Alzheimer's Effects on Brain Linked to Physical Frailty

By Crystal Phend
CHICAGO, 13 aug 2008-- Changes in brain structures typical of Alzheimer's disease may be related to physical frailty late in life, researchers found.
The degree of Alzheimer's pathology seen at brain autopsy explained about 4% of variance in physical frailty (P=0.001), reported Aron S. Buchman, M.D., of Rush Medical Center here, and colleagues, in the Aug. 12 issue of Neurology.
In their analysis of patients from a large, longitudinal study of aging, the association was similar for demented and nondemented patients alike and persisted after adjustment for cardiovascular risk and other factors.
A previous analysis of the study linked frailty to incident Alzheimer's disease. The new findings suggest that "frailty may be a noncognitive manifestation of Alzheimer's pathology that can manifest before dementia," Dr. Buchman's group said.
This should come as no surprise, they said. Other studies have shown that individual components of frailty, such as motor function, grip strength, and gait speed predict Alzheimer's.
Accumulation of the plaques and tangles seen in the brain of Alzheimer's disease patients may impair neural systems that handle the planning and monitoring of even simple movements, the researchers speculated.
Another possible explanation for the link between Alzheimer's pathology and frailty is that both share a common cause, they said.
The researchers analyzed brain pathology from 165 consecutive autopsies of patients who died while enrolled in the Rush Memory and Aging Project, a longitudinal study of patients initially free of dementia.
Men and women in the analysis were an average 84.6 years old at baseline. They were followed annually until death at an average age of 88.1 with their last assessment of frailty about six months before death, on average.
Among them, 35.8% had been diagnosed with dementia by the time of death.
All but three of the patients had some degree of the plaques and tangles associated with Alzheimer's disease. The summary scores for this brain pathology ranged from 0 to a high of 3.2 (mean 0.7).
Patients with greater Alzheimer's pathology had poorer physical performance on the composite aspects of frailty (P=0.001).
Among the components of frailty, grip strength and body mass index were significantly linked to Alzheimer's brain changes (P=0.019 and P=0.030, respectively). Although there was a trend for an association with gait (P=0.071), fatigue was not a factor significantly linked to Alzheimer's pathology (P=0.627).
Participants in the 90th percentile for global Alzheimer's pathology (1.6 units) were about twice as frail as those in the 10th percentile (0.2 units).
Together, age, sex, and education explained 18% of the variance between individuals in frailty. Alzheimer's disease-related brain pathology accounted for another 4% of the variance.
Among other common brain pathologies, 34.6% of patients had macroscopic cerebral infarcts and 14.3% had Lewy body pathology, but neither was associated with frailty (P=0.678).
Although all three pathologies were included in a single analysis, Alzheimer's disease pathology was the only one associated with frailty (P<0.001).
Dementia patients were frailer and had more Alzheimer's pathology than those without dementia (both P<0.001), but the interaction between these factors was not significant (P=0.976).
The association between frailty and Alzheimer's remained significant after controlling for a full range of potential confounders, including age, sex, education, physical activity, parkinsonian signs, pulmonary function, vascular risk factors, vascular disease burden, history of joint pain or falls, and use of antipsychotic or antihypertensive medications.
The study was limited by inclusion of a cohort of older patients that differed from those in the general population in education, socioeconomic status, and lifestyle.
The study was supported by National Institute on Aging grants, the Illinois Department of Public Health, and the Robert C. Borwell Endowment Fund. The researchers reported no conflicts of interest.
Primary source: NeurologySource reference:Buchman AS, et al "Physical frailty in older persons is associated with Alzheimer disease pathology" Neurology 2008; 71: 499-504.