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Frailty and prognosis in Alzheimer's disease

In this Swedish register-based cohort study, frailty was associated with institutionalisation and survival outcomes, but not with cognitive decline rate.

  • Xin Xia, PhD; Maria Eriksdotter, MD; Henrik Zetterberg, MD; Silke Kern, MD; Tobias Skillbäck, PhD; Marco Toccaceli Blasi, MD; et al.

  • December 17, 2025

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We searched for relevant studies in PubMed with the search term “frailty” AND “Alzheimer’s disease” AND (“prognosis” OR “cognitive decline” OR “cognitive deterioration” OR “institutionalization” OR “nursing home” OR “mortality” OR “survival”) until Sept 8, 2025, without specifying an inception date. We identified two relevant cohort studies on the associations between frailty and the prognosis of Alzheimer’s disease. Alzheimer’s disease in these studies was not confirmed with biomarker testing. These studies suggest that frailty was associated with a higher mortality rate and faster cognitive decline.

This Swedish register-based cohort study found that frailty, measured by the frailty index, was associated with a higher hazard of future institutionalisation and mortality. Frailty was associated with 1·3-year shorter overall survival and 1·0 years fewer non-institutionalised life-years. However, frailty was not associated with cognitive decline rate, whereas cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease were significantly associated with cognitive decline rate. In addition, frailty did not modify the associations between Alzheimer’s disease CSF biomarkers and cognitive decline rate.

Frailty can inform the prognosis of Alzheimer’s disease, especially institutionalisation and survival. Measuring frailty can help identify individuals with decreased physical and mental capacities in those with CSF biomarker-confirmed Alzheimer’s disease. In addition, the frailty index can be a useful instrument for using real-world data to conduct post-authorisation safety and effectiveness evaluations of medicines in individuals with Alzheimer’s disease who were frail, including emerging disease-modifying treatments.

Source: The Lancet Healthy Longevity

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