Stage-Specific Relationship between Frailty and Cognitive Impairment in a Specialist Memory Clinic Setting

It is unclear if the complex relationship between physical frailty and cognition varies across the severity of cognitive impairment.

We therefore aimed to explore if there are stage-specific differences in the relationship between frailty and cognitive impairment.

Cross-sectional study.

A specialist Memory Clinic setting.

Mild cognitive impairment (MCI) and mild-moderate Alzheimer's disease (AD) community-dwelling subjects.

We obtained data on demographics, multimorbidity, cognition-related measures, nutrition, neuroimaging measures, muscle mass, Vitamin D level, apolipoprotein - e (APOE) status and physical performance measures. Frailty measures of gait speed, hand grip strength, question on exhausation and weight loss, classified subjects according to the Buchmann criteria into non-frail and frail categories.

Forty-five MCI, 64 mild AD and 13 moderate AD subjects (total n=122) were studied. The prevalence of frailty for MCI, mild AD and moderate AD was 35.6%, 21.9% and 46.2% respectively, indicating a u-shaped trend. Significant differences were noted in fatigue, grip strength and gait speed frailty sub-items. Significant correlation of frailty with cognition were noted in mild-moderate AD (Spearman's coefficient 0.26, p<0.05) but not in MCI (0.01, p=0.6). No other differences in multimorbidity, Vitamin D, APOE, nutritional measures, white matter lesions were observed. Sarcopenia interestingly had an inverse stage-specific relationship unlike frailty.

Our results suggest a U-shaped relationship between frailty and cognition, characterized by initial dissociation with cognitive impairment and subsequent convergence at later stages. Future studies incorporating immune markers and endocrine pathways with longitudinal follow-up could potentially elucidate intermediary mechanisms in the frailty cascade.