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

机译：痴呆症的神经病理学诊断标准：走出沼泽？ *）

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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：痴呆症定义为多个认知领域的恶化，是一个具有重大医学和社会经济意义的问题，有望成为公共卫生问题。精神损害和痴呆不仅是由神经元细胞的死亡/丢失引起的，而且主要是由功能障碍和突触丧失导致的神经元网络默认所致。最近已更新了不同类型痴呆的临床和神经病理学诊断的共识标准。使用修订后的研究标准和新开发的生物标志物（MRI，PET，CSF分析，遗传标志物）的临床诊断准确性范围为65％至96％（对于阿尔茨海默氏病），相对于其他痴呆症的诊断特异性为23-88％。使用免疫组织化学，分子生物学和遗传学方法对痴呆症进行神经病理学评估可以基于均一的定义，统一的实验室间方法和评估神经系统病变的标准，实现诊断/分类，几乎达到了99％，而没有能够弄清大多数这些疾病的病因或病因。由于与认知障碍相关的许多疾病（尤其是神经退行性蛋白病）之间在临床，遗传，形态和分子生物学方面存在大量重叠，因此神经病理学标准的可靠性和临床相关性需要更好的鉴定和验证，以提高诊断的准确性和可重复性在这些疾病中。尽管目前大多数神经退行性痴呆症是无法治愈的，但仍需要使用修订后的方法学和经过验证的方案进行进一步的前瞻性和一致的临床病理研究，以建立病变的性质，模式和等级，从而克服当前诊断框架的局限性。数据融合可以允许它们统一应用并与临床数据相关联，以达到诊断“金标准”，并创建公认的标准来区分认知障碍和健康的大脑衰老。疾病特异性病理的检测对于确定新疗法的有效性必不可少。

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