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.