在记忆门诊人群中应用 ATN 方案：ABIDE 项目。

Applying the ATN scheme in a memory clinic population: The ABIDE project.

机构信息

From the Alzheimer Center Amsterdam, Department of Neurology (D.A., A.d.W., R.O., W.P., F.B., C.G., I.v.M., M.Z., B.N.v.B., P.S., W.M.v.d.F.), Department of Radiology & Nuclear Medicine (R.O., C.G., M.Y., F.B., B.N.v.B.), and Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology & Biostatistics (I.v.M., W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; Laboratory of Neuroimaging of Aging (LANVIE) (D.A., G.B.F.), University of Geneva, Switzerland; Memory Clinic (D.A.), University Hospitals of Geneva, Switzerland; Laboratory of Alzheimer's Neuroimaging and Epidemiology (LANE) (D.A.), Saint John of God Clinical Research Centre; Department of Molecular and Translational Medicine (D.A.), University of Brescia, Italy; Clinical Memory Research Unit (R.O.), Lund University, Malmö, Sweden; Institutes of Neurology and Healthcare Engineering (F.B.), UCL, London, UK; and Memory Clinic (D.A., G.B.F.), University Hospitals of Geneva, Switzerland.

出版信息

Neurology. 2019 Oct 22;93(17):e1635-e1646. doi: 10.1212/WNL.0000000000008361. Epub 2019 Oct 9.

DOI:10.1212/WNL.0000000000008361

PMID:31597710

Abstract

OBJECTIVE

To apply the ATN scheme to memory clinic patients, to assess whether it discriminates patient populations with specific features.

METHODS

We included 305 memory clinic patients (33% subjective cognitive decline [SCD]: 60 ± 9 years, 61% M; 19% mild cognitive impairment [MCI]: 68 ± 9 years, 68% M; 48% dementia: 66 ± 10 years, 58% M) classified for positivity (±) of amyloid (A) ([F]Florbetaben PET), tau (T) (CSF p-tau), and neurodegeneration (N) (medial temporal lobe atrophy). We assessed ATN profiles' demographic, clinical, and cognitive features at baseline, and cognitive decline over time.

RESULTS

The proportion of A+T+N+ patients increased with syndrome severity (from 1% in SCD to 14% in MCI and 35% in dementia), while the opposite was true for A-T-N- (from 48% to 19% and 6%). Compared to A-T-N-, patients with the Alzheimer profiles (A+T+N- and A+T+N+) were older (both 0.05) and had a higher prevalence of ε4 (both 0.05) and lower Mini-Mental State Examination (MMSE) (both 0.05), memory (both 0.05), and visuospatial abilities (both 0.05) at baseline. Non-Alzheimer profiles A-T-N+ and A-T+N+ showed more severe white matter hyperintensities (both 0.05) and worse language performance (both < 0.05) than A-T-N-. A linear mixed model showed faster decline on MMSE over time in A+T+N- and A+T+N+ ( = 0.059 and < 0.001 vs A-T-N-), attributable mainly to patients without dementia.

CONCLUSIONS

The ATN scheme identified different biomarker profiles with overlapping baseline features and patterns of cognitive decline. The large number of profiles, which may have different implications in patients with vs without dementia, poses a challenge to the application of the ATN scheme.

摘要

目的

将 ATN 方案应用于记忆诊所患者，评估其是否能区分具有特定特征的患者人群。

方法

我们纳入了 305 名记忆诊所患者（33%的主观认知下降[SCD]：60±9 岁，61%为男性；19%的轻度认知障碍[MCI]：68±9 岁，68%为男性；48%的痴呆：66±10 岁，58%为男性），根据淀粉样蛋白（A）（[F]氟比他滨 PET）、tau（T）（CSF p-tau）和神经退行性变（N）（内侧颞叶萎缩）的阳性（+）情况进行分类。我们评估了 ATN 谱在基线时的人口统计学、临床和认知特征，并评估了随时间的认知下降。

结果

随着综合征严重程度的增加，A+T+N+患者的比例增加（从 SCD 的 1%增加到 MCI 的 14%和痴呆的 35%），而 A-T-N-（从 48%减少到 19%和 6%）则相反。与 A-T-N-相比，阿尔茨海默病谱（A+T+N-和 A+T+N+）患者年龄更大（均为 0.05），ε4 发生率更高（均为 0.05），简易精神状态检查（MMSE）评分更低（均为 0.05），记忆（均为 0.05）和视空间能力（均为 0.05）在基线时更低。非阿尔茨海默病谱 A-T-N+和 A-T+N+患者的脑白质高信号（均为 0.05）更严重，语言表现更差（均为 < 0.05）比 A-T-N-。线性混合模型显示，A+T+N-和 A+T+N+患者的 MMSE 评分随时间的下降速度更快（=0.059 和 < 0.001 与 A-T-N-相比），主要归因于没有痴呆的患者。