Neuropathological findings in multiple system atrophy with cognitive impairment
Neuropathological findings in multiple system atrophy with cognitive impairment
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DOI：
10.1007/s00702-020-02201-2
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发表时间：
2020-05-04
影响因子：
3.3
通讯作者：
Jellinger, Kurt A.
中科院分区：
文献类型：
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作者：
Jellinger, Kurt A.
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，但在 MSA 中并不罕见。据报道，高达 47% 的 MSA 患者患有轻度认知障碍 (MCI)，而严重痴呆则很少见。我们将 48 例经尸检证实的 MSA 病例的临床 CI 与神经病理学结果联系起来。这项回顾性研究包括 33 例帕金森病为主的 MSA (MSA-P) 和 15 例小脑性共济失调为主的 MSA (MSA-C) 病例（平均死亡年龄 60.5 +/- 7.8；范围 46-82 岁）。然而，认知状态是根据医院图表进行评估的，没有进行全面的神经心理学测试。神经病理学检查，除了 MSA 病理分级外，还包括对 Lewy 和阿尔茨海默病相关共同病理的半定量评估。他们的发病率与 143 名年龄匹配的对照者（平均年龄 60.5 +/- 7.6 岁）进行了比较。报告的 10 例 MCI（20.8%）中，只有 3 例与中度皮质 tau 蛋白病理相关； 7 名患者 (14.5%) 中度 CI 与皮质淀粉样斑块相关，6 名患者中度中度皮质 tau 病理相关，其中 1 名患者可能与原发性年龄相关 tau 蛋白病 (PART) 相关；一位患有严重痴呆症的 82 岁女性表现出完全的阿尔茨海默病。在 8 例病例中观察到皮质淀粉样斑块，其中 3 例没有 tau 病理，与临床 MCI 相关，5 例中皮质 Lewy 病理也与此相关。两例患有皮质路易体病理和神经炎 Braak II 期和 III 期的病例，以及三例患有 Braak IV 期但无皮质路易体的病例，显示出中度 CI。在 4 例病例中观察到的皮质 Lewy 病理学与临床 CI 无关。 77.1% 的 MSA 病例没有阿尔茨海默病型病变，而对照组为 42%；而 MSA 队列中的 Lewy 病理学 (22.9%) 显着高于对照组 (8.4%)，均 p < 0.001。据报道，35.3% 的 MSA 患者患有轻度至中度 CI，其年龄显着高于无 CI 的患者，经常与皮质阿尔茨海默病（Braak III 期和 IV 期）和 Lewy 病理相关，而只有一名患有严重痴呆的患者完全发展为阿尔茨海默病。鉴于在有限的 MSA 患者系列中的这些发现，有必要进行进一步的研究来阐明 MSA 认知障碍的病理基础。
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.