Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer’s disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese–American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia—broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with “frequent” neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aβ phase = 0 (lacking detectable Aβ plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer’s disease neuropathology.

边缘系统为主的年龄相关性 TDP-43 脑病神经病理学改变 (LATE-NC) 和阿尔茨海默病神经病理学改变 (ADNC) 均与老龄化人群的严重认知障碍有关。然而，LATE-NC 在所有 ADNC 中的流行率仍不确定。为了解决这一知识差距，神经病理学、遗传学和临床数据是从 13 项高质量的社区和人群纵向研究中汇编而成的。参与者来自美国（8 个队列，包括一个专注于日裔美国男性的队列）、英国（2 个队列）、巴西、奥地利和芬兰。参与者总人数为 6196 人，平均死亡年龄为 88.1 岁。并非每个人的所有数据都可用，并且研究设计中的队列和缺失数据量之间存在差异。在死前已知认知状态的人中（n  = 5665），43.0% 的人认知正常，14.9% 的人患有 MCI，42.4% 的人患有痴呆症——与该年龄组的流行病学数据大致一致。大约 99% 的参与者 ( n = 6125) 有可用的 CERAD 神经炎性淀粉样斑块评分数据。在这个子样本中，39.4% 的人有任何阶段的尸检确认的 LATE-NC。在“频繁”出现神经炎性淀粉样蛋白斑块的大脑中，54.9% 的人患有合并症 LATE-NC，而在未检测到神经炎性淀粉样蛋白斑块的大脑中，27.0% 的人患有 LATE-NC。可获得 3803 名参与者的 LATE-NC 分期数据，其中 25% 的 LATE-NC 分期 > 1（与认知障碍相关）。在 Thal Aβ 相 = 0（缺乏可检测的 Aβ 斑块）的个体子集中，具有 LATE-NC 的大脑具有相对更严重的原发性年龄相关性 tau 病 (PART)。共有 3267 名参与者拥有与额颞叶痴呆 (FTD) 相关的可用临床数据，没有人得到明确的 FTD 的临床诊断，也没有得到 TDP-43 包涵体（FTLD-TDP）的额颞叶变性的病理诊断。在 10 个具有接近死亡的详细神经认知评估的队列中，在整个 ADNC 严重程度范围内，LATE-NC 的认知往往更差。这项研究提供了对高龄 LATE-NC 当前患病率的可靠估计。LATE-NC 在近 40% 的参与者中被发现，并且经常但并非总是与阿尔茨海默病神经病理学共存。