Thalamic volume alterations mediate glymphatic function and cognitive dysfunction in Alzheimer's disease
Leian Chen1, Xiao Zhou2, Bin Zhang3
1Epilepsy Center Department of Neurology Second Affiliated Hospital School of Medicine, Zhejiang University Hangzhou China.
Alzheimer'S & Dementia (New York, N. Y.)
|August 7, 2026
Summary
Glymphatic system dysfunction, measured by the ALPS index, is linked to cognitive decline in Alzheimer's disease. Thalamic atrophy may mediate this relationship, highlighting its role in neurodegeneration.
Area of Science:
- Neuroscience
- Radiology
- Gerontology
Background:
- Glymphatic system dysfunction is associated with Alzheimer's disease (AD).
- The precise mechanisms linking glymphatic function to AD pathology and cognitive decline are not fully understood.
- This study explores the relationship between glymphatic function, brain reserve, and cognitive outcomes in the AD continuum.
Purpose of the Study:
- To investigate the association between the Analysis along the Perivascular Space (ALPS) index, a measure of glymphatic function, and cognitive performance.
- To examine the relationship between the ALPS index and brain structure, specifically thalamic atrophy.
- To determine if thalamic atrophy mediates the link between glymphatic dysfunction and cognitive decline.
Main Methods:
- Two cohorts were analyzed: a local hospital cohort (n=95) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (n=178).
- Diffusion tensor imaging was used to calculate the ALPS index, assessing whole-brain glymphatic function.
- Statistical analyses evaluated associations between the ALPS index, cognitive function (executive, memory, language), and brain structure (thalamic nuclei).
Main Results:
- A higher ALPS index was significantly associated with better executive, memory, and language abilities (p < 0.05).
- A lower ALPS index correlated with atrophy in multiple thalamic nuclei, including anterior, lateral, ventral, and midline regions.
- Thalamic atrophy was found to mediate the relationship between impaired glymphatic function and poorer cognitive outcomes.
Conclusions:
- Deterioration of the glymphatic system, indicated by a lower ALPS index, is correlated with cognitive decline in individuals across the AD spectrum.
- Thalamic atrophy appears to be a key mediator in the pathway linking glymphatic dysfunction to cognitive impairment.
- Specific thalamic nuclei may play a critical role in the neurodegenerative processes associated with Alzheimer's disease.
Keywords:
Alzheimer's diseasecognitive functiondiffusion tensor image analysis along the perivascular spaceglymphatic systemthalamusMore Related Videos
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