From the Helen Wills Neuroscience Institute (T.G., S.M.L., W.J.J.), University of California; and Molecular Biophysics and Integrated Bioimaging (T.G., S.M.L., W.J.J.), Lawrence Berkeley National Laboratory, CA.
Neurology. 2020 Apr 7;94(14):e1512-e1524. doi: 10.1212/WNL.0000000000009216. Epub 2020 Mar 18.
To examine the feasibility of using cross-sectional PET to identify cognitive decliners among β-amyloid (Aβ)-negative cognitively normal (CN) elderly adults.
We determined the highest Aβ-affected region by ranking baseline and accumulation rates of florbetapir-PET regions in 355 CN elderly adults using F-florbetapir-PET from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The banks of the superior temporal sulcus (BANKSSTS) were found as the highest Aβ-affected region, and Aβ positivity in this region was defined as above the lowest boundary of BANKSSTS standardized uptake value ratio of Aβ+ (ADNI-defined COMPOSITE region) CN individuals. The entire CN cohort was divided as follows: stage 0, BANKSSTS-COMPOSITE-; stage 1, BANKSSTS+COMPOSITE-; and stage 2, BANKSSTS+COMPOSITE+. Linear mixed-effect (LME) models investigated subsequent longitudinal cognitive change, and F-flortaucipir (FTP)-PET was measured 4.8 ± 1.6 years later to track tau deposition.
LME analysis revealed that individuals in stage 1 (n = 64) and stage 2 (n = 99) showed 2.5 ( < 0.05) and 4.8 ( < 0.001) times faster memory decline, respectively, than those in stage 0 (n = 191) over >4 years of mean follow-up. Compared to stage 0, both stage 1 ( < 0.05) and stage 2 ( < 0.001) predicted higher FTP in entorhinal cortex.
Nominally Aβ- CN individuals with high Aβ in BANKSSTS are at increased risk of cognitive decline, probably showing an earlier stage of Aβ deposition. Our findings may help elucidate the association between brain Aβ accumulation and cognition in Aβ- CN cohorts.
This study provides Class II evidence that in elderly CN individuals those with high PET-identified superior temporal sulcus Aβ burden have an increased risk of cognitive decline.
探讨使用横断面 PET 识别β-淀粉样蛋白（Aβ）阴性认知正常（CN）老年人认知下降者的可行性。
我们使用来自阿尔茨海默病神经影像学倡议（ADNI）的 F-氟比他哌-PET 确定了 355 名 CN 老年人基线和 Aβ-PET 区域积累率最高的 Aβ 受影响区域。在该区域发现了颞上沟（BANKSSTS）的银行，该区域被定义为高于 BANKSSTS 标准化摄取比值 Aβ+（ADNI 定义的复合区域）CN 个体的最低边界。整个 CN 队列分为以下阶段：0 期，BANKSSTS-COMPOSITE-；1 期，BANKSSTS+COMPOSITE-；2 期，BANKSSTS+COMPOSITE+。线性混合效应（LME）模型研究了随后的纵向认知变化，并在 4.8±1.6 年后测量了 F-氟托西匹尔（FTP）-PET 以追踪 tau 沉积。
LME 分析显示，1 期（n=64）和 2 期（n=99）个体在 4 年以上的平均随访中，记忆下降速度分别比 0 期（n=191）快 2.5（<0.05）和 4.8（<0.001）倍。与 0 期相比，1 期（<0.05）和 2 期（<0.001）均预测了内嗅皮层中更高的 FTP。
名义上 Aβ-CN 个体在 BANKSSTS 中具有高 Aβ，其认知下降的风险增加，可能表现出 Aβ 沉积的更早阶段。我们的研究结果可能有助于阐明 Aβ-CN 队列中脑 Aβ 积累与认知之间的关系。
本研究提供了 II 级证据，表明在老年 CN 个体中，具有高 PET 确定的颞上沟 Aβ 负担的个体认知下降风险增加。
