Is carotid artery atherosclerosis associated with poor cognitive function assessed using the Mini-Mental State Examination? A systematic review and meta-analysis

OBJECTIVES: To determine associations between carotid atherosclerosis assessed by ultrasound and the Mini-Mental State Examination (MMSE), a measure of global cognitive function. DESIGN: Systematic review and meta-analysis. METHODS: MEDLINE and EMBASE databases were searched up to 1 May 2020 to identify studies assessed the associations between asymptomatic carotid atherosclerosis and the MMSE. Studies reporting OR for associations between carotid plaque or intima-media thickness (cIMT) and dichotomised MMSE were meta-analysed. Publication bias of included studies was assessed. RESULTS: A total of 31 of 378 reviewed articles met the inclusion criteria; together they included 27 738 participants (age 35–95 years). Fifteen studies reported some evidence of a positive association between measures of atherosclerosis and poorer cognitive performance in either cross-sectional or longitudinal studies. The remaining 16 studies found no evidence of an association. Seven cross-sectional studies provided data suitable for meta-analysis. Meta-analysis of three studies that assessed carotid plaque (n=3549) showed an association between the presence of plaque and impaired MMSE with pooled estimate for the OR (95% CI) being 2.72 (0.85 to 4.59). An association between cIMT and impaired MMSE was reported in six studies (n=4443) with a pooled estimate for the OR (95% CI) being 1.13 (1.04 to 1.22). Heterogeneity across studies was moderate to small (carotid plaque with MMSE, I(2)=40.9%; cIMT with MMSE, I(2)=4.9%). There was evidence of publication bias for carotid plaque studies (p=0.02), but not cIMT studies (p=0.2). CONCLUSIONS: There is some, limited cross-sectional evidence indicating an association between cIMT and poorer global cognitive function assessed with MMSE. Estimates of the association between plaques and poor cognition are too imprecise to draw firm conclusions and evidence from studies of longitudinal associations between carotid atherosclerosis and MMSE is limited. PROSPERO REGISTRATION NUMBER: CRD42021240077.