Han Soo Yoo1, Seun Jeon1, Enrica Cavedo1, MinJin Ko1, Mijin Yun1, Phil Hyu Lee1, Young H Sohn1, Michel J Grothe1, Stefan Teipel1, Harald Hampel1, Alan C Evans1, Byoung Seok Ye2. 1. From the Department of Neurology (H.S.Y., S.J., P.H.L., Y.H.S., B.S.Y.), Brain Research Institute (S.J.), Severance Biomedical Science Institute (M.J.K.), and Department of Nuclear Medicine (M.Y.), Yonsei University College of Medicine, Seoul, South Korea; Sorbonne University (E.C., H.H.), GRC N0. 21, Alzheimer Precision Medicine, AP-HP, Pitié-Salpêtrière Hospital; Qynapse (E.C.), Paris, France; German Center for Neurodegenerative Diseases (DZNE)-Rostock/Greifswald (M.J.G., S.T.), Rostock, Germany; Unidad de Trastornos del Movimiento (M.J.G.), Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain; Department of Psychosomatic Medicine (S.T.), University Medicine Rostock, Germany; and McGill Center for Integrative Neuroscience (A.C.E.), Montreal Neurological Institute, McGill University, Quebec, Canada. 2. From the Department of Neurology (H.S.Y., S.J., P.H.L., Y.H.S., B.S.Y.), Brain Research Institute (S.J.), Severance Biomedical Science Institute (M.J.K.), and Department of Nuclear Medicine (M.Y.), Yonsei University College of Medicine, Seoul, South Korea; Sorbonne University (E.C., H.H.), GRC N0. 21, Alzheimer Precision Medicine, AP-HP, Pitié-Salpêtrière Hospital; Qynapse (E.C.), Paris, France; German Center for Neurodegenerative Diseases (DZNE)-Rostock/Greifswald (M.J.G., S.T.), Rostock, Germany; Unidad de Trastornos del Movimiento (M.J.G.), Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain; Department of Psychosomatic Medicine (S.T.), University Medicine Rostock, Germany; and McGill Center for Integrative Neuroscience (A.C.E.), Montreal Neurological Institute, McGill University, Quebec, Canada. romel79@gmail.com.
Abstract
OBJECTIVE: Cholinergic degeneration and β-amyloid contribute to brain atrophy and cognitive dysfunction in Alzheimer disease (AD) and Lewy body disease (LBD), but their relationship has not been comparatively evaluated. METHODS: In this cross-sectional study, we recruited 28 normal controls (NC), 55 patients with AD mild cognitive impairment (MCI), 34 patients with AD dementia, 28 patients with LBD MCI, and 51 patients with LBD dementia. Participants underwent cognitive evaluation, brain MRI to measure the basal forebrain (BF) volume and global cortical thickness (CTh), and 18F-florbetaben (FBB) PET to measure the standardized uptake value ratio (SUVR). Using general linear models and path analyses, we evaluated the association of FBB-SUVR and BF volume with CTh or cognitive dysfunction in the AD spectrum (AD and NC) and LBD spectrum (LBD and NC), respectively. Covariates included age, sex, education, deep and periventricular white matter hyperintensities, intracranial volume, hypertension, diabetes, and hyperlipidemia. RESULTS: BF volume mediated the association between FBB-SUVR and CTh in both the AD and LBD spectra, while FBB-SUVR was associated with CTh independently of BF volume only in the LBD spectrum. Significant correlation between voxel-wise FBB-SUVR and CTh was observed only in the LBD group. FBB-SUVR was independently associated with widespread cognitive dysfunction in both the AD and LBD spectra, especially in the memory domain (standardized beta [B] for AD spectrum = -0.60, B for LBD spectrum = -0.33). In the AD spectrum, BF volume was associated with memory dysfunction (B = 0.18), and CTh was associated with language (B = 0.21) and executive (B = 0.23) dysfunction. In the LBD spectrum, however, BF volume and CTh were independently associated with widespread cognitive dysfunction. CONCLUSIONS: There is a common β-amyloid-related degenerative mechanism with or without the mediation of BF in the AD and LBD spectra, while the association of BF atrophy with cognitive dysfunction is more profound and there is localized β-amyloid-cortical atrophy interaction in the LBD spectrum.
OBJECTIVE: Cholinergic degeneration and β-amyloid contribute to brain atrophy and cognitive dysfunction in Alzheimer disease (AD) and Lewy body disease (LBD), but their relationship has not been comparatively evaluated. METHODS: In this cross-sectional study, we recruited 28 normal controls (NC), 55 patients with AD mild cognitive impairment (MCI), 34 patients with AD dementia, 28 patients with LBD MCI, and 51 patients with LBD dementia. Participants underwent cognitive evaluation, brain MRI to measure the basal forebrain (BF) volume and global cortical thickness (CTh), and 18F-florbetaben (FBB) PET to measure the standardized uptake value ratio (SUVR). Using general linear models and path analyses, we evaluated the association of FBB-SUVR and BF volume with CTh or cognitive dysfunction in the AD spectrum (AD and NC) and LBD spectrum (LBD and NC), respectively. Covariates included age, sex, education, deep and periventricular white matter hyperintensities, intracranial volume, hypertension, diabetes, and hyperlipidemia. RESULTS: BF volume mediated the association between FBB-SUVR and CTh in both the AD and LBD spectra, while FBB-SUVR was associated with CTh independently of BF volume only in the LBD spectrum. Significant correlation between voxel-wise FBB-SUVR and CTh was observed only in the LBD group. FBB-SUVR was independently associated with widespread cognitive dysfunction in both the AD and LBD spectra, especially in the memory domain (standardized beta [B] for AD spectrum = -0.60, B for LBD spectrum = -0.33). In the AD spectrum, BF volume was associated with memory dysfunction (B = 0.18), and CTh was associated with language (B = 0.21) and executive (B = 0.23) dysfunction. In the LBD spectrum, however, BF volume and CTh were independently associated with widespread cognitive dysfunction. CONCLUSIONS: There is a common β-amyloid-related degenerative mechanism with or without the mediation of BF in the AD and LBD spectra, while the association of BF atrophy with cognitive dysfunction is more profound and there is localized β-amyloid-cortical atrophy interaction in the LBD spectrum.
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