LAUSR

BACKGROUND To compare risk factors, neuroimaging characteristics, and prognosis between two clinical prodromes of dementia, namely: the motoric cognitive risk syndrome (MCRS) and mild cognitive impairment (MCI). METHODS Between 2009 and 2015, dementia-free participants of the population-based Rotterdam Study were classified with a dementia prodrome if they had subjective cognitive complaints and scored >1 standard deviations (SD) below the population mean of gait speed (MCRS) or >1.5 SD below the population mean of cognitive test scores (MCI). Using multinomial logistic regression models, we determined cross-sectional associations of risk factors and structural neuroimaging markers with MCRS and MCI, followed by subdistribution hazard models, to determine risk of incident dementia until 2016. RESULTS Of 3,025 included participants (mean age 70.4 years, 54.7% women), 231 had MCRS (7.6%), 132 had MCI (4.4%), and 62 (2.0%) fulfilled criteria for both. Although many risk factors were shared, a higher body mass index predisposed to MCRS, whereas male sex and hypercholesterolemia were associated with MCI only. Grey matter volumes, hippocampal volumes, white matter hyperintensities and structural white matter integrity were worse in both MCRS and MCI. During a mean follow-up of 3.9 years, 71 individuals developed dementia and 200 died. Five-year cumulative risk of dementia was 7.0% [2.5-11.5%] for individuals with MCRS, versus 13.3% [5.8-20.8%] with MCI and only 2.3% [1.5-3.1%] in unaffected individuals. CONCLUSIONS MCRS is associated with imaging markers of neurodegeneration and risk of dementia, even in the absence of MCI, highlighting the potential of motor function assessment in early risk stratification for dementia.