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IF 3.4 2区医学 Q2 NEUROIMAGING

Neuroimage-Clinical Pub Date : 2024-12-07 DOI:10.1016/j.nicl.2024.103714

Jesse S Cohen, Jeffrey Phillips, Sandhitsu R Das, Christopher A Olm, Hamsanandini Radhakrishnan, Emma Rhodes, Katheryn A Q Cousins, Sharon X Xie, Ilya M Nasrallah, Paul A Yushkevich, David A Wolk, Edward B Lee, Daniel Weintraub, David J Irwin, Corey T McMillan

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引用次数: 0

摘要

背景：路易体失调症（LBD）包括帕金森病（PD）、帕金森病痴呆（PDD）和路易体痴呆（DLB），以α-突触核蛋白病理学为特征，但往往伴有阿尔茨海默病（AD）神经病理学改变（ADNC）。内侧颞叶（MTL）是 tau 累积和 AD 相关神经变性的主要部位。然而，目前还不清楚LBD（LBD/AD+）中的AD共病理学在多大程度上导致了MTL特异性变性模式。我们在生物标志物支持或尸检证实的LBD和LBD/AD+患者中采用T1加权（T1w）MRI的MTL亚区域分割策略，研究LBD/AD+共存病理对神经退行性变的解剖学影响：我们研究了167名临床诊断为LBD（PD，n = 124 (74.3%)；PDD，n = 11 (6.6%)；DLB，n = 32 (19.2%)）且有T1w MRI和AD生物标志物或尸检证据表明有ADNC的患者。根据ADNC病理学的分级证据，进一步将个体生物分类为LBD/AD+：1）AD "中度 "或 "高度"（ABC神经病理学标准）（n = 39 (23.4%)）；2）淀粉样蛋白PET阳性（n = 2 (1.2%)）；或3）CSF β-淀粉样蛋白1-42 结果：与LBD/AD-相比，除海马后部外，LBD/AD+在所有MTL亚区域的体积/厚度都有所下降。布罗德曼第 35 区（BA35）（Cohen's d = 0.62，p = 0.002，β = 0.107 ± 0.034）和内侧皮层（ERC）（Cohen's d = 0.56，p = 0.006，β = 0.088 ± 0.031）的效应大小最大。海马旁皮层（PHC）（Cohen's d = 0.5，p = 0.012，β = 0.082 ± 0.033）、BA36（Cohen's d = 0.47，p = 0.021，β = 0.090 ± 0.039）和海马前部（Cohen's d = 0.45，p = 0.029，β = 111.790 ± 50.595）的差异较小。言语记忆得分与海马前部和后部、BA35、ERC和PHC的体积/厚度呈正相关，而视觉空间记忆仅与BA35呈正相关。在进行尸检的参与者子集中，较低的ERC体积与较高的ERC tau负荷相关（调整后的几率比0.013，95 % CI [0.0002，0.841]，未校正p = 0.041）：与 LBD/AD- 相比，LBD/AD+ 在多个 MTL 亚区有更多的 T1w MRI 萎缩证据。MTL亚区的萎缩与记忆表现和tau病理负荷有关。观察到的萎缩模式基本符合AD Braak分期的预期，但海马后部除外。需要进行纵向研究来验证假设的神经退行性病变扩散。

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Posterior hippocampal sparing in Lewy body disorders with Alzheimer's copathology: An in vivo MRI study.

Background: Lewy body disorders (LBD), encompassing Parkinson disease (PD), PD dementia (PDD), and dementia with Lewy bodies (DLB), are characterized by alpha-synuclein pathology but often are accompanied by Alzheimer's disease (AD) neuropathological change (ADNC). The medial temporal lobe (MTL) is a primary locus of tau accumulation and associated neurodegeneration in AD. However, it is unclear the extent to which AD copathology in LBD (LBD/AD+) contributes to MTL-specific patterns of degeneration. We employ a MTL subregional segmentation strategy of T1-weighted (T1w) MRI in biomarker-supported or autopsy-confirmed LBD and LBD/AD+ to investigate the anatomic consequences of co-occurring LBD/AD+ pathology on neurodegeneration.

Methods: We studied 167 individuals with clinical diagnoses of LBD (PD, n = 124 (74.3 %); PDD, n = 11 (6.6 %); DLB, n = 32 (19.2 %)) with available T1w MRI and AD biomarkers or autopsy evidence of ADNC. Individuals were further biologically classified as LBD/AD+ based on hierarchical evidence of ADNC pathology: 1) AD "intermediate" or "high" by ABC neuropathologic criteria (n = 39 (23.4 %)); 2) positive amyloid PET (n = 2 (1.2 %)); or 3) CSF β-amyloid_1-42 < 185.7 pg/mL n = 126 (75.4 %)). The T1 Automated Segmentation of Hippocampal Subfields (ASHS) pipeline was used to compute volume and thickness measurements of MTL subregions in LBD/AD- and LBD/AD+. Linear regression tested the association of AD copathology and subregion volume/thickness, covarying for age and sex, and intracranial volume for volume measurements. Secondary analyses correlated MTL subregional volume/thickness with cognition and neuropathology.

Results: LBD/AD+ had decreased volume/thickness compared to LBD/AD- in all MTL subregions except posterior hippocampus. The greatest effect sizes were seen in Brodmann Area 35 (BA35) (Cohen's d = 0.62, p = 0.002, β = 0.107 ± 0.034), and entorhinal cortex (ERC) (Cohen's d = 0.56, p = 0.006, β = 0.088 ± 0.031). Smaller differences were seen in the parahippocampal cortex (PHC) (Cohen's d = 0.5, p = 0.012, β = 0.082 ± 0.033), BA36 (Cohen's d = 0.47, p = 0.021, β = 0.090 ± 0.039) and anterior hippocampus (Cohen's d = 0.45, p = 0.029, β = 111.790 ± 50.595). Verbal memory scores positively correlated with volume/thickness in anterior and posterior hippocampus, BA35, ERC and PHC, while visuospatial memory positively correlated only in BA35. In the subset of participants with autopsy, lower ERC volume was associated with a higher tau load in ERC (adjusted odds ratio 0.013, 95 % CI [0.0002, 0.841], uncorrected p = 0.041).

Conclusions: Relative to LBD/AD-, LBD/AD+ has greater T1w MRI evidence of atrophy in multiple MTL subregions. Atrophy in MTL subregions associates with memory performance and tau pathological load. The observed pattern of atrophy largely follows expectation from AD Braak stages, except for posterior hippocampus. Longitudinal studies are needed to validate the hypothesized spread of neurodegeneration.

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来源期刊

Neuroimage-Clinical NEUROIMAGING-

CiteScore

7.50

自引率

4.80%

发文量

368

审稿时长

52 days

期刊介绍： NeuroImage: Clinical, a journal of diseases, disorders and syndromes involving the Nervous System, provides a vehicle for communicating important advances in the study of abnormal structure-function relationships of the human nervous system based on imaging. The focus of NeuroImage: Clinical is on defining changes to the brain associated with primary neurologic and psychiatric diseases and disorders of the nervous system as well as behavioral syndromes and developmental conditions. The main criterion for judging papers is the extent of scientific advancement in the understanding of the pathophysiologic mechanisms of diseases and disorders, in identification of functional models that link clinical signs and symptoms with brain function and in the creation of image based tools applicable to a broad range of clinical needs including diagnosis, monitoring and tracking of illness, predicting therapeutic response and development of new treatments. Papers dealing with structure and function in animal models will also be considered if they reveal mechanisms that can be readily translated to human conditions.