Epidemiology and Outcomes Associated with Cognitive Frailty and Reserve in a Stroke Population: Systematic Review and Meta-Analysis.

Introduction: Cognitive frailty and the related concepts of cognitive reserve and imaging-based brain frailty are of increasing interest in older adult care. However, there is uncertainty regarding their importance within a stroke population. We aimed to establish the prevalence of cognitive frailty and reserve in stroke and determine impact on outcomes.

Methods: We conducted a systematic review across multidisciplinary electronic databases using validated search syntax. The protocol for this review has been published (PROSPERO, CRD42023433385). We identified studies on cognitive frailty and cognitive reserve, including studies that used related concepts. We extracted data to inform estimates of prevalence and associations with outcomes of physical function, cognition and quality of life, performing meta-analyses where possible. Risk of bias was assessed using Newcastle-Ottawa tools appropriate to study design.

Results: Our search returned 12,095 studies, from which 14 papers met our criteria. No studies described cognitive frailty, and rather studies described cognitive reserve and brain frailty. Cognitive reserve was assessed using proxy measures of education, employment, and leisure time. Four studies used the Cognitive Reserve Index Questionnaire (CRIq) with pooled estimate score of 103.25, 95% CI: 96.87-109.65 (indicating moderate cognitive reserve). Cognitive reserve had varying associations with post-stroke outcomes, three studies (n = 7,759 participants) reporting significant negative association with cognitive measures. Brain frailty was assessed using imaging markers. Across four studies (n = 3,086 participants), pooled prevalence of brain frailty was 73.8%, 95% CI: 72.2-75.3. Higher brain frailty was associated with poorer post-stroke outcomes for majority of studies assessed. Seven studies (50%) were scored as low risk of bias.

Conclusion: Attempts to synthesise these data were complicated by inconsistency in terminology and heterogeneity in methods. However, our findings suggest that brain frailty is common in stroke and associated with poorer outcomes. The epidemiology of cognitive frailty and reserve is less well described. All these measures may be useful for prognostication in stroke, but there are multiple areas where more research is needed.