Associations between amyloid-β load and cognition in cerebrovascular disease beyond cerebral amyloid angiopathy: a systematic review and meta-analysis of positron emission tomography studies.

Background There is growing interest in the comorbidity of vascular and neurodegenerative pathologies in patients with cerebrovascular disease (CVD) beyond cerebral amyloid angiopathy (CAA). However, the relationship between amyloid-β and vascular cognitive impairment (VCI) remains debated. Objective To investigate the association between VCI and amyloid-β deposition in non-CAA CVD patients. Methods PubMed, Embase, Web of Science, PsycINFO and CENTRAL databases were systematically searched. Observational studies, including case–control and cohort studies, associating cognitive scores with amyloid load measured by positron emission tomography were selected. Meta-analyses were performed to assess the strength of amyloid–cognition associations across CVD subtypes and cognitive domains. A random-effects model using the inverse variance method was used, with heterogeneity evaluated by Q-statistics and I2 statistics. Meta-regression analyses were conducted to examine the influence of moderators, and publication bias was assessed using funnel plots and Egger's test. All statistical analyses were performed using StataMP 18. Results Twenty-seven eligible studies encompassing 2894 participants were included. Among non-CAA CVD patients, global cognitive performance was significantly lower in those with higher amyloid-β deposition (standardized mean difference = −0.43, P < 0.001). The correlation strength varied across cognitive domains (executive function: r = −0.41; language: r = −0.36; memory: r = −0.29; all P < 0.001). The correlation was significant in patients with subcortical vascular disease (r = −0.43, P < 0.001) but not post-stroke patients (r = −0.19, P > 0.05). Conclusions Amyloid-β load is associated with cognitive decline in non-CAA CVD patients. This is more pronounced in patients with subcortical vascular disease than in post-stroke patients. Executive function is the most susceptible domain in VCI when the level of amyloid-β increases. [ABSTRACT FROM AUTHOR]