To examine Alzheimer’s pathology through CSF biomarkers in memory clinic patients with and without Motoric Cognitive Risk (MCR) syndrome.

MCR, defined by subjective cognitive complaints and slow gait speed, is a clinical screening tool proposed to identify older adults at increased risk for dementia. However, the CSF biomarker profile of Alzheimer’s disease (AD) in memory clinic populations with and without MCR remains poorly characterized.

We retrospectively included 79 non-demented participants (mean age 71.4 ± 8.0 years; 38% female) from the Leenaards Memory Center (Lausanne University Hospital) and the Geneva Memory Center (Geneva University Hospital) who underwent both CSF analysis and gait assessment. CSF concentrations of amyloid-β42, phosphorylated tau, and total tau were obtained during routine lumbar puncture and A/T/N profiles were classified according to the NIA-AA research framework. Group comparisons used chi-square or Fisher’s exact tests, and multivariable logistic regression models examined associations between MCR status and CSF biomarkers, adjusting for age, sex, and education.

Thirty-nine participants (49%) met MCR criteria. MCR + and MCR - groups did not differ in age, sex, education, or global and domain-specific cognitive performance. Vascular risk factors and comorbidities were similar, although depressive symptoms were more frequent among MCR+ individuals (RR = 2.11; 95% CI 1.39 to 3.19; p < .001). A/T profiles and the proportions of biomarker-positive individuals did not differ significantly between groups. CSF biomarkers were not independently associated with MCR status in multivariable models.

In memory clinic populations, MCR is frequent among non-demented patients and CSF biomarker profiles are comparable between individuals with and without MCR. These findings suggest that MCR represents a biologically heterogenous clinical syndrome encompassing both AD and non-AD pathologies and underscore the importance of biomarker-based characterization to refine diagnostic assessment in clinical practice.