Motoric cognitive risk syndrome: Integration of two early harbingers of dementia in older adults

Abstract

Dementia is characterized by a long preclinical phase that may last years to decades before the onset of mild cognitive impairment. Slow gait speed and subjective memory complaint commonly co-occur during this preclinical phase, and each is a strong independent predictor of cognitive decline and dementia. Motoric cognitive risk (MCR) syndrome is a pre-dementia syndrome that combines these two early harbingers of dementia. The risk of cognitive decline or dementia is stronger for MCR than for either slow gait speed or subjective memory complaint alone. Slow gait speed and subjective memory complaint have several common risk factors: cardiovascular disease, diabetes mellitus, abnormal cortisol profiles, low vitamin D levels, brain atrophy with decreased hippocampal volume, and increased deposition of beta-amyloid in the brain. The underlying pathogenesis of MCR remains poorly understood. Metabolomics and proteomics have great potential to provide new insights into biological pathways involved in MCR during the long preclinical phase preceding dementia.

Keywords: Alzheimer’s disease; Cognitive decline; Dementia; Gait; Memory; Skeletal muscle.

Fig. 1.

Hypothetical model of the trajectory of cognitive performance in relation to progression to Alzheimer’s disease (AD). Subjective memory complaint and slow gait speed can occur during the long preclinical phase and increase the risk of progression to MCI and AD. This is a hypothetical model and does not imply that all individuals with decline of cognitive performance will progress to dementia.

Fig. 2.

Conceptual model of MCR showing known and probable risk factors. Broken arrows signify other modulating factors.