Byoung Seok Ye1, Sang Won Seo1, Jung-Hyun Kim1, Geon Ha Kim1, Hanna Cho1, Young Noh1, Hee Jin Kim1, Cindy W Yoon1, Sook-Young Woo1, Sook Hui Kim1, Hee Kyung Park1, Sung Tae Kim1, Yearn Seong Choe1, Kyung Han Lee1, Jae Seung Kim1, Seung Jun Oh1, Changsoo Kim1, Michael Weiner1, Jae-Hong Lee1, Duk L Na2. 1. From the Departments of Neurology (B.S.Y., S.W.S., J.-H.K., H.J.K., D.L.N.), Radiology (S.T.K.), and Nuclear Medicine (Y.S.C., K.H.L.), Samsung Medical Center, Sungkyunkwan University School of Medicine; the Departments of Neurology (B.S.Y.) and Preventive Medicine (C.K.), Yonsei University College of Medicine; the Neuroscience Center (S.W.S., H.J.K., D.L.N.), Samsung Medical Center; the Ewha Womans University School of Medicine (G.H.K.); the Department of Neurology (H.C.), Yonsei University Gangnam Hospital, Seoul; the Department of Neurology (Y.N.), Gachon University Gil Medical Center; the Department of Neurology (C.W.Y.), Inha University School of Medicine, Incheon; the Biostatistics Team (S.-y.W.), Samsung Biomedical Research Institute; Merck, Sharp, and Dohme (MSD) (S.H.K.), Seoul; the Department of Neurology (H.K.P.), Inje University Ilsan Paik Hospital, Goyang; the Departments of Nuclear Medicine (J.S.K., S.J.O.) and Neurology (J.-H.L.), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; and Center for Imaging of Neurodegenerative Disease (M.W.), University of California, San Francisco. 2. From the Departments of Neurology (B.S.Y., S.W.S., J.-H.K., H.J.K., D.L.N.), Radiology (S.T.K.), and Nuclear Medicine (Y.S.C., K.H.L.), Samsung Medical Center, Sungkyunkwan University School of Medicine; the Departments of Neurology (B.S.Y.) and Preventive Medicine (C.K.), Yonsei University College of Medicine; the Neuroscience Center (S.W.S., H.J.K., D.L.N.), Samsung Medical Center; the Ewha Womans University School of Medicine (G.H.K.); the Department of Neurology (H.C.), Yonsei University Gangnam Hospital, Seoul; the Department of Neurology (Y.N.), Gachon University Gil Medical Center; the Department of Neurology (C.W.Y.), Inha University School of Medicine, Incheon; the Biostatistics Team (S.-y.W.), Samsung Biomedical Research Institute; Merck, Sharp, and Dohme (MSD) (S.H.K.), Seoul; the Department of Neurology (H.K.P.), Inje University Ilsan Paik Hospital, Goyang; the Departments of Nuclear Medicine (J.S.K., S.J.O.) and Neurology (J.-H.L.), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; and Center for Imaging of Neurodegenerative Disease (M.W.), University of California, San Francisco. dukna@skku.edu dukna@naver.com.
Abstract
OBJECTIVE: To determine the independent and synergistic effects of amyloid and small vessel disease (SVD) burden on longitudinal cognitive decline in patients with subcortical vascular dementia (SVaD). METHODS: A longitudinal cohort study was conducted involving patients from outpatient clinics of 2 tertiary referral centers. Sixty-one patients with SVaD were prospectively recruited and underwent MRI, 11C-Pittsburgh compound B (PiB) PET at baseline, and a 3-year annual neuropsychological follow-up. Effects of PiB positivity and SVD markers (white matter hyperintensities [WMH], lacunes, and microbleeds) on longitudinal cognitive decline were evaluated using generalized estimation equation after controlling for age, sex, education, APOE4 allele, and follow-up interval. RESULTS: When individual neuropsychological tests were used as outcome measures, PiB positivity was associated with faster cognitive decline in attention, visuospatial, visual memory, and global cognition function. Higher WMH burden was associated with faster cognitive decline in attention, visuospatial, visual recognition memory, and semantic/phonemic fluency function, whereas lacunes and microbleeds had no significant effects. When global dementia rating (Clinical Dementia Rating sum of boxes) was considered as an outcome measure, however, only PiB positivity was associated with faster cognitive decline. Significant interactions between PiB positivity and higher SVD burden were found to affect cognitive decline in semantic word fluency (from WMH burden) and global dementia rating (from microbleed burden). CONCLUSIONS: In SVaD patients, amyloid burden, independently or interactively with SVD, contributed to longitudinal cognitive decline. Amyloid deposition was the strongest poor prognostic factor.
OBJECTIVE: To determine the independent and synergistic effects of amyloid and small vessel disease (SVD) burden on longitudinal cognitive decline in patients with subcortical vascular dementia (SVaD). METHODS: A longitudinal cohort study was conducted involving patients from outpatient clinics of 2 tertiary referral centers. Sixty-one patients with SVaD were prospectively recruited and underwent MRI, 11C-Pittsburgh compound B (PiB) PET at baseline, and a 3-year annual neuropsychological follow-up. Effects of PiB positivity and SVD markers (white matter hyperintensities [WMH], lacunes, and microbleeds) on longitudinal cognitive decline were evaluated using generalized estimation equation after controlling for age, sex, education, APOE4 allele, and follow-up interval. RESULTS: When individual neuropsychological tests were used as outcome measures, PiB positivity was associated with faster cognitive decline in attention, visuospatial, visual memory, and global cognition function. Higher WMH burden was associated with faster cognitive decline in attention, visuospatial, visual recognition memory, and semantic/phonemic fluency function, whereas lacunes and microbleeds had no significant effects. When global dementia rating (Clinical Dementia Rating sum of boxes) was considered as an outcome measure, however, only PiB positivity was associated with faster cognitive decline. Significant interactions between PiB positivity and higher SVD burden were found to affect cognitive decline in semantic word fluency (from WMH burden) and global dementia rating (from microbleed burden). CONCLUSIONS: In SVaD patients, amyloid burden, independently or interactively with SVD, contributed to longitudinal cognitive decline. Amyloid deposition was the strongest poor prognostic factor.
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