Alpha-synucleinopathy and neuropsychological symptoms in a population-based cohort of the elderly.
Alpha-synucleinopathy and neuropsychological symptoms in a population-based cohort of the elderly.
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老年人同类的α-突触核病和神经心理学症状。
DOI：
10.1186/s13195-015-0101-x
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
MRC Cognitive Function and Ageing Neuropathology Study
中科院分区：
文献类型：
--
作者：
Zaccai J;Brayne C;Matthews FE;Ince PG;MRC Cognitive Function and Ageing Neuropathology Study
具有强选择性偏倚的研究表明，α-突触核蛋白病（AS）从延髓向上和向下扩散到神经轴，杏仁核主导的AS与阿尔茨海默病（AD）密切相关，并且大脑皮质的更严重参与与痴呆风险增加相关。本研究探讨了AS模式和观察到的神经心理学症状的人群代表性捐助者队列的大脑中的关联。对6个认知功能和衰老研究队列中的2个（剑桥郡和诺丁汉）捐赠的大脑进行了检查。超过80%的人死亡时年龄>80岁。受访者在生活中接受了认知能力下降和痴呆的前瞻性评估。在208个脑中进行tau和α-突触核蛋白的免疫细胞化学（使用Zymed Laboratories的LB 509），以根据路易体痴呆（DLB）共识建议建立Braak分期以及AS的模式和严重程度。研究了痴呆、使用剑桥认知检查测量的特定神经心理学测量、幻觉和帕金森病的存在。观察到4种AS模式：无AS病理（n = 92），遵循DLB共识指南的AS病理（n = 33，其中5种为“新皮质”），杏仁核主导型AS（n = 18）和其他AS模式（n = 33）。根据高/低神经元缠结（NFT）Braak分期将每组再细分。结果显示，痴呆和AS的这些模式之间没有关联，调整了NFT的存在与否。在黑质（比值比（OR）= 3.2; 95%置信区间（CI）0.5至15.5; P = 0.09）和杏仁核（OR = 3.0; 95% CI 0.7至12.3; P = 0.07）中，幻视风险与AS的相关性较弱。对皮层下区域幻听的分析也是类似的。在整个老年人群中，无论NFT病理的Braak阶段如何，AS都不会增加痴呆的风险。没有证据表明皮质区AS病理模式与幻觉风险相关。一般而言，使用这些方法测量AS本身是认知临床表型的关键决定因素的假设不被支持。
Studies with strong selection biases propose that alpha-synucleinopathy (AS) spreads upwards and downwards in the neuraxis from the medulla, that amygdala-dominant AS is strongly associated with Alzheimer’s disease (AD), and that a more severe involvement of the cerebral cortex is correlated with increasing risk of dementia. This study examines the association of AS patterns and observed neuropsychological symptoms in brains of a population-representative donor cohort. Brains donated in 2 out of 6 cognitive function and ageing study cohorts (Cambridgeshire and Nottingham) were examined. Over 80% were >80 years old at death. The respondents were evaluated prospectively in life for cognitive decline and dementia. Immunocytochemistry for tau and alpha-synuclein (using LB509 by Zymed Laboratories) was carried out in 208 brains to establish Braak stage and the pattern and severity of AS following the dementia with Lewy bodies (DLB) consensus recommendations. Dementia, specific neuropsychological measures as measured using the Cambridge cognitive examination, the presence of hallucinations and Parkinson’s disease were investigated. Four patterns of AS were observed: no AS pathology (n = 92), AS pathology following the DLB consensus guidelines (n = 33, of which five were ‘neocortical’), amygdala-predominant AS (n = 18), and other AS patterns (n = 33). Each group was subdivided according to high/low neurofibrillary tangles (NFT) Braak stage. Results showed no association between dementia and these patterns of AS, adjusting for the presence of NFT or not. The risk of visual hallucinations shows a weak association with AS in the substantia nigra (odds ratio (OR) = 3.2; 95% confidence interval (CI) 0.5 to 15.5; P = 0.09) and amygdala (OR = 3.0; 95% CI 0.7 to 12.3; P = 0.07). The analysis is similar for auditory hallucinations in subcortical regions. Among the whole population of older people, AS does not increase the risks for dementia, irrespective of Braak stage of NFT pathology. There was no evidence that the pattern of AS pathology in cortical areas was relevant to the risk of hallucination. In general, the hypothesis that AS as measured using these methods per se is a key determinant of cognitive clinical phenotypes is not supported.
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影响因子：
9.9
作者：
Olichney, JM;Galasko, D;Thal, LJ
通讯作者：
Thal, LJ
DOI：
10.1093/jnen/61.5.413
发表时间：
2002-05-01
影响因子：
3.2
作者：
Del Tredici, K;Rüb, U;Braak, H
通讯作者：
Braak, H
影响因子：
12.7
作者：
BRAAK, H;BRAAK, E;JELLINGER, K
通讯作者：
JELLINGER, K
影响因子：
9.9
作者：
Hurtig, HI;Trojanowski, JQ;Arnold, SE
通讯作者：
Arnold, SE
影响因子：
4.1
作者：
Horvath, Judit;Herrmann, Francois R.;Koevari, Enikoe
通讯作者：
Koevari, Enikoe