Independent Role of White Matter Hyperintensity Volume and Location in Alzheimer's Disease Risk Beyond Hippocampal
Hyun Ju Yang1, Jae Min Song2, Joon Hyuk Park1,3
1Department of Psychiatry, Jeju National University School of Medicine, Jeju National University Hospital, Jeju Special Self-Governing Province, Republic of Korea.
Objective:
Increases in white matter hyperintensities (WMH) observed on brain MRI are associated with the onset of Alzheimer's disease (AD) and cognitive decline. Recent hypotheses suggest that the impact of WMH on cognition may differ by their distance from the ventricular surface. This study aimed to investigate the effects of WMH volume and location, classified by distance from the ventricular surface, on cognitive function in individuals with AD.
Methods:
A total of 112 normal cognition (NC) individuals and 171 patients with AD underwent clinical evaluation, volumetric MRI, and neuropsychological testing using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease. WMH volume was categorized as juxtaventricular (JVWMH, <3 mm from ventricle), periventricular (PVWMH, 3-13 mm), and deep (DWMH, >13 mm).
Results:
The mean WMH volume was significantly higher in AD group (20.7±18.2 mL) than in the NC group (6.8±8.1 mL, p<0.001). A tenfold increase in WMH volume led to a 5.967-fold increased risk of AD (95% confidence interval [CI]=1.550-22.986). A similar risk association was observed for PVWMH (OR=4.021, 95% CI=1.592-10.156), and DWMH showed a significant risk association (OR= 2.873, 95% CI=1.227-6.731). Total WMH, JVWMH, and PVWMH were associated with poorer performance in verbal fluency and memory tasks, while DWMH showed no significant cognitive association.
Conclusion:
WMH volume and location independently contribute to AD risk and cognitive decline, with PVWMH and JVWMH particularly affecting executive and memory functions, regardless of hippocampal atrophy.
Insights
White matter hyperintensities (WMH) increase Alzheimer's disease (AD) risk and cognitive decline. Their location matters, with juxtaventricular and periventricular WMH significantly impacting memory and executive functions.
Area of Science:
- Neuroimaging and Neurology
- Cognitive Neuroscience
Background:
- White matter hyperintensities (WMH) on MRI are linked to Alzheimer's disease (AD) and cognitive decline.
- WMH impact on cognition may vary based on proximity to the ventricular surface.
Purpose of the Study:
- To investigate how WMH volume and location, specifically distance from the ventricles, affect cognitive function in AD patients.
- To differentiate the cognitive impact of juxtaventricular, periventricular, and deep WMH.
Main Methods:
- Volumetric MRI and neuropsychological testing were performed on 112 normal cognition (NC) individuals and 171 AD patients.
- WMH were categorized by distance: juxtaventricular (JVWMH, <3 mm), periventricular (PVWMH, 3-13 mm), and deep (DWMH, >13 mm).
Main Results:
- AD patients had significantly higher mean WMH volume than NC individuals (20.7 vs. 6.8 mL).
- Increased WMH volume correlated with higher AD risk. PVWMH and DWMH showed significant risk associations.
- JVWMH and PVWMH were associated with poorer verbal fluency and memory, while DWMH showed no significant cognitive association.
Conclusions:
- WMH volume and location are independent contributors to AD risk and cognitive decline.
- Periventricular and juxtaventricular WMH particularly impair executive and memory functions, irrespective of hippocampal atrophy.
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