The Correlation Between White Matter Hyperintensity Burden and Regional Brain Volumetry in Patients With Alzheimer's Disease

Zhiyu Cao; Yingren Mai; Wenli Fang; Ming Lei; Yishan Luo; Lei Zhao; Wang Liao; Qun Yu; Jiaxin Xu; Yuting Ruan; Songhua Xiao; Vincent C T Mok; Lin Shi; Jun Liu; Alzheimer's Disease Neuroimaging Initiative

doi:10.3389/fnhum.2022.760360

The Correlation Between White Matter Hyperintensity Burden and Regional Brain Volumetry in Patients With Alzheimer's Disease

Front Hum Neurosci. 2022 Jun 14:16:760360. doi: 10.3389/fnhum.2022.760360. eCollection 2022.

Authors

Zhiyu Cao¹, Yingren Mai¹, Wenli Fang¹, Ming Lei¹, Yishan Luo², Lei Zhao², Wang Liao^{1

3}, Qun Yu¹, Jiaxin Xu¹, Yuting Ruan¹, Songhua Xiao¹, Vincent C T Mok^{2

4}, Lin Shi^{2

5}, Jun Liu^{1

3}; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
² BrainNow Research Institute, Shenzhen, China.
³ Department of Neurology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁴ Division of Neurology, Department of Medicine and Therapeutics, Gerald Choa Neuroscience Centre, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
⁵ Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.

Abstract

Background: White matter hyperintensities (WMHs) and regional brain lobe atrophy coexist in the brain of patients with Alzheimer's disease (AD), but the association between them in patients with AD still lacks comprehensive investigation and solid imaging data support.

Objective: We explored whether WMHs can promote the pathological process of AD by aggravating atrophy in specific brain regions and tried to explain the regional specificity of these relationships.

Methods: A sample of 240 adults including 180 normal controls (NCs) and 80 cases with AD were drawn from the ADNI database. T1-weighted magnetic resonance imaging (MRI) and T2-weighted fluid-attenuated MRI of the participants were downloaded and were analyzed using AccuBrain^® to generate the quantitative ratio of WMHs (WMHr, WMH volumes corrected by intracranial volume) and regional brain atrophy. We also divided WMHr into periventricular WMHr (PVWMHr) and deep WMHr (DWMHr) for the purpose of this study. The Cholinergic Pathways Hyperintensities Scale (CHIPS) scores were conducted by two evaluators. Independent t-test, Mann-Whitney U test, or χ² test were used to compare the demographic characteristics, and Spearman correlation coefficient values were used to determine the association between WMHs and different regions of brain atrophy.

Results: Positive association between WMHr and quantitative medial temporal lobe atrophy (QMTA) (r _s = 0.281, p = 0.011), temporal lobe atrophy (r _s = 0.285, p = 0.011), and insular atrophy (r _s = 0.406, p < 0.001) was found in the AD group before Bonferroni correction. PVWMHr contributed to these correlations. By separately analyzing the relationship between PVWMHr and brain atrophy, we found that there were still positive correlations after correction in QMTA (r _s = 0.325, p = 0.003), temporal lobe atrophy (r _s = 0.298, p = 0.007), and insular atrophy (r _s = 0.429, p < 0.001) in AD group.

Conclusion: WMH severity tends to be associated with regional brain atrophy in patients with AD, especially with medial temporal lobe, temporal lobe, and insular lobe atrophy. PVWMHs were devoted to these correlations.

Keywords: Alzheimer's disease; brain atrophy; cholinergic pathway; magnetic resonance imaging; white matter hyperintensities.