according to research published online ahead of print Jan. 17 in Lancet Neurology. Data suggest that frailty reduces the threshold for Alzheimer’s disease pathology to cause cognitive decline. Frailty also may contribute to other mechanisms that cause dementia, such as inflammation and immunosenescence, said the investigators.
“While more research is needed, 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,” said Professor
More susceptible to dementia?
The presence of amyloid plaques and neurofibrillary tangles is not a sufficient condition for the clinical expression of dementia. Some patients with a high degree of Alzheimer’s disease pathology have no apparent cognitive decline. Other factors therefore may modify the relationship between pathology and dementia.
Most people who develop Alzheimer’s disease dementia are older than 65 years, and many of these patients are frail. Frailty is understood as a decreased physiologic reserve and an increased risk for adverse health outcomes. Dr. Rockwood and his colleagues hypothesized that frailty moderates the clinical expression of dementia in relation to Alzheimer’s disease pathology.
To test their hypothesis, the investigators performed a cross-sectional analysis of data from thewhich collects clinical and pathologic data from adults older than 59 years without dementia at baseline who live in Illinois. Since 1997, participants have undergone annual clinical and neuropsychological evaluations, and the cohort has been followed for 21 years. For their analysis, Dr. Rockwood and his colleagues included participants without dementia or with Alzheimer’s dementia at their last clinical assessment. Eligible participants had died, and complete autopsy data were available for them.
The researchers measured Alzheimer’s disease pathology using a summary measure of neurofibrillary tangles and neuritic and diffuse plaques. Clinical diagnoses of Alzheimer’s dementia were based on clinician consensus. Dr. Rockwood and his colleagues retrospectively created a 41-item frailty index from variables (e.g., symptoms, signs, comorbidities, and function) that were obtained at each clinical evaluation.
Logistic regression and moderation modeling allowed the investigators to evaluate relationships between Alzheimer’s disease pathology, frailty, and Alzheimer’s dementia. Dr. Rockwood and hus colleagues adjusted all analyses for age, sex, and education.
In all, 456 participants were included in the analysis. The sample’s mean age at death was 89.7 years, and 69% of participants were women. At participants’ last clinical assessment, 242 (53%) had possible or probable Alzheimer’s dementia.
The sample’s mean frailty index was 0.42. The median frailty index was 0.41, a value similar to the threshold commonly used to distinguish between moderate and severe frailty. People with high frailty index scores (i.e., 0.41 or greater) were older, had lower Mini-Mental State Examination scores, were more likely to have a diagnosis of dementia, and had a higher Braak stage than those with moderate or low frailty index scores.