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Criteria for the neuropathological diagnosis of dementing disorders: routes out of the swamp?

机译：神经病理学诊断的标准紊乱：从沼泽中排出的路线？

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Dementia, defined as deterioration in several cognitive domains, is an issue of enormous medical and socio-economic significance, poised to become a public health problem. Mental impairment and dementia are not only caused by neuronal cell death/loss, but predominantly by dysfunction and loss of synapses causing a default neuronal network. Consensus criteria for both the clinical and neuropathological diagnosis of different types of dementias have recently been updated. Clinical diagnostic accuracy using revised research criteria and newly developed biomarkers (MRI, PET, CSF analysis, genetic markers) ranges from 65 to 96% (for Alzheimer disease), with a diagnostic specificity versus other dementias of 23-88%. Neuropathological assessment of dementing disorders using immunohistochemistry, molecular biologic and genetic methods can achieve a diagnosis/classification, based on homogeneous definitions, harmonized inter-laboratory methods and standards for the assessment of nervous system lesions, in almost 99%, without, however, being able to clarify the causes or aetiology of most of these diseases. Since there is considerable clinical, genetic, morphological and molecular biological overlap between many disorders associated with cognitive impairment, in particular neurodegenerative proteinopathies, the reliability and clinical relevance of neuropathological criteria need better qualification and validation in order to increase the accuracy and reproducability of the diagnosis in these disorders. Although most of neurodegenerative dementing disorders are incurable at present, further prospective and concerted clinico-pathological studies using revised methodological and validated protocols are required to establish the nature, pattern and grade of lesions and thus to overcome the limitations of the current diagnostic framework. Data fusion may allow their uniform application and correlation with clinical data in order to approach a diagnostic "gold standard", and to create generally accepted criteria for differentiating cognitive disorders from healthy brain aging. Detection of disease-specific pathologies will be indispensable to determinate the efficacy of new therapy options.
机译：痴呆症，被定义为几个认知域的恶化，是一个巨大的医疗和社会经济意义的问题，准备成为一个公共卫生问题。精神损伤和痴呆不仅是由神经元细胞死亡/损失引起的，而且主要是通过功能障碍和突触损失导致默认神经元网络。最近更新了不同类型痴呆症的临床和神经病理学诊断的共识标准。使用修订的研究标准和新开发的生物标志物（MRI，PET，CSF分析，遗传标记）的临床诊断准确性范围为65％至96％（对于阿尔茨海默病），诊断特异性与其他23-88％的痴呆症相比。使用免疫组织化学的乳剂病毒紊乱的神经病理学评估，分子生物和遗传方法可以基于均匀定义，统一的实验室方法和评估神经系统病变评估的诊断/分类，但近99％，但没有能够澄清大多数这些疾病的原因或病症。由于与认知障碍相关的许多疾病之间存在相当大的临床，遗传，形态和分子生物学重叠，特别是神经退行性蛋白质化，神经病理学标准的可靠性和临床相关性需要更好的资格和验证，以提高诊断的准确性和再现性在这些疾病中。尽管目前大多数神经变性乳剂紊乱是可抵抗的，但需要使用修订的方法和验证的方案的进一步前瞻性和协调的临床病理学研究来建立病变的性质，模式和等级，从而克服目前诊断框架的局限性。数据融合可以允许其均匀的应用和与临床数据的相关性，以便接近诊断“黄金标准”，并创建普遍接受的标准，用于区分与健康脑老化的认知障碍。检测疾病特异性病理学将是必不可少的，以确定新疗法选择的功效。

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