Risk factors for the progression of motoric cognitive risk syndrome to dementia: Retrospective cohort analysis of two populations

Background and purpose: Motoric cognitive risk syndrome (MCR) is a predementia syndrome characterized by cognitive complaints and slow gait. MCR is associated with increased risk of cognitive decline and incident dementia. Predictors of transition to dementia in MCR patients are still obscure. Methods: We examined clinical, biological and lifestyle parameters related to conversion to dementia using Cox models in 439 older adults with prevalent MCR (mean age 79.87 ± 8.13 years, 70% women) from two cohorts, 268 from the Chicago-based Rush Memory and Aging project (MAP) and 171 from the Religious Orders Study (ROS), which enrolled religious clergy across the United States. Results: In the pooled sample, 439 (13.2%) had prevalent MCR (268 MAP and 171 ROS). There were 140 (31.9%) incident dementia cases over a median follow up of 4.0 years. Age predicted conversion from MCR to dementia in both cohorts. Male gender was a risk factor only in ROS. In the pooled data, only higher depressive symptoms were associated with higher risk of conversion to dementia (adjusted hazard ratio [aHR] 1.13, 95% CI 1.03–1.24). Lower cognitive activity participation (aHR 0.59, 95% CI 0.44–0.79) and apolipoprotein E ε4 allele (aHR 2.57, 95% CI 1.48–4.45) predicted conversion to dementia in MAP. Conclusions: Depressive symptoms and other cohort-specific risk factors were identified as predictors of transition to dementia in individuals with MCR. These findings suggest common pathological mechanisms underlying mood, gait and cognitive declines in aging, which could help develop preventive strategies.