Clinical study on gray matter volume reduction, gait disorders, and fall risk in patients with Alzheimer's disease

Falls represent a major threat to the physical and mental health of older adults. This study is dedicated to determining the relationships of fall risk with reduced gray matter volume and gait disorders in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD).

24 aMCI and 21 AD patients were recruited from the Neurology Department of the Second Hospital of Hebei Medical University from January 2024 to December 2024. A prospective nested case-control design was employed on eligible participants for general data collection, neuropsychological testing, gait analysis [including single-task walking (STW) and dual-task walking (DTW)], structural MRI and following up for 6-12 months. The primary outcome was fall that occurred during the follow-up period (recorded through telephone follow-up), and the secondary outcomes were differences in baseline cognitive function, gait parameters, and brain structure between the fall group and the non-fall group. Subjects were categorized as fallers or non-fallers based on incident falls during follow-up. Univariate analysis was performed to screen for potential risk factors contributing to falls. Logistic regression analysis was employed to identify the independent risk factors for falls in aMCI and AD. Furthermore, disparities in gray matter volume between the fall and non-fall groups were investigated by voxel-based morphometry (VBM) analysis (the false discovery rate (FDR) correction based on clumps was adopted, p < 0.05).

In this preliminary queue with limited sample size, body mass index (BMI), stride length variability, and medication burden were found to be independent predictors of incident falls by univariate and multivariate analyses. The results of VBM suggested significantly reduced gray matter volume in fallers within the left cerebellar Crus I, lobule VI, and fusiform gyrus; right cerebellar lobule VI, fusiform gyrus, and lobule IV-V; and right superior and middle temporal gyrus, compared with non-fallers.

The preliminary findings of this study indicate that BMI, stride length variability, and medication burden may be associated with fall risk and reduced gray matter volume in specific brain region may be a potential neuroanatomical basis for increased risk of falls in AD patients, which need to be further validated in larger cohorts.