尸检证实的额颞叶变性和阿尔茨海默病中的脑白质高信号。
White matter hyperintensities in autopsy-confirmed frontotemporal lobar degeneration and Alzheimer's disease.
机构信息
Cognitive & Movement Disorders Clinic, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room A4 42, Toronto, ON, M4N 3M5, Canada.
L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
出版信息
Alzheimers Res Ther. 2021 Jul 13;13(1):129. doi: 10.1186/s13195-021-00869-6.
BACKGROUND
We aimed to systematically describe the burden and distribution of white matter hyperintensities (WMH) and investigate correlations with neuropsychiatric symptoms in pathologically proven Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD).
METHODS
Autopsy-confirmed cases were identified from the Sunnybrook Dementia Study, including 15 cases of AD and 58 cases of FTLD (22 FTLD-TDP cases; 10 FTLD-Tau [Pick's] cases; 11 FTLD-Tau Corticobasal Degeneration cases; and 15 FTLD-Tau Progressive Supranuclear Palsy cases). Healthy matched controls (n = 35) were included for comparison purposes. Data analyses included ANCOVA to compare the burden of WMH on antemortem brain MRI between groups, adjusted linear regression models to identify associations between WMH burden and neuropsychiatric symptoms, and image-guided pathology review of selected areas of WMH from each pathologic group.
RESULTS
Burden and regional distribution of WMH differed significantly between neuropathological groups (F = 2.67, P' = 0.029), with the FTLD-TDP group having the highest mean volume globally (8032 ± 8889 mm) and in frontal regions (4897 ± 6163 mm). The AD group had the highest mean volume in occipital regions (468 ± 420 mm). Total score on the Neuropsychiatric Inventory correlated with bilateral frontal WMH volume (β = 0.330, P = 0.006), depression correlated with bilateral occipital WMH volume (β = 0.401, P < 0.001), and apathy correlated with bilateral frontal WMH volume (β = 0.311, P = 0.009), all corrected for the false discovery rate. Image-guided neuropathological assessment of selected cases with the highest burden of WMH in each pathologic group revealed presence of severe gliosis, myelin pallor, and axonal loss, but with no distinguishing features indicative of the underlying proteinopathy.
CONCLUSIONS
These findings suggest that WMH are associated with neuropsychiatric manifestations in AD and FTLD and that WMH burden and regional distribution in neurodegenerative disorders differ according to the underlying neuropathological processes.
背景
我们旨在系统描述经病理证实的阿尔茨海默病（AD）和额颞叶变性（FTLD）患者的脑白质高信号（WMH）的负担和分布，并探讨其与神经精神症状的相关性。
方法
从 Sunnybrook 痴呆研究中确定了尸检确诊的病例，包括 15 例 AD 病例和 58 例 FTLD 病例（22 例 FTLD-TDP 病例；10 例 FTLD-Tau[Pick's]病例；11 例 FTLD-Tau 皮质基底节变性病例；15 例 FTLD-Tau 进行性核上性麻痹病例）。纳入了 35 例健康匹配对照者用于比较。数据分析包括协方差分析（ANCOVA）以比较各组间脑 MRI 上 WMH 的负担，以及识别 WMH 负担与神经精神症状之间的关联的线性回归模型，和对每个病理组的选定 WMH 区域进行基于图像的病理学复查。
结果
WMH 的负担和区域分布在神经病理学组之间存在显著差异（F = 2.67，P' = 0.029），FTLD-TDP 组在全球范围内（8032 ± 8889mm）和额区（4897 ± 6163mm）的平均体积最高。AD 组在枕区的平均体积最高（468 ± 420mm）。神经精神疾病问卷的总分与双侧额区 WMH 体积呈正相关（β = 0.330，P = 0.006），抑郁与双侧枕区 WMH 体积呈正相关（β = 0.401，P < 0.001），而淡漠与双侧额区 WMH 体积呈正相关（β = 0.311，P = 0.009），所有结果均校正了假发现率。对每个病理组中 WMH 负担最高的选定病例进行基于图像的病理学评估显示存在严重的神经胶质增生、髓鞘苍白和轴索丢失，但没有表明潜在蛋白病的特征性表现。
结论
这些发现表明，WMH 与 AD 和 FTLD 的神经精神表现有关，且神经退行性疾病的 WMH 负担和区域分布根据潜在的神经病理学过程而不同。
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