From the Department of Epidemiology and Biostatistics (J.W.), University of California, San Francisco; Department of Epidemiology (J.W., S.A., M.M.G.), Boston University, MA; Department of Neurology (D.C.W., S.A.S., C.K., M.M.C.), University of California, Irvine; Imaging of Dementia and Aging Laboratory (C.S.D., E.F.F.), Department of Neurology, University of California, Davis; and Department of Epidemiology and Biostatistics (L.J., M.M.C.), and Department of Neurobiology and Behavior (C.K.), University of California, Irvine.
Neurology. 2024 Aug 13;103(3):e209665. doi: 10.1212/WNL.0000000000209665. Epub 2024 Jul 15.
Amyloid pathology, vascular disease pathology, and pathologies affecting the medial temporal lobe are associated with cognitive trajectories in older adults. However, only limited evidence exists on how these pathologies influence cognition in the oldest old. We evaluated whether amyloid burden, white matter hyperintensity (WMH) volume, and hippocampal volume (HV) are associated with cognitive level and decline in the oldest old.
This was a longitudinal, observational community-based cohort study. We included participants with F-florbetapir PET and MRI data from the 90+ Study. Amyloid load was measured using the standardized uptake value ratio in the precuneus/posterior cingulate with eroded white matter mask as reference. WMH volume was log-transformed. All imaging measures were standardized using sample means and SDs. HV and log-WMH volume were normalized by total intracranial volume using the residual approach. Global cognitive performance was measured by the Mini-Mental State Examination (MMSE) and modified MMSE (3MS) tests, repeated every 6 months. We used linear mixed-effects models with random intercepts; random slopes; and interaction between time, time squared, and imaging variables to estimate the associations of imaging variables with cognitive level and cognitive decline. Models were adjusted for demographics, APOE genotype, and health behaviors.
The sample included 192 participants. The mean age was 92.9 years, 125 (65.1%) were female, 71 (37.0%) achieved a degree beyond college, and the median follow-up time was 3.0 years. A higher amyloid load was associated with a lower cognitive level (β = -0.82, 95% CI -1.17 to -0.46; β = -2.77, 95% CI -3.69 to -1.84). A 1-SD decrease in HV was associated with a 0.70-point decrease in the MMSE score (95% CI -1.14 to -0.27) and a 2.27-point decrease in the 3MS score (95% CI -3.40 to -1.14). Clear nonlinear cognitive trajectories were detected. A higher amyloid burden and smaller HV were associated with faster cognitive decline. WMH volume was not significantly associated with cognitive level or decline.
Amyloid burden and hippocampal atrophy are associated with both cognitive level and cognitive decline in the oldest old. Our findings shed light on how different pathologies contributed to driving cognitive function in the oldest old.
淀粉样蛋白病理学、血管疾病病理学和影响内侧颞叶的病理学与老年人的认知轨迹有关。然而，关于这些病理学如何影响最年长老年人的认知，仅有有限的证据。我们评估了淀粉样蛋白负荷、脑白质高信号（WMH）体积和海马体积（HV）是否与认知水平和最年长老年人的认知下降有关。
这是一项纵向、观察性的社区为基础的队列研究。我们纳入了来自 90+ 研究的 F-氟脱氧葡萄糖 PET 和 MRI 数据的参与者。使用内侧楔前叶/后扣带回的标准化摄取比值来衡量淀粉样蛋白负荷，以侵蚀性白质掩模作为参考。WMH 体积取对数转换。所有影像学测量均使用样本均值和标准差进行标准化。使用残差方法，根据总颅内体积对 HV 和 log-WMH 体积进行归一化。使用简易精神状态检查（MMSE）和改良 MMSE（3MS）测试测量整体认知表现，每 6 个月重复一次。我们使用具有随机截距、随机斜率和时间、时间平方与影像学变量之间相互作用的线性混合效应模型来估计影像学变量与认知水平和认知下降的相关性。模型调整了人口统计学、APOE 基因型和健康行为因素。
样本包括 192 名参与者。平均年龄为 92.9 岁，125 名（65.1%）为女性，71 名（37.0%）拥有大学以上学历，中位随访时间为 3.0 年。较高的淀粉样蛋白负荷与认知水平较低有关（β=-0.82，95%置信区间-1.17 至-0.46；β=-2.77，95%置信区间-3.69 至-1.84）。HV 降低 1 个标准差与 MMSE 评分降低 0.70 分（95%置信区间-1.14 至-0.27）和 3MS 评分降低 2.27 分（95%置信区间-3.40 至-1.14）有关。检测到清晰的非线性认知轨迹。较高的淀粉样蛋白负荷和较小的 HV 与认知下降较快有关。WMH 体积与认知水平或下降无显著相关性。
淀粉样蛋白负荷和海马萎缩与最年长老年人的认知水平和认知下降均有关。我们的研究结果揭示了不同的病理学如何共同导致最年长老年人的认知功能下降。
