Elevated blood homocysteine increases the risk of incident Motoric Cognitive Risk syndrome: A two cohort study

Abstract Background Motoric Cognitive Risk (MCR) syndrome, a pre-dementia syndrome characterized by cognitive complaints and slow gait, may have an underlying vascular etiology. Elevated blood levels of homocysteine, a known vascular risk factor, have been linked to physical and cognitive decline in older adults, though the relationship with MCR is unknown. We aimed to identify the association between homocysteine and MCR risk. Methods We examined the association between baseline homocysteine levels and incident MCR using Cox proportional hazard models in 1,826 community-dwelling older adults (55% female) from two cohorts (Einstein Aging Study [EAS] and Quebec Longitudinal Study on Nutrition and Successful Aging [NuAge]). We calculated hazard ratios (HR) with 95% confidence intervals (CI), for each cohort as well as stratified by sex and vascular disease/risk factors. Results Median follow-up time was 2.2 years in EAS and 3.0 years in NuAge. Individuals with elevated baseline homocysteine levels (> 14 µmol/L) had a significantly higher risk of incident MCR compared to those with normal levels in NuAge (HR 1.41, 95% CI = 1.01-1.97, p = .04), after adjusting for covariates. Our exploratory stratified analyses found that these associations were significant only in men with vascular disease/risk factors. Conclusions Higher blood homocysteine levels are associated with increased risk of developing MCR in older adults, particularly in men with vascular disease or vascular risk factors.