medwireNews: Frailty is a meaningful marker of biological age and dementia risk and could help identify high-risk individuals for prevention and treatment strategies, suggests a study published in JAMA Neurology.
The investigators explored the temporal relationship between frailty and dementia using data collected between 1997 and 2024 from four prospective cohort studies, namely the English Longitudinal Study of Ageing, the Health and Retirement Study, the Rush Memory and Aging Project, and the National Alzheimer Coordinating Center.
The studies included individuals over the age of 60 years who were cognitively unimpaired and lived in retirement communities or were included in national-level surveys or clinic-based cohorts.
In all, 29,849 participants (mean age 71.6 years; 62% women; 85% White) with a total of 257,963 person–years of follow-up were assessed. Their mean frailty index scores ranged from 0.09–0.17, where a score of 0.12–0.24 signifies mild frailty and a score of 0.36 and above severe frailty.
There were 3154 cases of incident dementia and applying mixed regression models to composite frailty index scores, based on at least 30 health deficits and adapted to remove deficits closely resembling cognition, showed that the scores increased in the years before dementia.
Frailty scores among patients who developed dementia were consistently higher than those of individuals who did not in the 8 to 20 years before dementia onset, after taking into account age, sex, education, and ethnicity. Women who developed dementia had frailty scores that were, on average, 16.2% to 20.9% higher than those of their male counterparts.
Moreover, the researchers found that the increase in frailty scores significantly diverged between patients who did and did not develop dementia, indicating an acceleration, at between 4 and 9 years prior to dementia onset in both men and women.
At the point of dementia detection, frailty scores were 0.4 to 0.21 points higher in participants with than without dementia and each 0.1-point increase (equating to 4–5 additional health deficits) was associated with a significant 18–73% increased risk for dementia.
The association between frailty and dementia risk remained even for participants whose baseline frailty occurred before the identified acceleration period, albeit at a lower likelihood of between 18% and 43%, the team remarks.
David Ward (The University of Queensland, Woolloongabba, Australia) and colleagues say that “the findings from our analyses align with the position that frailty could be a strong dementia risk factor,” although they note that the lack of a randomized design may have contributed to reverse causality in their study, given the 20-year preclinical dementia phase.
The investigators conclude: “These results offer insight into the natural course of declining health in the subclinical stages of neurodegenerative diseases, position frailty index scores as a measure effective in identifying high-risk individuals for inclusion into treatment and prevention trials for dementia, and support the notion that frailty may serve as an upstream dementia risk factor.”
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