Frailty may predict dementia risk years before onset, study finds

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

A recent study published in JAMA Neurology examined the relationship between frailty and dementia risk 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 determine whether frailty could be a potential early marker of dementia risk and a target for preventive interventions.

Background

Dementia is a natural process in the aging population and arises from several 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 health problems, has emerged as a promising indicator of biological age and dementia risk. Studies have shown that higher frailty scores correspond to an increased risk of dementia, regardless of age. Although physical and social factors such as exercise and diet are known to influence frailty, the relationship between frailty and dementia remains poorly understood.

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

About the study

The current study used data from four large cohort studies, including the English Longitudinal Study of Aging (ELSA), the Rush Memory and Aging Project (MAP), the Health and Retirement Study (HRS), and the National Alzheimer’s Coordinating Center (NACC) , to investigate whether frailty was a possible early indicator of dementia. Each study provided longitudinal data on older adults over 60 years of age, none of whom had cognitive impairment at baseline.

Diagnoses of dementia were determined through clinical assessments, cognitive tests, or reports from caregivers or participants. Frailty was measured using a frailty index, a cumulative score derived from health deficits in physiological systems. These deficits included a range of health conditions, with each participant’s vulnerability 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 by cohort.

Additionally, the researchers used Bayesian generalized linear mixed models to track changes in frailty over time relative to the onset of dementia. These models include factors such as age, gender, 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 dementia risk. For the statistical analyses, participants were also divided into groups based on when frailty levels were measured in relation to the onset of dementia.

Results

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

Furthermore, in both men and women, a higher baseline frailty score was linked to an increased risk of dementia, with each increase in the frailty index score indicating an increasing risk of dementia. 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 leading up to dementia.

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

Conclusions

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

These results supported the potential use of frailty measures in identifying individuals at risk and underlined their value in targeted prevention strategies and recruitment for dementia clinical trials.