Department of Neurology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Neuroscience Centre, Samsung Medical Centre, Seoul, South Korea.
Eur J Neurol. 2024 Dec;31(12):e16482. doi: 10.1111/ene.16482. Epub 2024 Sep 14.
Amyloid β (Aβ), a major biomarker of Alzheimer's disease, leads to tau accumulation, neurodegeneration and cognitive decline. Modelling the trajectory of Aβ accumulation in cognitively unimpaired (CU) individuals is crucial, as treatments targeting Aβ are anticipated. The evolution of Aβ levels was investigated to determine whether it could lead to classification into different groups by studying longitudinal Aβ changes in older CU individuals, and differences between the groups were compared.
A total of 297 CU participants were included from the Alzheimer's Disease Neuroimaging Initiative database, and these participants underwent apolipoprotein E (APOE) genotyping, neuropsychological testing, brain magnetic resonance imaging, and an average of 3.03 follow-up F-florbetapir positron emission tomography scans. Distinct Aβ trajectory patterns were classified using latent class growth analysis, and longitudinal cognitive performances across these patterns were assessed with a linear mixed effects model.
The optimal model consisted of three classes, with a high entropy value of 0.947. The classes were designated as follows: class 1, non-accumulation group (n = 197); class 2, late accumulation group (n = 70); and class 3, early accumulation group (n = 30). The late accumulation and early accumulation groups had more APOE ε4 carriers than the non-accumulation group. The longitudinal analysis of cognitive performance revealed that the early accumulation group showed the steepest decline (modified Preclinical Alzheimer's Cognitive Composite with digit symbol substitution [mPACCdigit], p < 0.001; modified Preclinical Alzheimer's Cognitive Composite with trails B [mPACCtrailsB], p < 0.001) and the late accumulation group showed a steeper decline (mPACCdigit, p = 0.014; mPACCtrailsB, p = 0.007) compared to the non-accumulation group.
Our study showed the heterogeneity of Aβ accumulation trajectories in CU older individuals. The prognoses for cognitive decline differ according to the Aβ trajectory patterns.
淀粉样蛋白β（Aβ）是阿尔茨海默病的主要生物标志物，可导致tau 蛋白积累、神经退行性变和认知能力下降。对认知正常（CU）个体中 Aβ 积累的轨迹进行建模至关重要，因为预期会有针对 Aβ 的治疗方法。通过研究老年 CU 个体的纵向 Aβ 变化，研究 Aβ 水平的变化是否可以导致不同组别分类，并比较组间差异，以确定其是否可以导致分类。
从阿尔茨海默病神经影像学倡议数据库中纳入了 297 名 CU 参与者，这些参与者进行了载脂蛋白 E（APOE）基因分型、神经心理学测试、脑磁共振成像以及平均 3.03 次 F-氟比他滨正电子发射断层扫描（PET）随访。使用潜在类别增长分析对不同的 Aβ 轨迹模式进行分类，并使用线性混合效应模型评估这些模式的纵向认知表现。
最佳模型由三个类别组成，其熵值为 0.947。这些类别分别指定为：1 类，非积累组（n=197）；2 类，晚积累组（n=70）；3 类，早积累组（n=30）。晚积累组和早积累组的 APOE ε4 携带者比非积累组多。对认知表现的纵向分析表明，早积累组的下降最为明显（改良的临床前阿尔茨海默病认知复合量表与数字符号替换[mPACCdigit]，p<0.001；改良的临床前阿尔茨海默病认知复合量表与轨迹 B[mPACCtrailsB]，p<0.001），晚积累组的下降也较为明显（mPACCdigit，p=0.014；mPACCtrailsB，p=0.007），与非积累组相比。
我们的研究显示了 CU 老年个体中 Aβ 积累轨迹的异质性。根据 Aβ 轨迹模式，认知下降的预后不同。
