Damage to white matter networks resulting from small vessel disease and the effects on cognitive function

White matter hyperintensities (WMHs) are prevalent in older age and are associated with cognitive decline. The location and extent of WMHs likely influences the relationship with behavior. Identifying which tracts are more likely impacted by WMHs might enable better understanding of which behaviors are affected. Therefore, this study aimed to i) identify which white matter tracts are most affected by WMHs, and ii) identify tracts where the presence of WMHs is associated with poorer cognitive scores. Participants (N = 212, 20-80 years) completed the Montreal Cognitive Assessment (MoCA). WMHs were manually delineated on FLAIR scans. In DSIStudio, we used the Human Connectome Project 1065FIB template to track how many fibers of each white matter tract intersected each participant's WMH map. Values obtained represent disconnection associated with WMHs. These scores were correlated with age, MoCA total and memory index scores. There was significantly more disconnection with older age in the right arcuate fasciculus, extreme capsule, frontal aslant tract, bilateral inferior, middle and superior longitudinal fasciculi, and the corpus callosum. Disconnection associated with WMHs in the right superior longitudinal fasciculus was significantly associated with a lower MoCA scores. Finally, disconnection in the right extreme capsule, middle and superior longitudinal fascicli, and bilateral frontal aslant tracts were significantly associated with lower MoCA memory index scores. This study highlights the prevalence of WMHs across the lifespan and demonstrates a clear relationship between tract-specific WMHs and cognition. Age-related white-matter degeneration was pronounced in many association fibers, particularly in the right hemisphere. These data suggest age related disruption of specific white matter tracts represents a clear and present risk factor for global cognition and memory as we age.

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Journal
Scientific Reports
Published
2025-07-30
DOI
https://doi.org/10.1038/s41598-025-13813-7
Primary Topic
Neurological Disease Mechanisms and Treatments
Type
article
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article

Damage to white matter networks resulting from small vessel disease and the effects on cognitive function

Julius Fridriksson, Alex Teghipco, Natalie Busby, Sarah Newman‐Norlund et al.
Scientific Reports
Neurological Disease Mechanisms and Treatments
article

Damage to white matter networks resulting from small vessel disease and the effects on cognitive function

Julius Fridriksson, Alex Teghipco, Natalie Busby, Sarah Newman‐Norlund, Sara Sayers, Leonardo Bonilha, Sarah Wilson, Chris Rorden, Janina Wilmskoetter, Nicholas Riccardi, Rebecca Roth, Lumi Bakos, Roger Newman-Norlund
article en

Abstract

White matter hyperintensities (WMHs) are prevalent in older age and are associated with cognitive decline. The location and extent of WMHs likely influences the relationship with behavior. Identifying which tracts are more likely impacted by WMHs might enable better understanding of which behaviors are affected. Therefore, this study aimed to i) identify which white matter tracts are most affected by WMHs, and ii) identify tracts where the presence of WMHs is associated with poorer cognitive scores. Participants (N = 212, 20-80 years) completed the Montreal Cognitive Assessment (MoCA). WMHs were manually delineated on FLAIR scans. In DSIStudio, we used the Human Connectome Project 1065FIB template to track how many fibers of each white matter tract intersected each participant's WMH map. Values obtained represent disconnection associated with WMHs. These scores were correlated with age, MoCA total and memory index scores. There was significantly more disconnection with older age in the right arcuate fasciculus, extreme capsule, frontal aslant tract, bilateral inferior, middle and superior longitudinal fasciculi, and the corpus callosum. Disconnection associated with WMHs in the right superior longitudinal fasciculus was significantly associated with a lower MoCA scores. Finally, disconnection in the right extreme capsule, middle and superior longitudinal fascicli, and bilateral frontal aslant tracts were significantly associated with lower MoCA memory index scores. This study highlights the prevalence of WMHs across the lifespan and demonstrates a clear relationship between tract-specific WMHs and cognition. Age-related white-matter degeneration was pronounced in many association fibers, particularly in the right hemisphere. These data suggest age related disruption of specific white matter tracts represents a clear and present risk factor for global cognition and memory as we age.

Scientific ReportsVol. 15(1)
Emory University (US), Medical University of South Carolina (US), University of South Carolina (US)
Openalex Percentile: Top 76%
Neurological Disease Mechanisms and Treatments
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