Motoric cognitive risk syndrome, incident cognitive impairment and morphological brain abnormalities: Systematic review and meta-analysis

Background: Motoric cognitive risk syndrome (MCR) is a pre-dementia stage, which associates slow walking speed with subjective cognitive impairment (SCI). MCR's clinical utility for the prediction of dementia and its pathophysiology are unclear. The aim of this systematic review and meta-analysis is to examine the association of MCR with incident cognitive impairment, cognitive performance and brain structures. Methods: A systematic search was conducted using the Medical Subject Heading terms "Walking" and "Cognition disorders" combined with the terms "Subjective cognitive impairment", "Subjective cognitive decline" and "Motoric cognitive risk". A total of 11 studies were included in the systematic review and meta-analysis: 3 studies had dementia as the outcome, 3 studies had cognitive performance as the outcome, 4 studies had brain structures as the outcome and one study examined the incidence of both major neurocognitive disorders and cognitive impairment. Results: MCR was found to be associated with incident cognitive impairment (pooled hazard ratio (HR) = 1.70, 95% CI, 1.46-1.98 with P-value < 0.001) and dementia (pooled HR = 2.50, 95% CI, 1.75-2.39 with P-value < 0.001). MCR was also found to be associated with low grey matter volume involving the premotor and the prefrontal cortex, and lacunar lesions in the frontal lobe. No significant association was found with white matter abnormalities. Conclusion: MCR predicts cognitive impairment and dementia, suggesting that it may be used as a screening syndrome for dementia in a primary care setting. Its significant association with both low grey matter volume and lacunar lesions makes its pathophysiology unclear and suggests multiple pathways.