Cognitive impairment (CI), previously considered an exclusion criterium for the diagnosis of multiple system atrophy (MSA) according to the second consensus criteria, is not uncommon in MSA. Mild cognitive impairment (MCI) has been reported in up to 47% of MSA patients, while severe dementia is rare. We related clinical CI with neuropathological findings in 48 autopsy-proven cases of MSA. This retrospective study included 33 parkinsonism predominant MSA (MSA-P), and 15 cerebellar ataxia-predominant MSA (MSA-C) cases (mean age at death 60.5 ± 7.8; range 46-82 years). Cognitive state was assessed from hospital charts, however, without comprehensive neuropsychological testing. Neuropathological examination, in addition to grading of the MSA pathologies, included semiquantitative assessment of Lewy and Alzheimer-related co-pathologies. Their incidence was compared with 143 age-matched controls (mean age 60.5 ± 7.6 years). MCI reported in ten cases (20.8%) was associated with moderate cortical tau pathology in only three; moderate CI in seven patients (14.5%) was associated with cortical amyloid plaques and moderate cortical tau pathology in six each, and one with probable primary age-related tauopathy (PART); a female aged 82 years with severe dementia showed fully developed Alzheimer disease. Cortical amyloid plaques, observed in eight cases, three of them without tau pathology, were associated with clinical MCI, as was cortical Lewy pathology in five. Two cases with cortical Lewy pathology and neuritic Braak stages II and III, and three with Braak stage IV, without cortical Lewy bodies, had shown moderate CI. Cortical Lewy pathology observed in four cases was not associated with clinical CI. 77.1% of the MSA cases were free of Alzheimer-type lesions, compared to 42% of controls; while Lewy pathology in the MSA cohort (22.9%) was significantly higher than in the control group (8.4%) both p < 0.001. Mild-to-moderate CI, reported in 35.3% of MSA patients, being significantly older than those without CI, were frequently associated with cortical Alzheimer (Braak stages III and IV) and Lewy pathologies, while only one with severe dementia had fully developed Alzheimer disease. In view of these findings in a limited series of MSA patients, further studies to elucidate the pathological basis of cognitive impairment in MSA are warranted.

中文翻译：

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多系统萎缩伴认知障碍的神经病理学发现。

认知障碍 (CI) 以前被认为是根据第二个共识标准诊断多系统萎缩 (MSA) 的排除标准，在 MSA 中并不少见。据报道，多达 47% 的 MSA 患者出现轻度认知障碍 (MCI)，而严重的痴呆症很少见。我们将临床 CI 与 48 例经尸检证实的 MSA 病例的神经病理学发现联系起来。这项回顾性研究包括 33 例帕金森综合征为主的 MSA (MSA-P) 和 15 例小脑共济失调为主的 MSA (MSA-C) 病例（平均死亡年龄 60.5 ± 7.8 岁；范围 46-82 岁）。然而，认知状态是根据医院图表评估的，没有进行全面的神经心理学测试。除了 MSA 病理分级外，神经病理学检查还包括对路易和阿尔茨海默病相关共病的半定量评估。他们的发病率与 143 名年龄匹配的对照组（平均年龄 60.5 ± 7.6 岁）进行了比较。MCI 报告的 10 例 (20.8%) 仅与 3 例中度皮质 tau 病理相关；7 名患者 (14.5%) 的中度 CI 与皮质淀粉样蛋白斑块和中度皮质 tau 蛋白病理相关，每人 6 人，其中 1 人可能与原发性年龄相关的 tau 蛋白病变 (PART) 相关；一位患有严重痴呆症的 82 岁女性显示完全发展为阿尔茨海默病。在 8 个病例中观察到的皮质淀粉样蛋白斑块（其中 3 个没有 tau 病理学）与临床 MCI 相关，5 个病例的皮质 Lewy 病理学也是如此。两例皮层路易氏病理和神经炎性 Braak II 期和 III 期病例和三例 Braak IV 期病例，无皮质路易体，显示中度 CI。在四个病例中观察到的皮质路易病理学与临床 CI 无关。77.1% 的 MSA 病例没有阿尔茨海默型病变，而对照组为 42%；而 MSA 队列中的路易病理 (22.9%) 显着高于对照组 (8.4%)，两者 p < 0.001。据报道，35.3% 的 MSA 患者出现轻度至中度 CI，明显比没有 CI 的患者年龄大，经常与皮质阿尔茨海默病（Braak III 和 IV 期）和路易病有关，而只有一名患有严重痴呆症的患者完全发展为阿尔茨海默病疾病。鉴于在有限系列 MSA 患者中的这些发现，有必要进一步研究以阐明 MSA 认知障碍的病理基础。而 MSA 队列中的路易病理 (22.9%) 显着高于对照组 (8.4%)，两者 p < 0.001。据报道，35.3% 的 MSA 患者出现轻度至中度 CI，明显比没有 CI 的患者年龄大，经常与皮质阿尔茨海默病（Braak III 和 IV 期）和路易病有关，而只有一名患有严重痴呆症的患者完全发展为阿尔茨海默病疾病。鉴于在有限系列 MSA 患者中的这些发现，有必要进一步研究以阐明 MSA 认知障碍的病理基础。而 MSA 队列中的路易病理 (22.9%) 显着高于对照组 (8.4%)，两者 p < 0.001。据报道，35.3% 的 MSA 患者出现轻度至中度 CI，明显比没有 CI 的患者年龄大，经常与皮质阿尔茨海默病（Braak III 和 IV 期）和路易病有关，而只有一名患有严重痴呆症的患者完全发展为阿尔茨海默病疾病。鉴于在有限系列 MSA 患者中的这些发现，有必要进一步研究以阐明 MSA 认知障碍的病理基础。经常与皮质阿尔茨海默病（Braak III 期和 IV 期）和路易病有关，而只有严重痴呆症的人完全发展为阿尔茨海默病。鉴于在有限系列 MSA 患者中的这些发现，有必要进一步研究以阐明 MSA 认知障碍的病理基础。经常与皮质阿尔茨海默病（Braak III 期和 IV 期）和路易病有关，而只有严重痴呆症的人完全发展为阿尔茨海默病。鉴于在有限系列 MSA 患者中的这些发现，有必要进一步研究以阐明 MSA 认知障碍的病理基础。