Ali Pauline, Pieruccini-Faria Frederico, Annweiler Cédric, Dinomais Mickaël, Son Surim, Wilson Scott K, Camicioli Richard, Muir-Hunter Susan, Bartha Robert, Montero-Odasso Manuel
Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, North London, Ontario, N6A 5C1, Canada.
Laboratoire Angevin de Recherche en Ingénierie des Systèmes, EA7315, University of Angers, 49000, Angers, France.
Brain. 2025 May 13;148(5):1551-1561. doi: 10.1093/brain/awae356.
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.
轻度认知障碍且双重任务步态成本高（即在执行一项对大脑认知有要求的任务时步态速度减慢≥20%）的个体发展为痴呆症的可能性高出3倍。然而，可能解释这种关联的皮质区域尚不清楚，而这可能会确定潜在的可治疗区域。本研究的目的是调查脑灰质体积减少和运动皮质代谢物水平是否能解释轻度认知障碍个体中双重任务成本与新发痴呆症之间的关联。我们纳入了步态与脑研究队列中的轻度认知障碍参与者，他们进行了基线磁共振成像（MRI）检查，并每6个月进行一次认知和步态评估，随访9年。在四种情况下对步态表现进行了研究：正常步态、逐个数数、说出动物名称和连续减7。双重任务成本计算为双重任务条件下步态速度相对于正常步态速度的百分比变化。数据收集时间为2007年7月至2023年6月。在基线时纳入的139名轻度认知障碍个体中[平均（标准差）年龄，73（6）岁；62名（44%）为女性]，33名（24%）发展为痴呆症。在逐个数数和说出动物名称的条件下，基线时较高的双重任务成本（≥20%）与多个脑结构中较小的灰质体积相关。初级运动皮质中胆碱与肌酸的比例较高与连续减7双重任务成本较高相关。在逐个数数和说出动物名称时较高的双重任务成本与新发痴呆症风险高出3倍相关（P = 0.02）。中介分析显示，位于右侧前扣带回和中扣带回皮质的灰质体积簇介导了逐个数数双重任务成本与新发痴呆症之间的关联（效应：48%；P = 0.045），在其他脑区的灰质损失或通过运动皮质代谢物水平未观察到中介作用。右侧前扣带回和中扣带回皮质较小的灰质体积解释了轻度认知障碍中高双重任务成本与新发痴呆症之间的关联。这一结果揭示了与轻度认知障碍中的认知衰退和痴呆症相关的认知 - 运动相互作用神经机制，并支持将双重任务下的步态用作痴呆症的运动生物标志物。
