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Cognitive Reserve Disrupts Cognitive Decline from White Matter Hyperintensities
Arthur P Hamilton1, Kaiah N Sotebeer2, John G Grundy2
1Carleton University, Department of Cognitive Science.
Medrxiv : the Preprint Server for Health Sciences
|September 2, 2025
Summary
White matter hyperintensities (WMHs) disrupt brain connectivity, impacting cognitive performance in older adults. Cognitive reserve may offset these negative effects, preserving cognition despite WMH-induced network disruption.
Area of Science:
- Neuroscience
- Gerontology
- Medical Imaging
Background:
- Previous studies on white matter hyperintensities (WMHs) and cognitive decline primarily assessed overall lesion burden.
- A novel Lesion Quantification Toolkit (LQT) enables measurement of localized connectivity disruption caused by WMHs.
Purpose of the Study:
- To apply the LQT to assess the impact of WMH-induced localized connectivity disruption on cognitive function in healthy aging.
- To investigate the relationship between WMH-related network disruption, cognitive impairment, and cognitive reserve.
Main Methods:
- Utilized three existing MRI datasets from older adults (N=259).
- Employed the Lesion Quantification Toolkit (LQT) to quantify localized disruptions in brain connectivity due to WMHs.
- Applied partial least-squares path modeling to analyze relationships between connectivity disruption, cognitive performance, age, and cognitive reserve.
Main Results:
- Confirmed a significant association between connectivity disruption and reduced cognitive performance.
- In a dataset with detailed cognitive reserve measures, higher cognitive reserve was linked to better cognitive performance.
- Findings suggest cognitive reserve can mitigate the adverse cognitive effects of WMHs.
Conclusions:
- Localized connectivity disruption by WMHs is a key factor in cognitive decline among older adults.
- Cognitive reserve plays a crucial role in maintaining cognitive function by potentially buffering the impact of WMH-related brain changes.
- The LQT offers a more refined approach to understanding the neurobiological underpinnings of cognitive aging.
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