Joanna Su Xian Chong1, Hyemin Jang1, Hee Jin Kim1, Kwun Kei Ng1, Duk L Na1, Jae Hong Lee1, Sang Won Seo2, Juan Zhou2. 1. From the Centre for Cognitive Neuroscience (J.S.X.C., K.K.N., J.Z.), Neuroscience and Behavioural Disorders Programme, Duke-National University of Singapore Medical School; Department of Neurology (H.J., H.J.K., D.L.N., S.W.S.), Samsung Medical Center, Sungkyunkwan University School of Medicine; Department of Neurology (J.H.L.), Asan Medical Center, Ulsan University School of Medicine, Seoul, Korea; and Clinical Imaging Research Centre, National University of Singapore (J.Z.). 2. From the Centre for Cognitive Neuroscience (J.S.X.C., K.K.N., J.Z.), Neuroscience and Behavioural Disorders Programme, Duke-National University of Singapore Medical School; Department of Neurology (H.J., H.J.K., D.L.N., S.W.S.), Samsung Medical Center, Sungkyunkwan University School of Medicine; Department of Neurology (J.H.L.), Asan Medical Center, Ulsan University School of Medicine, Seoul, Korea; and Clinical Imaging Research Centre, National University of Singapore (J.Z.). helen.zhou@duke-nus.edu.sg sangwonseo@empal.com.
Abstract
OBJECTIVE: To examine the effects of baseline Alzheimer disease and cerebrovascular disease markers on longitudinal default mode network (DMN) and executive control network (ECN) functional connectivity (FC) changes in mild cognitive impairment (MCI). METHODS: We studied 30 patients with amnestic MCI (aMCI) and 55 patients with subcortical vascular MCI (svMCI) with baseline Pittsburgh Compound B (PiB)-PET scans and longitudinal MRI scans. Participants were followed up clinically with annual MRI for up to 4 years (aMCI: 26 with 2 timepoints, 4 with 3 timepoints; svMCI: 13 with 2 timepoints, 16 with 3 timepoints, 26 with 4 timepoints). RESULTS: β-Amyloid (Aβ) burden was associated with longitudinal DMN FC declines, while cerebrovascular burden was associated with longitudinal ECN FC changes. When patients were divided into PiB+ and PiB- groups, PiB+ patients showed longitudinal DMN FC declines, while patients with svMCI showed longitudinal ECN FC increases. Direct comparisons between the 2 groups without mixed pathology (aMCI PiB+ and svMCI PiB-) recapitulated this divergent pattern: aMCI PiB+ patients showed steeper longitudinal DMN FC declines, while svMCI PiB- patients showed steeper longitudinal ECN FC increases. Finally, using baseline PiB uptake and lacune numbers as continuous variables, baseline PiB uptake showed inverse U-shape associations with longitudinal DMN FC changes in both MCI subtypes, while baseline lacune numbers showed mainly inverse U-shape relationships with longitudinal ECN FC changes in patients with svMCI. CONCLUSIONS: Our findings underscore the divergent effects of Aβ and cerebrovascular burden on longitudinal FC changes in the DMN and ECN in the predementia stage, which reflect the underlying pathology and may be used to track early changes in Alzheimer disease and cerebrovascular disease.
OBJECTIVE: To examine the effects of baseline Alzheimer disease and cerebrovascular disease markers on longitudinal default mode network (DMN) and executive control network (ECN) functional connectivity (FC) changes in mild cognitive impairment (MCI). METHODS: We studied 30 patients with amnestic MCI (aMCI) and 55 patients with subcortical vascular MCI (svMCI) with baseline Pittsburgh Compound B (PiB)-PET scans and longitudinal MRI scans. Participants were followed up clinically with annual MRI for up to 4 years (aMCI: 26 with 2 timepoints, 4 with 3 timepoints; svMCI: 13 with 2 timepoints, 16 with 3 timepoints, 26 with 4 timepoints). RESULTS: β-Amyloid (Aβ) burden was associated with longitudinal DMN FC declines, while cerebrovascular burden was associated with longitudinal ECN FC changes. When patients were divided into PiB+ and PiB- groups, PiB+ patients showed longitudinal DMN FC declines, while patients with svMCI showed longitudinal ECN FC increases. Direct comparisons between the 2 groups without mixed pathology (aMCI PiB+ and svMCI PiB-) recapitulated this divergent pattern: aMCI PiB+ patients showed steeper longitudinal DMN FC declines, while svMCI PiB- patients showed steeper longitudinal ECN FC increases. Finally, using baseline PiB uptake and lacune numbers as continuous variables, baseline PiB uptake showed inverse U-shape associations with longitudinal DMN FC changes in both MCI subtypes, while baseline lacune numbers showed mainly inverse U-shape relationships with longitudinal ECN FC changes in patients with svMCI. CONCLUSIONS: Our findings underscore the divergent effects of Aβ and cerebrovascular burden on longitudinal FC changes in the DMN and ECN in the predementia stage, which reflect the underlying pathology and may be used to track early changes in Alzheimer disease and cerebrovascular disease.
Authors: Adeline Su Lyn Ng; Juan Wang; Kwun Kei Ng; Joanna Su Xian Chong; Xing Qian; Joseph Kai Wei Lim; Yi Jayne Tan; Alisa Cui Wen Yong; Russell Jude Chander; Shahul Hameed; Simon Kang Seng Ting; Nagaendran Kandiah; Juan Helen Zhou Journal: Alzheimers Res Ther Date: 2021-01-06 Impact factor: 6.982