Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is most often seen in the oldest-old (≥ 90 years of age) but can also be present in the younger-old (< 90 years of age). In this study, we compared the neuropathological associations of LATE-NC and contribution of LATE-NC to cognitive impairment between the oldest-old and younger-old. We observed significant differences in the prevalence of LATE-NC and its association with other co-pathologies in these two age groups. LATE-NC was present in 30.9% (34/110) of the oldest-old but only 9.4% (19/203) of the younger-old. Participants of the oldest-old with LATE-NC were more likely to have hippocampal sclerosis (HS) (55.9% vs. 10.5%, p < 0.001) and moderate to severe arteriolosclerosis (82.4% vs. 50%, p = 0.007), but not intermediate to high Alzheimer’s disease neuropathologic change (ADNC) (70.6% vs. 59.2%, p = 0.486) or Lewy body disease (LBD) (20.6% vs. 26.3%, p = 0.793). Participants of the younger-old with LATE-NC were more likely to have intermediate to high ADNC (94.7% vs. 55.4%, p < 0.001) and LBD (63.2% vs. 28.8%, p = 0.013) in addition to hippocampal sclerosis (42.1% vs. 6.5%, p < 0.001), and moderate to severe arteriolosclerosis (42.1% vs. 15.2%, p = 0.020). Of note, participants with LATE-NC and no to low ADNC were very rare in the younger-old (< 1%) but relatively common in the oldest-old (9.1%). Logistic regression modeling showed that in the oldest-old, both intermediate to high ADNC and LATE-NC were independently associated with higher odds of having dementia (OR: 5.09, 95% CI [1.99, 13.06], p < 0.001 for ADNC; OR: 3.28, 95% CI [1.25, 8.57], p = 0.015 for LATE-NC). In the younger-old, by contrast, intermediate to high ADNC and LBD were independently associated with higher odds of having dementia (OR: 4.43, 95% CI [2.27, 8.63], p < 0.001 for ADNC; OR: 2.55, 95% CI [1.21, 5.35], p < 0.014 for LBD), whereas LATE-NC did not show an independent association with dementia. Overall, LATE-NC is strongly associated with arteriolosclerosis and HS in both groups; however, in the younger-old, LATE-NC is associated with other neurodegenerative pathologies, such as ADNC and LBD; whereas in the oldest-old, LATE-NC can exist independent of significant ADNC.

边缘系统主导的年龄相关 TDP-43 脑病神经病理学改变 (LATE-NC) 最常见于老年人（≥ 90 岁），但也可能出现在较年轻的老年人（< 90 岁）中。在这项研究中，我们比较了 LATE-NC 的神经病理学关联以及 LATE-NC 对最年长老年人和较年轻老年人认知障碍的贡献。我们观察到这两个年龄组中 LATE-NC 的患病率及其与其他并发症的关联存在显着差异。LATE-NC 存在于 30.9% (34/110) 的最年长老年人中，但仅 9.4% (19/203) 存在于较年轻的老年人中。患有 LATE-NC 的年龄最大的参与者更有可能患有海马硬化 (HS)（55.9% vs. 10.5%，p  < 0.001）和中度至重度动脉硬化（82.4% vs. 50%，p = 0.007），但不是中度至高度阿尔茨海默病神经病理改变（ADNC）（70.6% vs. 59.2%，p  = 0.486）或路易体病（LBD）（20.6% vs. 26.3%，p  = 0.793）。 除了海马硬化之外，患有 LATE-NC 的年轻老年人参与者更有可能患有中度至高度 ADNC（94.7% vs. 55.4%，p < 0.001  ）和 LBD（63.2% vs. 28.8%，p = 0.013） （42.1% vs. 6.5%，p  < 0.001），以及中度至重度动脉硬化（42.1% vs. 15.2%，p = 0.020）。值得注意的是，患有 LATE-NC 和无或低 ADNC 的参与者在较年轻的老年人中非常罕见 (< 1%)，但在最年长的老年人中相对常见 (9.1%)。Logistic 回归模型显示，在最年长的老年人中，中度至高度 ADNC 和 LATE-NC 均与患痴呆症的较高几率独立相关（OR：5.09，95% CI [1.99，13.06]，ADNC 的 p < 0.001   ；OR：3.28，95% CI [1.25，8.57]， 对于 LATE-NC， p  = 0.015）。相比之下，在较年轻的老年人中，中度至高度 ADNC 和 LBD 与患痴呆症的较高几率独立相关（OR：4.43，95% CI [2.27，8.63]，ADNC p < 0.001；OR：  2.55，95  % CI [1.21，5.35]，  p LBD < 0.014），而 LATE-NC 并未显示出与痴呆的独立关联。总体而言，LATE-NC 与两组中的动脉硬化和 HS 密切相关；然而，在较年轻的老年人中，LATE-NC 与其他神经退行性疾病相关，例如 ADNC 和 LBD；而在最古老的情况下，LATE-NC 可以独立于显着的 ADNC 存在。