Cholinergic subcortical hyperintensities in Alzheimer's disease patients from the Sunnybrook Dementia Study:
Alicia A McNeely1, Joel Ramirez1, Sean M Nestor2
1LC Campbell Cognitive Neurology Research Unit, Sunnybrook Heath Sciences Centre, Toronto, Canada Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre, Toronto, Canada Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Canada.
Background:
Subcortical hyperintensities within the cholinergic fiber projections (chSH) on MRI are believed to reflect cerebral small vessel disease (SVD) which may adversely impact cognition. Additionally, hippocampal atrophy represents a commonly used biomarker to support the diagnosis of Alzheimer's disease (AD).
Objective:
To examine potential differences in neuropsychological test performance between AD patients (n = 234) with high and low chSH volumes and whether these differences corresponded to hippocampal atrophy.
Methods:
A modified version of Lesion Explorer was used to volumetrically quantify chSH severity. The Sunnybrook Hippocampal Volumetry Tool was applied to obtain hippocampal volumes. Composite z-scores to assess executive, memory, and visuospatial functioning were generated from standardized neuropsychological test performance scores.
Results:
Inter-method technique validation demonstrated a high degree of correspondence with the Cholinergic Pathways Hyperintensities Scale (n = 40, ρ = 0.84, p < 0.001). After adjusting for brain atrophy, disease severity, global SH volumes, and demographic variables, multivariate analyses revealed a significant group difference, with the high chSH group demonstrating poorer memory function compared to the low chSH group (p = 0.03). A significant difference was found between low and high chSH groups in total (p < 0.05) and left (p < 0.01) hippocampal volume.
Conclusion:
These results suggest degradation of the cholinergic projections due to strategic SVD may independently contribute to memory dysfunction and hippocampal atrophy. Future studies examining subcortical vasculopathy in the cholinergic pathways may have implications on the development of therapeutic strategies for dementia and SVD.
Insights
Subcortical hyperintensities in cholinergic pathways (chSH) are linked to poorer memory function and hippocampal atrophy in Alzheimer's disease (AD) patients. This suggests small vessel disease (SVD) in these pathways may independently impact cognition.
Area of Science:
- Neuroimaging
- Neurology
- Cognitive Science
Background:
- Subcortical hyperintensities in cholinergic fiber projections (chSH) are associated with cerebral small vessel disease (SVD) and may impair cognition.
- Hippocampal atrophy is a key biomarker for Alzheimer's disease (AD) diagnosis.
Purpose of the Study:
- To investigate differences in neuropsychological performance between AD patients with high and low chSH volumes.
- To determine if these performance differences correlate with hippocampal atrophy.
Main Methods:
- Volumetric quantification of chSH severity using a modified Lesion Explorer.
- Assessment of hippocampal volumes using the Sunnybrook Hippocampal Volumetry Tool.
- Generation of composite z-scores for executive, memory, and visuospatial functions.
Main Results:
- High chSH volume was associated with poorer memory function compared to low chSH volume, even after adjusting for confounding factors.
- Significant differences in total and left hippocampal volumes were observed between high and low chSH groups.
- High correspondence was found between the volumetric quantification method and the Cholinergic Pathways Hyperintensities Scale.
Conclusions:
- Degradation of cholinergic projections due to SVD may independently contribute to memory decline and hippocampal atrophy.
- Findings highlight the potential role of subcortical vasculopathy in the cholinergic pathways in dementia.
- Further research into cholinergic pathway vasculopathy could inform therapeutic strategies for dementia and SVD.
