Risk factors, neuroimaging correlates and prognosis of the motoric cognitive risk syndrome: A population‐based comparison with mild cognitive impairment

Abstract

Background and purpose This study was undertaken 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 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 3025 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. Gray 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.

Prevalence and predictors of Motoric Cognitive Risk syndrome in a community‐dwelling older Scottish population: A longitudinal observational study

“…A recent study comparing MCR and MCI found many shared risk factors but also noted that differences in gender, hypercholesterolaemia, BMI, and cerebral white matter volumes indicate different pathophysiological substrates 38 . This study also reported that MCR captured early features of dementia in the absence of MCI 38 …”

“…37 A recent study comparing MCR and MCI found many shared risk factors but also noted that differences in gender, hypercholesterolaemia, BMI, and cerebral white matter volumes indicate different pathophysiological substrates. 38 This study also reported that MCR captured early features of dementia in the absence of MCI. 38 This is the first study to explore the overlap of MCR and Frailty according to Fried phenotype (characterised as the presence of five components: weakness, slowness, exhaustion, low physical activity, and unintentional weight loss).…”

“…38 This study also reported that MCR captured early features of dementia in the absence of MCI. 38 This is the first study to explore the overlap of MCR and Frailty according to Fried phenotype (characterised as the presence of five components: weakness, slowness, exhaustion, low physical activity, and unintentional weight loss). 39 Given the degree of overlap found, it is surprising that individual characteristics of Frailty, such as grip strength and BMI were not significantly different between the MCR and non-MCR groups at all waves.…”

“…This may be partly because gait speed slows as early as 10 years before the diagnosis of MCI and some literature suggests that slow gait may precede declines in cognitive function tests 37 . A recent study comparing MCR and MCI found many shared risk factors but also noted that differences in gender, hypercholesterolaemia, BMI, and cerebral white matter volumes indicate different pathophysiological substrates 38 . This study also reported that MCR captured early features of dementia in the absence of MCI 38 …”

Associations between blood-based biomarkers of Alzheimer’s disease with cognition in motoric cognitive risk syndrome: A pilot study using plasma Aβ42 and total tau

“…Previous studies revealed that MCR could be related to cortical atrophy ( Blumen et al, 2021 ), lacunar infarction ( Wang et al, 2016 ), or increased levels of systematic inflammatory biomarkers ( Bortone et al, 2021 ). A cross-sectional study using MRI found that gray matter volumes, hippocampal volumes, and white matter hyperintensities were worse in individuals with MCR ( Yaqub et al, 2022 ). Meiner et al (2021) also reported that Apolipoprotein E ε4 allele (APOE ε4) was associated with the conversion to dementia in older adults with MCR.…”