Thalamic volume alterations mediate glymphatic function and cognitive dysfunction in Alzheimer's disease
Leian Chen, Xiao Zhou, Bin Zhang, Ying Hou, Yu Sun, Dantao Peng,Abstract
INTRODUCTION
Glymphatic dysfunction is implicated in Alzheimer's disease (AD), but its mechanism remains unclear. This study investigated the associations of the analysis along the perivascular space (ALPS) index, brain reserve, and cognitive outcomes across the AD continuum.
METHODS
This study enrolled two cohorts from the local hospital ( n = 95) and the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 178). We calculated the diffusion tensor image ALPS to assess the whole‐brain glymphatic function and evaluated its associations with cognition and brain structure.
RESULTS
A higher ALPS index was positively associated with better executive, memory, and language abilities ( p < 0.05). A lower ALPS index correlated with thalamic atrophy, involving the anterior, lateral, ventral, and midline thalamic nuclei. Thalamic atrophy mediated the link between glymphatic dysfunction and worse cognition via structural association of full or part mediation.
CONCLUSIONS
Glymphatic system deterioration correlates with cognitive decline, potentially mediated by thalamic atrophy. The thalamic nuclei may be critical in this pathway.