s physical reserves. It may also diminish the brain’s ability to ward off the brain damage caused by Alzheimer’s disease.

“By reducing an individual’s physiological reserve, frailty could trigger the clinical expression of dementia when it might remain asymptomatic in someone who is not frail,” said Dr. Kenneth Rockwood from Nova Scotia Health Authority and Dalhousie University in Canada, who led the study. “This indicates that a ‘frail brain’ might be more susceptible to neurological problems like dementia as it is less able to cope with the pathological burden.”

“Given that frailty is potentially reversible, it is possible that helping people to maintain function and independence in later life could reduce both dementia risk and the severity of debilitating symptoms common in this disease,” Dr. Rockwood added.

The findings, published in the journal Lancet Neurology, underscore the complexity of Alzheimer’s disease. Earlier research had shown that some people who have lots of beta-amyloid plaques in the brain, a hallmark of Alzheimer’s disease, exhibit only limited symptoms of the disease. Others with few plaques, on the other hand, may have a high degree of memory impairment. Frail physical health, which predisposes to a number of illnesses, may explain some of these discrepancies.

For the study, researchers looked at 456 older men and women who were 60 or older and living in Illinois when they enrolled in a study called the Rush Memory and Aging Project. None had Alzheimer’s at the start of the study, in 1997, and they were given regular physical exams and cognitive assessments over the ensuing decades. In January 2017, over half were eventually given a “possible or probable Alzheimer’s dementia” diagnosis. When these study participants died, their brains underwent autopsy.

Overall, 35 participants, or about 8 percent, had substantial Alzheimer’s disease-related brain changes without having been diagnosed with dementia, and 50, or 11 percent, had Alzheimer’s dementia but had little disease-related brain changes. The analysis found that frailty and Alzheimer’s disease-related brain changes each independently contribute to dementia status. Indeed, among people with little disease-related brain changes, 65 percent of patients who had high frailty had Alzheimer’s dementia versus 5 percent for those with low frailty.

“While frailty is likely to reduce the threshold for Alzheimer’s disease-related brain changes to cause cognitive decline, it probably also contributes to other mechanisms in the body that give rise to dementia, weakening the direct link between Alzheimer’s disease-related brain changes and dementia,” Dr. Rockwood said.

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Marc Flajolet, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Source: Lindsay MK Wallace, Olga Theou, Judith Godin, et al: “Investigation of Frailty as a Moderator of the Relationship Between Neuropathology and Dementia in Alzheimer’s Disease: A Cross-Sectional Analysis of Data from the Rush Memory and Aging Project.” Lancet Neurology, Feb. 1, 2019


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