Supplementary Material for: Clinicopathological Correlations and Concomitant Pathologies in Rapidly Progressive Dementia: A Brain Bank Series

<br><strong><em>Background:</em></strong> Rapidly progressive dementia (RPD) is caused by a heterogeneous group of both neurodegenerative and non-neurodegenerative disorders. The presence of concomitant pathologies, mainly Alzheimer's disease (AD), may act as a confounding variable in the diagnostic process of this group of diseases. <b><i>Objectives:</i></b> We aimed to describe clinicopathological features, including Alzheimer's co-pathology, and diagnostic accuracy in a postmortem series of RPD. <b><i>Methods:</i></b> Retrospective analysis of 160 brain donors with RPD (defined as 2 years of disease duration from the first symptom to death) registered at the Neurological Tissue Bank of the Biobanc-Hospital Clínic-IDIBAPS, from 2001 to 2011. <b><i>Results:</i></b> Prion diseases were the most frequent neuropathological diagnosis (67%), followed by non-prion neurodegenerative pathologies (17%), mostly AD and dementia with Lewy bodies, and non-neurodegenerative diseases (16%). We observed clinicopathological diagnostic agreement in 94% of the patients with prion RPD but only in 21% of those with non-prion RPD. Four patients with potentially treatable disorders were diagnosed, while still alive, as having Creutzfeldt-Jakob disease. Concomitant pathologies were detected in 117 (73%). Among all RPD cases, 51 presented moderate or frequent mature β-amyloid plaques (neuritic plaques), which are considered to be associated with positive amyloid biomarkers in vivo. <b><i>Conclusions:</i></b> Prion diseases were accurately identified in our series. In contrast, non-prion RPD diagnosis was poor while the patients were still alive, supporting the need for better diagnostic tools and confirmatory neuropathological studies. The presence of concomitant AD pathology in RPD should be taken into account in the interpretation of amyloid biomarkers.

**背景**：快速进展性痴呆（Rapidly progressive dementia, RPD）是一组异质性疾病导致的临床综合征，涵盖神经退行性与非神经退行性两类病因。伴随性病理改变（以阿尔茨海默病（Alzheimer's disease, AD）为主）可能成为该类疾病诊断过程中的混杂变量。**研究目标**：本研究旨在描述一系列尸检队列中快速进展性痴呆患者的临床病理特征（含阿尔茨海默病共病病理），并评估其诊断准确性。**研究方法**：对2001年至2011年期间，在Biobanc-Hospital Clínic-IDIBAPS神经组织库登记的160例RPD脑供者进行回顾性分析。本研究中RPD的定义为：从首发症状出现至患者死亡的病程时长为2年。**研究结果**：朊蛋白病是本队列中最常见的神经病理诊断（占比67%），其次为非朊蛋白神经退行性病变（占比17%，主要为阿尔茨海默病与路易体痴呆）以及非神经退行性疾病（占比16%）。本研究观察到，朊蛋白相关RPD患者的临床病理诊断符合率为94%，而非朊蛋白RPD患者的符合率仅为21%。有4例潜在可治疗的疾病患者在生前被误诊为克雅氏病（Creutzfeldt-Jakob disease, CJD）。共计117例（73%）患者检测到伴随性病理改变。在所有RPD病例中，51例出现中等量或多发成熟β-淀粉样蛋白斑块（神经炎性斑块），这类斑块被认为与体内淀粉样蛋白生物标志物阳性结果相关。**研究结论**：本研究队列中，朊蛋白病可被准确识别。与之形成对比的是，非朊蛋白RPD的生前诊断准确率较低，这提示亟需开发更精准的诊断工具并开展验证性神经病理学研究。在解读淀粉样蛋白生物标志物检测结果时，应充分考虑RPD患者伴随阿尔茨海默病病理改变的情况。