Frailty Tied to Future Dementia

Frailty — a measure of health deficits in multiple body systems — was tied to future risk of dementia, longitudinal data from four cohorts showed.

Across nearly 30,000 older adults in the U.S. and the U.K., frailty was positively associated with dementia, with adjusted hazard ratios (HRs) ranging from 1.18 (95% CI 1.13-1.24) to 1.73 (95% CI 1.57-1.92), according to David Ward, PhD, of the University of Queensland in Australia, and co-authors.

Trajectories of frailty increased more rapidly 4 to 9 years before dementia onset. Even before this acceleration, higher frailty levels were linked with increased dementia risk (HRs 1.18 to 1.43), the researchers reported in JAMA Neurology.

Frailty is an age-related health state in which multiple body systems lose resilience, leading to higher susceptibility to adverse health outcomes, Ward noted.

“By understanding and tracking frailty, healthcare professionals can get a fuller picture of a person’s dementia risk beyond just their chronological age,” he told MedPage Today. “This insight supports the idea that maintaining good health and function throughout life can potentially delay or prevent dementia onset, underscoring the importance of proactive health management.”

The findings may point to frailty as an early indicator of cognitive decline risk. “They suggest that routine frailty assessments in primary care could play a critical role in identifying individuals at risk long before significant cognitive symptoms emerge, paving the way for earlier intervention and support,” Ward said.

Frailty measurements also may help identify high-risk population groups to enroll in dementia prevention and treatment clinical trials, the researchers suggested.

To identify time relationships between frailty and incident dementia, Ward and colleagues assessed information from four prospective cohorts: the English Longitudinal Study of Aging, the Health and Retirement Study, the Rush Memory and Aging Project, and the NIH’s National Alzheimer’s Coordinating Center. Follow-up periods ranged from a median of 5 to 10 years. Data were collected from 1997 through 2024.

In total, 29,849 people over age 60 were included in the study; all had no cognitive impairment at baseline. Mean age was about 72 and 62% were women. Age, sex, education, and ethnicity were covariates in the analyses.

The degree of frailty for each participant was quantified using retrospectively calculated frailty index scores, which had been developed and validated in each cohort.

The scores assessed more than 50 possible health deficits, ranging from joint pain to atrial fibrillation to abnormal vision or hearing. Each 0.1 increase in frailty index score was equivalent to 4 to 5 additional health deficits.

“Each frailty index was adapted for our investigation by ensuring that deficits closely reflecting cognition were removed from their composition,” the researchers noted. “As frailty index scores represent the proportion of total health deficits of an individual, higher scores indicate the accumulation of more age-related health deficits and worse health.”

The study outcome was all-cause dementia. Over 257,963 person-years of follow-up, 3,154 cases of incident dementia emerged. Among those who developed dementia, frailty was higher in women than men.

Mechanisms linking frailty and cognition aren’t clear, the researchers noted. Rapidly rising frailty scores may represent an exhaustion of systemic reserves, making individuals more vulnerable to diseases that would otherwise be subclinical, they suggested. It’s possible that frailty precipitates dementia by accelerating age-related brain changes or that neurodegenerative processes hasten frailty, they added.

Because dementia has a preclinical period that could span up to 20 years, the study may include some degree of reverse causality, Ward and co-authors acknowledged. Some potentially relevant covariates like socioeconomic status were not included because they weren’t universally available. In addition, the analyses did not account for genetic risks, including APOE4 status.

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