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.
Neurology. 2022 Mar 1;98(9):e947-e957. doi: 10.1212/WNL.0000000000013277. Epub 2021 Dec 30.
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.
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 F-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.
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.
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.
胆碱能神经退行性变和β-淀粉样蛋白导致阿尔茨海默病（AD）和路易体病（LBD）的脑萎缩和认知功能障碍，但它们之间的关系尚未进行比较评估。
在这项横断面研究中，我们招募了 28 名正常对照（NC）、55 名 AD 轻度认知障碍（MCI）患者、34 名 AD 痴呆患者、28 名 LBD MCI 患者和 51 名 LBD 痴呆患者。参与者接受认知评估、脑 MRI 测量基底前脑（BF）体积和全脑皮质厚度（CTh）、F-氟比苯（FBB）PET 测量标准化摄取值比（SUVR）。使用一般线性模型和路径分析，我们分别评估了 FBB-SUVR 与 AD 谱（AD 和 NC）和 LBD 谱（LBD 和 NC）中 BF 体积与 CTh 或认知功能障碍之间的关联。协变量包括年龄、性别、教育程度、深部和脑室周围白质高信号、脑容量、高血压、糖尿病和高脂血症。
BF 体积介导了 FBB-SUVR 与 AD 和 LBD 谱中 CTh 之间的关联，而 FBB-SUVR 仅在 LBD 谱中与 BF 体积独立相关与 CTh 相关。仅在 LBD 组中观察到 FBB-SUVR 与 CTh 之间存在显著相关性。FBB-SUVR 与 AD 和 LBD 谱中广泛的认知功能障碍独立相关，特别是在记忆域（AD 谱的标准化β[B]=-0.60，LBD 谱的 B=-0.33）。在 AD 谱中，BF 体积与记忆功能障碍相关（B=0.18），CTh 与语言（B=0.21）和执行（B=0.23）功能障碍相关。然而，在 LBD 谱中，BF 体积和 CTh 与广泛的认知功能障碍独立相关。
在 AD 和 LBD 谱中存在共同的β-淀粉样蛋白相关退行性机制，伴有或不伴有 BF 的介导，而 BF 萎缩与认知功能障碍的关联更为显著，并且在 LBD 谱中存在局部的β-淀粉样蛋白-皮质萎缩相互作用。
