Borrego-Écija Sergi, Turon-Sans Janina, Ximelis Teresa, Aldecoa Iban, Molina-Porcel Laura, Povedano Mónica, Rubio Miguel Angel, Gámez Josep, Cano Antonio, Paré-Curell Martí, Bajo Lorena, Sotoca Javier, Clarimón Jordi, Balasa Mircea, Antonell Anna, Lladó Albert, Sánchez-Valle Raquel, Rojas-García Ricard, Gelpi Ellen
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
Neurology department, Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Brain Pathol. 2021 May;31(3):e12942. doi: 10.1111/bpa.12942. Epub 2021 Feb 12.
Cognitive impairment and behavioral changes in amyotrophic lateral sclerosis (ALS) are now recognized as part of the disease. Whether it is solely related to the extent of TDP-43 pathology is currently unclear. We aim to evaluate the influence of age, genetics, neuropathological features, and concomitant pathologies on cognitive impairment in ALS patients. We analyzed a postmortem series of 104 ALS patients and retrospectively reviewed clinical and neuropathological data. We assessed the burden and extent of concomitant pathologies, the role of APOE ε4 and mutations, and correlated these findings with cognitive status. We performed a logistic regression model to identify which pathologies are related to cognitive impairment. Cognitive decline was recorded in 38.5% of the subjects. Neuropathological features of frontotemporal lobar degeneration (FTLD) were found in 32.7%, explaining most, but not all, cases with cognitive impairment. Extent of TDP-43 pathology and the presence of hippocampal sclerosis were associated with cognitive impairment. Mutation carriers presented a higher burden of TDP-43 pathology and FTLD more frequently than sporadic cases. Most cases (89.4%) presented some degree of concomitant pathologies. The presence of concomitant pathologies was associated with older age at death. FTLD, but also Alzheimer's disease, were the predominant underlying pathologies explaining the cognitive impairment in ALS patients. In sum, FTLD explained the presence of cognitive decline in most but not all ALS cases, while other non-FTLD related findings can influence the cognitive status, particularly in older age groups.
肌萎缩侧索硬化症（ALS）中的认知障碍和行为改变现在被认为是该疾病的一部分。目前尚不清楚它是否仅与TDP - 43病理改变的程度有关。我们旨在评估年龄、遗传学、神经病理学特征和伴随病变对ALS患者认知障碍的影响。我们分析了104例ALS患者的尸检系列，并回顾性审查了临床和神经病理学数据。我们评估了伴随病变的负担和程度、APOE ε4和突变的作用，并将这些发现与认知状态相关联。我们进行了逻辑回归模型以确定哪些病变与认知障碍有关。38.5%的受试者记录有认知衰退。32.7%的患者发现有额颞叶变性（FTLD）的神经病理学特征，这解释了大多数但并非所有的认知障碍病例。TDP - 43病理改变的程度和海马硬化的存在与认知障碍相关。与散发病例相比，突变携带者TDP - 43病理改变和FTLD的负担更高且更常见。大多数病例（89.4%）存在某种程度的伴随病变。伴随病变的存在与死亡时年龄较大有关。FTLD以及阿尔茨海默病是解释ALS患者认知障碍的主要潜在病变。总之，FTLD解释了大多数但并非所有ALS病例中认知衰退的存在，而其他与FTLD无关的发现可影响认知状态，特别是在老年人群中。
