Institute of Clinical Neurobiology, Alberichgasse 5/13, 1150, Vienna, Austria.
J Neural Transm (Vienna). 2020 Jul;127(7):1031-1039. doi: 10.1007/s00702-020-02201-2. Epub 2020 May 4.
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.
认知障碍（CI）以前被认为是根据第二共识标准诊断多系统萎缩（MSA）的排除标准，但在 MSA 中并不少见。据报道，高达 47%的 MSA 患者存在轻度认知障碍（MCI），而严重痴呆则很少见。我们在 48 例经 autopsy 证实的 MSA 病例中研究了临床 CI 与神经病理学发现之间的关系。这项回顾性研究包括 33 例帕金森病为主型 MSA（MSA-P）和 15 例小脑共济失调为主型 MSA（MSA-C）病例（死亡时平均年龄 60.5±7.8；范围 46-82 岁）。认知状态是根据医院病历评估的，但没有进行全面的神经心理学测试。神经病理学检查除了对 MSA 病理进行分级外，还包括 Lewy 和阿尔茨海默氏症相关共病的半定量评估。将其发生率与 143 名年龄匹配的对照组（平均年龄 60.5±7.6 岁）进行比较。10 例（20.8%）报告的 MCI 仅与 3 例中度皮质 tau 病理学相关；7 例（14.5%）中度 CI 与皮质淀粉样斑块和皮质 tau 病理学各 6 例相关，1 例与可能的原发性年龄相关性 tau 病（PART）相关；一名 82 岁女性患有严重痴呆，表现出完全发育的阿尔茨海默病。观察到的 8 例皮质淀粉样斑块，其中 3 例无 tau 病理学，与临床 MCI 相关，5 例皮质 Lewy 病理学也与临床 MCI 相关。2 例皮质 Lewy 病理学和神经突 Braak 阶段 II 和 III，3 例 Braak 阶段 IV，无皮质 Lewy 体，表现出中度 CI。4 例观察到的皮质 Lewy 病理学与临床 CI 无关。与对照组的 42%相比，MSA 病例中无阿尔茨海默型病变的比例为 77.1%；而 MSA 队列中的 Lewy 病理学（22.9%）明显高于对照组（8.4%），两者均 p<0.001。在 MSA 患者中报告的轻度至中度 CI 占 35.3%，显著高于无 CI 的患者，这些患者常与皮质阿尔茨海默氏症（Braak 阶段 III 和 IV）和 Lewy 病理学相关，而只有 1 例严重痴呆患者具有完全发育的阿尔茨海默病。鉴于 MSA 患者的这一有限系列研究结果，有必要进一步研究以阐明 MSA 认知障碍的病理基础。
