Unraveling the link between frailty and Alzheimer’s disease biomarkers in patients with mild cognitive impairment

Alzheimer's disease (AD) can be identified through biomarkers of amyloid (A) and tau (T) pathology. Frailty, a measure of biological aging, could impact the association between AD neuropathology and its clinical manifestation. We aimed to investigate the relationship between frailty and AD biomarkers among people with mild cognitive impairment (MCI) attending a university memory clinic. Data were collected from a cohort of patients with MCI at the Memory Center of Geneva University Hospital (Switzerland). Frailty was assessed using a 35-item Frailty Index (FI). A and T positivity were determined through amyloid and tau PET or CSF analysis. Participants were divided into two subgroups: (i) A + T + (both amyloid and tau positive) and (ii) E/N (either A + or T + , neither A + nor T +), including all other combinations of A/T status. We first explored the correlation between FI, age, and education. Demographics, FI scores, and neuropsychological test results were then compared between these two groups. Logistic regression models, adjusted for age, sex, and education were used to examine the association between FI and AT positivity. One hundred twenty patients were included. FI was positively correlated with age and inversely with education. A + T + patients exhibited lower FI scores compared to E/N participants (0.13 ± 0.10 vs. 0.15 ± 0.08, p = 0.01). Logistic regressions found a negative association between FI and A + T + (OR 0.6, 95% CI 0.32-0.90; p = 0.02). Frailty is associated with a lower likelihood of AD biomarker positivity in patients with MCI. Frailty might reflect alternative pathophysiological mechanisms contributing to cognitive impairment.