Aetiology and prognosis of the motoric cognitive risk syndrome: A population‐based comparison with mild cognitive impairment

Abstract

AbstractBackgroundThe motoric cognitive risk syndrome (MCRS) has been proposed as a dementia prodrome that improves clinical risk stratification, by integrating slow gait and cognitive complaints. It remains undetermined to what extent pathophysiological substrates in terms of clinical risk factors, neuroimaging correlates and associations of MCRS with dementia are independent of the widely used concept of mild cognitive impairment (MCI).MethodsBetween 2009 and 2015, subjective cognitive complaints, objective cognitive impairment and gait speed were assessed in 3,025 dementia‐free participants of the population‐based Rotterdam Study (mean age 70.4 years, 54.7% women). In line with prior studies, MCI and MCRS were defined as subjective complaints along with a score of >1.5 and >1 standard deviations below the population mean of the neuropsychological test battery and gait speed, respectively. We used multinomial logistic regression models to determine cross‐sectional associations of clinical risk factors and neuroimaging markers with MCI and MCRS, and subsequently assessed risk of dementia or death, with follow‐up until 2016, in a competing risk framework.ResultsOf 3,025 individuals, 231 had MCRS (7.6%), 132 had MCI (4.4%), and 62 (2.0%) fulfilled criteria for both. Smoking, hypertension, diabetes and APOE‐ε4 carriership were shared risk factors between MCRS and MCI, but higher BMI predisposed predominantly to MCRS, whereas male sex and hypercholesterolemia were associated with MCI only. Lower total brain volume was more strongly related to MCI than to MCRS, driven by a difference in white matter volume. During a mean follow‐up of 3.9 years, 71 individuals developed dementia and 200 died. Compared to unaffected individuals, risk of dementia was higher with MCI and to a lesser extent with MRCS (subdistribution hazard ratio [95% confidence interval]: 6.95 [3.78‐12.75] and 3.55 [1.91‐6.60], respectively). Accounting for a higher mortality risk, 5‐year risk of dementia was 7.0% [2.5‐11.5%] for individuals with MCRS, versus 13.3% [5.8‐20.8%] with MCI and 2.3% [1.5‐3.1%] in unaffected individuals.ConclusionIn people with subjective cognitive complaints, both cognitive and motor function impairment are associated with dementia risk, with in part different pathophysiological substrates. While MCI has greater utility for dementia prediction, incorporation of motor function in clinical assessments may increase prognostic accuracy.