Cognitive impairment in progressive supranuclear palsy is associated with tau burden.
Cognitive impairment in progressive supranuclear palsy is associated with tau burden.
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DOI：
10.1002/mds.27198
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Dickson DW
中科院分区：
文献类型：
--
作者：
Koga S;Parks A;Kasanuki K;Sanchez-Contreras M;Baker MC;Josephs KA;Ahlskog JE;Uitti RJ;Graff-Radford N;van Gerpen JA;Wszolek ZK;Rademakers R;Dickson DW
认知障碍是进行性核上性麻痹的核心特征之一。本研究旨在阐明进行性核上性麻痹患者的认知功能障碍及其病理基础。我们回顾性分析了121例尸检证实的进行性核上性麻痹患者的病历，以评估其认知功能障碍的模式和严重程度。37例患者的子集进行神经心理学评价作为其临床检查的一部分。在20个脆弱的大脑区域中对进行性核上性麻痹相关tau病理学（神经元缠结/前角、卷曲体、簇状星形胶质细胞和线）的负担进行半定量评分。还评估了可能与认知障碍相关的并发病理，如阿尔茨海默型病理。为了评估认知障碍的可能遗传风险因素，进行了APOE和MAPT的遗传分析。90例患者（74%）记录了基于神经系统评估的认知障碍。在神经心理学测试的一个亚组（N = 37）中，执行功能是受损最严重的认知领域。整体认知障碍指数（斯皮尔曼rho −0.49，P = 0.005）和执行功能与总tau蛋白负荷呈负相关（斯皮尔曼rho −0.51，P = 0.003），但与阿尔茨海默病型病理学无关。APOE ε4携带者有更严重的淀粉样病变，但总tau负荷和总体测试组合平均值与APOE ε4非携带者没有差异。进行性核上性麻痹中的认知障碍，最显著的是执行功能障碍，与进行性核上性麻痹相关的tau病理的严重程度相关。
Cognitive impairment is one of the core features of progressive supranuclear palsy. This study aimed to clarify the profile of cognitive impairment and its underlying pathology in progressive supranuclear palsy. We retrospectively reviewed medical records to evaluate the pattern and severity of cognitive impairment in 121 autopsy-confirmed progressive supranuclear palsy patients. A subset of 37 patients underwent neuropsychological evaluation as part of their clinical work-up. The burden of progressive supranuclear palsy-related tau pathology (neurofibrillary tangles/pretangles, coiled bodies, tufted astrocytes, and threads) was semi-quantitatively scored in 20 vulnerable brain regions. Concurrent pathologies potentially associated with cognitive impairment, such as Alzheimer-type pathology, were also assessed. To evaluate possible genetic risk factors for cognitive impairment, genetic analysis for APOE and MAPT was performed. Ninety patients (74%) had documented cognitive impairment based on neurologic evaluation. In a subgroup with neuropsychological testing (N = 37), executive functioning was the most severely impaired cognitive domain. A global cognitive impairment index (Spearman’s rho −0.49, P = 0.005) and executive functioning were negatively correlated with total tau burden (Spearman’s rho −0.51, P = 0.003), but not correlated with the Alzheimer-type pathology. APOE ε4 carriers had more severe amyloid pathology, but total tau burden and overall test battery mean was not different from APOE ε4 non-carriers. Cognitive impairment in progressive supranuclear palsy, most notably executive dysfunction, is associated with severity of progressive supranuclear palsy-related tau pathology.
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