Difference in trajectories according to early amyloid accumulation in cognitively unimpaired elderly

IF 4.5 2区医学 Q1 CLINICAL NEUROLOGY

European Journal of Neurology Pub Date : 2024-09-14 DOI:10.1111/ene.16482

Young Ju Kim, Jihwan Yun, Sang Won Seo, Jun Pyo Kim, Hyemin Jang, Hee Jin Kim, Duk L. Na, Sookyoung Woo, Min Young Chun, for the Alzheimer's Disease Neuroimaging Initiative

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引用次数: 0

Abstract

Background and purpose

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.

Methods

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 ¹⁸F-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.

Results

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.

Conclusions

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.

Abstract Image

查看原文本刊更多论文

认知功能未受损的老年人早期淀粉样蛋白积累轨迹的差异。

背景和目的淀粉样蛋白 β（Aβ）是阿尔茨海默病的主要生物标志物，会导致 tau 积累、神经变性和认知能力下降。对认知功能未受损（CU）个体的 Aβ 积累轨迹进行建模至关重要，因为人们期待着针对 Aβ 的治疗方法。方法从阿尔茨海默病神经影像学倡议（Alzheimer's Disease Neuroimaging Initiative）数据库中纳入了297名CU参与者，这些参与者接受了载脂蛋白E（APOE）基因分型、神经心理学测试、脑磁共振成像和平均3.03次的随访18F-氟贝他匹正电子发射断层扫描。利用潜类增长分析对不同的 Aβ 轨迹模式进行了分类，并利用线性混合效应模型对这些模式的纵向认知表现进行了评估。这三个等级分别是：第 1 级，非积累组（n = 197）；第 2 级，晚期积累组（n = 70）；第 3 级，早期积累组（n = 30）。晚期积累组和早期积累组比非积累组有更多的 APOE ε4携带者。认知能力的纵向分析表明，早期积累组的认知能力下降幅度最大（改良的临床前阿尔茨海默氏症认知综合能力与数字符号替换[mPACCdigit]，p < 0.001；改良的临床前阿尔茨海默氏症认知综合能力与轨迹 B [mPACCtrailsB]，p < 0.结论我们的研究显示了老年 CU 中 Aβ 累积轨迹的异质性。结论我们的研究表明，CU 老年人的 Aβ 累积轨迹具有异质性。

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来源期刊

European Journal of Neurology 医学-临床神经学

CiteScore

9.70

自引率

2.00%

发文量

418

审稿时长

1 months

期刊介绍： The European Journal of Neurology is the official journal of the European Academy of Neurology and covers all areas of clinical and basic research in neurology, including pre-clinical research of immediate translational value for new potential treatments. Emphasis is placed on major diseases of large clinical and socio-economic importance (dementia, stroke, epilepsy, headache, multiple sclerosis, movement disorders, and infectious diseases).