Frailty impacts susceptibility to dementia
Study findings published in The Lancet Neurology indicated that frailty makes older adults more susceptible to Alzheimer’s dementia and moderates the effects of Alzheimer’s disease-related brain changes on dementia symptoms.
Frailty and Alzheimer’s dementia have many risk factors and clinical features in common, such as age, inflammation, functional impairment and atypical illness presentation, Lindsay M.K. Wallace, MSc, from Nova Scotia Health Authority, and the department of medicine, Dalhousie University, Halifax, Nova Scotia, and colleagues explained.
“The link between frailty and Alzheimer’s dementia has been shown both in clinical and epidemiological settings, but less so using neuropathological studies,” they wrote. “So far, such studies assessing Alzheimer’s disease pathology have been restricted to the phenotypic definition of frailty and none has examined the potential for frailty to moderate the relationship between Alzheimer’s disease pathology and dementia.”
Researchers conducted a cross-sectional analysis of data from participants enrolled in a clinical–pathological cohort study of adults aged 60 years and older without known dementia at baseline to examine whether frailty moderates the relationship between Alzheimer’s disease pathology and Alzheimer’s dementia. Participants underwent neuropsychological and clinical evaluations annually. Analyses were adjusted for age, sex and education.
Of 456 participants, 242 (53%) had a diagnosis of possible or probable Alzheimer’s dementia at their last clinical assessment. Wallace and colleagues found a significant interaction between frailty and Alzheimer’s disease pathology (OR = 0.73; 95% CI, 0.57-0.94). Analysis revealed that frailty (OR = 1.76; 95% CI, 1.54-2.02) and Alzheimer’s disease pathology (OR = 4.81; 95% CI, 3.31-7.01) were independently linked to dementia status. After adding the frailty index to the model with Alzheimer’s disease pathology, the fit improved significantly, according to the results.
Moderation analyses showed that the connection between Alzheimer’s disease pathology and dementia status differed by frailty level. Participants with a lower frailty score were better able to tolerate Alzheimer’s disease pathology, while those with higher scores were more likely to have more Alzheimer’s disease pathology and for it to be expressed as dementia.
“Our results suggest that dementia expression has several causes, and a single mechanism is unlikely to explain the diverse expressions that occur in the people who most often develop dementia: those who are older and have several comorbidities,” Wallace and colleagues wrote.
“Individuals with even a low level of Alzheimer’s disease pathology might be at risk for dementia if they have high amounts of frailty,” they continued. “This factor contributes to an emerging conceptualization of dementia, and particularly Alzheimer’s disease, as a complex disease of ageing rather than as a single disease entity marked by genetic risk or the deposition of a particular protein.”
Disclosures: Wallace reports personal fees from DGI Clinical. Please see the study for all other authors’ relevant financial disclosures.