# Prevalence of frailty and its association with cognition in preclinical Alzheimer’s disease: a cross-sectional analysis of baseline data from the A4 study

## TL;DR

This study finds that frailty is common in preclinical Alzheimer's and linked to worse cognition, but does not affect the relationship between amyloid levels and cognition.

## Contribution

The study introduces two models of a frailty index and examines their associations with cognition in preclinical Alzheimer's disease.

## Key findings

- Aβ+ participants were more likely to be frail compared to Aβ− participants.
- Frail participants had lower cognitive scores compared to non-frail participants.
- Frailty did not moderate the relationship between amyloid status and cognition.

## Abstract

The prevalence and role of frailty in preclinical Alzheimer’s disease (AD) is unclear.

Cross-sectional analyses of pre-randomization data from the Anti-Amyloid Treatment in Asymptomatic AD (A4) study were analysed to derive two models of a frailty index (FI)—full [FI-Full] and cognitive variables removed [FI-CVR]. The prevalence of frailty (FI > 0.25) according to amyloid status (Aβ+/−), and the association of frailty and cognition (determined by the Preclinical Alzheimer Cognitive Composite (PACC) score) and whether frailty moderates the relationship between amyloid status and cognition was assessed, adjusting for age, sex and education.

Four thousand four hundred eighty-six participants were included (mean age 71.3 ± 4.7 years, 30% participants Aβ+, 59% female). The prevalence of frailty in preclinical AD was 22% (or 44% when cognitive variables were removed from the FI). Using either FI model, in adjusted analyses, Aβ+ participants were more likely to be frail compared to Aβ− [FI-Full—Odds ratio (OR) 1.43 95% confidence interval (CI) 1.20–1.71, P < .001; FI-CVR—OR 1.21 95% CI 1.05–1.40, P < .008]. Frail participants had lower PACC scores compared to non-frail participants, on average (FI-Full—PACC score −0.58 95% CI −0.76 to −0.40, P < .001; FI-CVR—PACC score −0.26 95% CI −0.40 to −0.12, P < .001). Frailty did not influence the relationship between Aβ status and cognition.

In a cohort screened for a preclinical AD trial, elevated Aβ levels were associated with frailty and frailty was associated with reduced cognitive performance independent of elevated Aβ levels. These associations, and whether or not frailty is associated with longitudinal cognitive decline independent of Aβ status, warrant further study.