Association between frailty and the progression trajectories of stroke and dementia comorbidity: insights from observational and genetic analyses.

Background: The relationship between frailty and the progression trajectories of stroke-dementia comorbidity remains inconclusive. This study aimed to determine whether there are associations between frailty and the progression trajectories of stroke-dementia comorbidity, including the transitions from enrollment to incident stroke/dementia, progression to stroke-dementia comorbidity, and ultimately to mortality.

Methods: This prospective study was conducted based on the UK Biobank cohort. Frailty was assessed using the frailty index (FI) and categorized as robust (FI ≤ 0.10), prefrail (0.10 < FI ≤ 0.25), or frail (FI > 0.25). We used multi-state models and one-sample Mendelian randomization (MR) to investigate the relationships between frailty and the progression trajectories of stroke-dementia comorbidity. Population attributable fraction (PAF) analyses were conducted to assess the attributable risks of frailty and its components.

Results: The final analysis included 459,924 participants. In comparison to the robust, the frail group significantly elevated the risk of transitioning from enrollment to stroke [HR(95 %CI): 2.32(2.19-2.45)], from enrollment to dementia [2.56(2.31-2.83)], from enrollment to mortality [2.32(2.23-2.42)], from stroke to stroke-dementia comorbidity [1.59(1.23-2.05)], from dementia to stroke-dementia comorbidity [1.79(1.29-2.48)], and from stroke to mortality [1.25(1.11-1.40)]. MR analyses revealed that genetically predicted FI was causally associated with higher risks of stroke-dementia comorbidity. PAF analyses indicated that hypertension, diabetes, lung disease, and visual impairment were significant contributors to the risk of progression to stroke-dementia comorbidity.

Conclusion: Our findings revealed that frailty status increases the risk of post-stroke dementia, offering important insights for the clinical management and public health strategies.