Frailty begins to accelerate 4 to 9 years before dementia onset and may help identify at-risk populations for prevention strategies.

A recent study published in JAMA Neurology investigated the relationship between frailty and the risk of dementia by analyzing frailty trajectories in older adults before the onset of dementia.

Using data from multiple large cohort studies, the researchers assessed how frailty levels change over time. They aimed to identify whether frailty could be a potential early marker for dementia risk and a target for preventative interventions.

Background

Dementia is a natural process in aging populations and stems from diverse age-related brain pathologies that suggest that aging itself is a primary factor influencing the risk of dementia. However, identifying markers that reflect biological age and predict the onset of dementia could improve prevention and treatment efforts.

Frailty, characterized by physical vulnerability due to accumulated deficits in health, has emerged as a promising indicator of biological age and risk of dementia. Studies have shown that higher frailty scores align with increased dementia risk, independent of age. However, while physical and social factors such as exercise and nutrition are known to affect frailty, the relationship between frailty and dementia remains poorly understood.

Moreover, potential reverse causality — the possibility that frailty may both influence and be influenced by impending dementia — further complicates this association. However, understanding whether frailty levels increase before the onset of dementia and how these changes impact dementia risk could help formulate more effective interventions.

About the study

The present study used data from four major cohort studies, which included the English Longitudinal Study of Ageing (ELSA), Rush Memory and Aging Project (MAP), Health and Retirement Study (HRS), and National Alzheimer Coordinating Center (NACC), to examine whether frailty was a potential early indicator of dementia. Each study provided longitudinal data on older adults above the age of 60, none of whom had cognitive impairments at baseline.

Dementia diagnoses were determined through clinical assessments, cognitive tests, or reports from caregivers or participants. Frailty was measured using a frailty index, which is a cumulative score derived from health deficits across physiological systems. These deficits included a range of health issues, with each participant’s frailty score reflecting the number of deficits present.

Only participants with complete frailty data on at least 30 deficits were included. The study conducted follow-ups until participants developed dementia or until the study ended, with follow-up periods varying across cohorts.

Additionally, the researchers used Bayesian generalized linear mixed models to track changes in frailty over time relative to the onset of dementia. These models incorporated factors such as age, sex, education, and ethnicity. Potential non-linear changes in frailty were modeled, and Cox proportional-hazards models were used to examine the association between frailty and the risk of dementia. For the statistical analyses, the participants were also separated into groups based on when the frailty levels were measured relative to the onset of dementia.

Results

The results indicated that frailty increases significantly in the years preceding the onset of dementia. Frailty levels increased notably in the four to nine years preceding a diagnosis of dementia, with the association varying across cohorts. Frailty scores were consistently higher in individuals who later developed dementia as compared to those who remained free of dementia, even when frailty was measured years before the diagnosis.

Furthermore, in both men and women, a higher baseline frailty score was linked to an elevated risk of dementia, with each increase in the frailty index score indicating a progressively greater dementia risk. This association remained significant even after controlling for baseline demographic variables. The study also found that women generally had higher frailty scores than men in the years preceding dementia.

Additionally, the hazard ratios for frailty index scores showed that higher levels of frailty increased the risk of dementia across all datasets, with the strongest associations being observed in the NACC cohort and the weakest in HRS. Moreover, frailty remained a significant predictor of dementia even when the measurement periods were extended or deficits associated with dementia risk were removed from frailty calculations in the sensitivity analyses.

Conclusions

Overall, the study found that frailty could be an effective indicator for identifying individuals at high risk for dementia. The findings indicated that frailty is strongly linked to dementia risk, with significant increases in frailty occurring years before the onset of dementia.

These results supported the potential use of frailty measurements in identifying at-risk individuals and highlighted its value in targeted prevention strategies and recruitments for clinical trials on dementia.