Smaller cingulate grey matter mediates the association between dual-task gait and incident dementia

Individuals with mild cognitive impairment who have high dual-task gait cost (≥20% slowing in gait speed while performing a cognitive brain-demanding task) are 3-fold more likely to progress to dementia. However, the cortical regions that might explain this association are unknown, which might identify potentially treatable areas. The aim of the present study was to investigate whether brain grey matter volume loss and motor cortex metabolite levels explain the association between dual-task cost and incident dementia in individuals with mild cognitive impairment. We included participants with mild cognitive impairment from the Gait and Brain Study Cohort, who had a baseline MRI and were followed up for 9 years with cognitive and gait assessments every 6 months. Gait performance was investigated in four conditions: usual gait, counting backwards by ones, naming animals and subtracting serial sevens. Dual-task cost was calculated as the percentage change in gait speed in dual-task conditions relative to usual gait speed. Data were collected from July 2007 to June 2023. From the 139 individuals with mild cognitive impairment included at baseline [mean (standard deviation) age, 73 (6) years; 62 (44%) female], 33 (24%) progressed to dementia. Baseline high dual-task cost (≥20%) during counting backwards by ones and naming animals conditions were associated with smaller grey matter volume in several brain structures. A higher ratio of choline to creatine in the primary motor cortex was associated with higher serial sevens dual-task cost. High dual-task cost while counting backwards by ones and naming animals was associated with a 3-fold risk of incident dementia (P = 0.02). Mediation analyses revealed that grey matter volume clusters localized in the right anterior and middle cingulate cortices mediated the association between counting backwards by ones dual-task cost and incident dementia (effect: 48%; P = 0.045) with no mediation observed in grey matter loss in other brain regions or through motor cortex metabolite levels. Smaller grey matter volume of the right anterior and middle cingulate cortices explained the association between high dual-task cost and incident dementia in mild cognitive impairment. This result sheds light on the neural mechanisms of cognitive-motor interaction linked with cognitive decline and dementia in mild cognitive impairment and supports the use of gait under dual-tasking as a motor biomarker of dementia.