Hee Jin Kim1, Kiho Im1, Hunki Kwon1, Jong-Min Lee1, Changsoo Kim1, Yeo Jin Kim1, Na-Yeon Jung1, Hanna Cho1, Byoung Seok Ye1, Young Noh1, Geon Ha Kim1, En-Da Ko1, Jae Seung Kim1, Yearn Seong Choe1, Kyung Han Lee1, Sung Tae Kim1, Jae Hong Lee1, Michael Ewers1, Michael W Weiner1, Duk L Na1, Sang Won Seo2. 1. From the Departments of Neurology (H.J.K., Y.J.K., N.-Y.J., E.-D.K., D.L.N., S.W.S.), Nuclear Medicine (Y.S.C., K.H.L.), and Radiology (S.T.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Neuroscience Center (H.J.K., Y.J.K., N.-Y.J., E.-D.K., D.L.N., S.W.S.), Samsung Medical Center, Seoul, Korea; Division of Newborn Medicine (K.I.), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Biomedical Engineering (H.K., J.-M.L.), Hanyang University, Seoul, Korea; Division of Preventive Medicine (C.K.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Departments of Preventive Medicine (C.K.) and Neurology (B.S.Y.), and Department of Neurology, Gangnam Severance Hospital (H.C.), Yonsei University College of Medicine, Seoul; Department of Neurology (Y.N.), Gachon University Gil Medical Center, Incheon; Ewha Womans University Mokdong Hospital (G.H.K.), Ewha Womans University School of Medicine, Seoul; Departments of Nuclear Medicine (J.S.K.) and Neurology (J.H.L.), University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; Institute for Stroke and Dementia Research (M.E.), Ludwig-Maximilians-University, Munich, Germany; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), University of California, San Francisco; Department of Clinical Research Design and Evaluation (D.L.N., S.W.S.), SAIHST, Sungkyunkwan University, Seoul, Korea. 2. From the Departments of Neurology (H.J.K., Y.J.K., N.-Y.J., E.-D.K., D.L.N., S.W.S.), Nuclear Medicine (Y.S.C., K.H.L.), and Radiology (S.T.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; Neuroscience Center (H.J.K., Y.J.K., N.-Y.J., E.-D.K., D.L.N., S.W.S.), Samsung Medical Center, Seoul, Korea; Division of Newborn Medicine (K.I.), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Biomedical Engineering (H.K., J.-M.L.), Hanyang University, Seoul, Korea; Division of Preventive Medicine (C.K.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Departments of Preventive Medicine (C.K.) and Neurology (B.S.Y.), and Department of Neurology, Gangnam Severance Hospital (H.C.), Yonsei University College of Medicine, Seoul; Department of Neurology (Y.N.), Gachon University Gil Medical Center, Incheon; Ewha Womans University Mokdong Hospital (G.H.K.), Ewha Womans University School of Medicine, Seoul; Departments of Nuclear Medicine (J.S.K.) and Neurology (J.H.L.), University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; Institute for Stroke and Dementia Research (M.E.), Ludwig-Maximilians-University, Munich, Germany; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), University of California, San Francisco; Department of Clinical Research Design and Evaluation (D.L.N., S.W.S.), SAIHST, Sungkyunkwan University, Seoul, Korea. sangwonseo@empal.com.
Abstract
BACKGROUND: We tested our hypothesis that the white matter network might mediate the effect of amyloid and small vessel disease (SVD) on cortical thickness and/or cognition. METHODS: We prospectively recruited 232 patients with cognitive impairment. Amyloid was assessed using Pittsburgh compound B-PET. SVD was quantified as white matter hyperintensity volume and lacune number. The regional white matter network connectivity was measured as regional nodal efficiency by applying graph theoretical analysis to diffusion tensor imaging data. We measured cortical thickness and performed neuropsychological tests. RESULTS: SVD burden was associated with decreased nodal efficiency in the bilateral frontal, lateral temporal, lateral parietal, and occipital regions. Path analyses showed that the frontal nodal efficiency mediated the effect of SVD on the frontal atrophy and frontal-executive dysfunction. The temporoparietal nodal efficiency mediated the effect of SVD on the temporoparietal atrophy and memory dysfunction. However, Pittsburgh compound B retention ratio affected cortical atrophy and cognitive impairment without being mediated by nodal efficiency. CONCLUSIONS: We suggest that a disrupted white matter network mediates the effect of SVD, but not amyloid, on specific patterns of cortical atrophy and/or cognitive impairment. Therefore, our findings provide insight to better understand how amyloid and SVD burden can give rise to brain atrophy or cognitive impairment in specific patterns.
BACKGROUND: We tested our hypothesis that the white matter network might mediate the effect of amyloid and small vessel disease (SVD) on cortical thickness and/or cognition. METHODS: We prospectively recruited 232 patients with cognitive impairment. Amyloid was assessed using Pittsburgh compound B-PET. SVD was quantified as white matter hyperintensity volume and lacune number. The regional white matter network connectivity was measured as regional nodal efficiency by applying graph theoretical analysis to diffusion tensor imaging data. We measured cortical thickness and performed neuropsychological tests. RESULTS:SVD burden was associated with decreased nodal efficiency in the bilateral frontal, lateral temporal, lateral parietal, and occipital regions. Path analyses showed that the frontal nodal efficiency mediated the effect of SVD on the frontal atrophy and frontal-executive dysfunction. The temporoparietal nodal efficiency mediated the effect of SVD on the temporoparietal atrophy and memory dysfunction. However, Pittsburgh compound B retention ratio affected cortical atrophy and cognitive impairment without being mediated by nodal efficiency. CONCLUSIONS: We suggest that a disrupted white matter network mediates the effect of SVD, but not amyloid, on specific patterns of cortical atrophy and/or cognitive impairment. Therefore, our findings provide insight to better understand how amyloid and SVD burden can give rise to brain atrophy or cognitive impairment in specific patterns.
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