Neuroimaging Biomarkers in Motoric Cognitive Risk Syndrome: A Systematic Review of Structural, Functional, and Molecular Correlates

Background: Motoric cognitive risk (MCR) syndrome is an operationally defined predementia syndrome characterized by slow gait and cognitive complaints. We aimed to systematically synthesize evidence from neuroimaging modalities, including structural, functional, and molecular imaging, to elucidate the biological mechanisms underlying MCR. Methods: We searched PubMed, Embase, CINAHL, and Web of Science from inception to March 2025, with an update in June 2026. Studies reporting neuroimaging measures in individuals with MCR compared to those without were included. Data were extracted independently by two reviewers. Methodological quality was assessed using the Joanna Briggs Institute Checklist for Analytical Cross-Sectional Studies. A narrative synthesis was conducted following the Synthesis Without Meta-Analysis (SWiM) guidelines. Results: Twenty-one studies were included, encompassing a total screening pool of 25,515 older adults, with neuroimaging data available for 15,657. All 21 studies employed a cross-sectional design; no study reported a longitudinal neuroimaging analysis. Across ten structural MRI studies, MCR was consistently associated with smaller grey matter volumes or thinner cortex in prefrontal, premotor, insular, and parietal regions, with sex-stratified analysis showing frontal involvement in males and hippocampal involvement in females. White matter hyperintensities and cerebral small vessel disease markers were positively associated with MCR in seven studies. Three diffusion tensor imaging studies revealed widespread white matter microstructural disruption. Two positron emission tomography studies and one plasma-biomarker study consistently found no elevation of Alzheimer’s disease (AD) pathology in MCR, distinguishing it from mild cognitive impairment. Two functional near-infrared spectroscopy studies and one electroencephalography study reported prefrontal hyperactivation during dual-task walking and increased frontal theta power, suggesting compensatory neural processes. Eighteen studies (86%) were rated as low risk of bias. Conclusions: MCR is associated with a consistent neuroimaging profile characterized by frontoparietal cortical atrophy, cerebral small vessel disease, and absent AD pathology. These findings distinguish MCR from mild cognitive impairment and suggest that disruption of mobility–cognition neural networks, potentially driven by vascular brain injury, may underlie its pathogenesis. Longitudinal studies are needed to establish the temporal and causal nature of these associations. Registration: PROSPERO CRD420251011713.