淀粉样蛋白-β 阳性预测认知能力下降，但认知能力预测向淀粉样蛋白-β 阳性进展。
Amyloid-β Positivity Predicts Cognitive Decline but Cognition Predicts Progression to Amyloid-β Positivity.
机构信息
Department of Psychiatry, University of California, San Diego, California; Center for Behavior Genetics of Aging, University of California, San Diego, California.
Department of Psychiatry, University of California, San Diego, California; Center for Behavior Genetics of Aging, University of California, San Diego, California.
出版信息
Biol Psychiatry. 2020 May 1;87(9):819-828. doi: 10.1016/j.biopsych.2019.12.021. Epub 2020 Jan 7.
BACKGROUND
Stage 1 of the National Institute on Aging-Alzheimer's Association's proposed Alzheimer's disease continuum is defined as amyloid-β (Aβ) positive but cognitively normal. Identifying at-risk individuals before Aβ reaches pathological levels could have great benefits for early intervention. Although Aβ levels become abnormal long before severe cognitive impairments appear, increasing evidence suggests that subtle cognitive changes may begin early, potentially before Aβ surpasses the threshold for abnormality. We examined whether baseline cognitive performance would predict progression from normal to abnormal levels of Aβ.
METHODS
We examined the association of baseline cognitive composites (Preclinical Alzheimer Cognitive Composite, Alzheimer's Disease Neuroimaging Initiative (ADNI) memory factor composite) with progression to Aβ positivity in 292 nondemented, Aβ-negative ADNI participants. Additional analyses included continuous cerebrospinal fluid biomarker levels to examine the effects of subthreshold pathology.
RESULTS
Forty participants progressed to Aβ positivity during follow-up. Poorer baseline performance on both cognitive measures was significantly associated with increased odds of progression. More abnormal levels of baseline cerebrospinal fluid phosphorylated tau and subthreshold Aβ were associated with increased odds of progression to Aβ positivity. Nevertheless, baseline ADNI memory factor composite performance predicted progression even after controlling for baseline biomarker levels and APOE genotype (Preclinical Alzheimer Cognitive Composite was trend level). Survival analyses were largely consistent: controlling for baseline biomarker levels, baseline Preclinical Alzheimer Cognitive Composite still significantly predicted progression time to Aβ positivity (ADNI memory factor composite was trend level).
CONCLUSIONS
The possibility of intervening before Aβ reaches pathological levels is of obvious benefit. Low-cost, noninvasive cognitive measures can be informative for determining who is likely to progress to Aβ positivity, even after accounting for baseline subthreshold biomarker levels.
背景
美国国家老龄化研究所-阿尔茨海默病协会提出的阿尔茨海默病连续体的第 1 阶段被定义为淀粉样蛋白-β（Aβ）阳性但认知正常。在 Aβ达到病理水平之前识别处于危险中的个体可能对早期干预有很大的好处。尽管 Aβ水平在严重认知障碍出现之前就已经异常升高，但越来越多的证据表明，细微的认知变化可能很早就开始出现，可能在 Aβ超过异常阈值之前。我们研究了基线认知表现是否可以预测从 Aβ正常水平进展到异常水平。
方法
我们研究了基线认知综合指标（临床前阿尔茨海默认知综合指标、阿尔茨海默病神经影像学倡议（ADNI）记忆因子综合指标）与 292 名无痴呆、Aβ阴性 ADNI 参与者从正常进展为 Aβ阳性的相关性。其他分析包括连续脑脊液生物标志物水平，以检查亚阈值病理学的影响。
结果
40 名参与者在随访期间进展为 Aβ阳性。两种认知测量的基线表现越差，进展的几率就越高。基线脑脊液磷酸化 tau 和亚阈值 Aβ的水平越异常，进展为 Aβ阳性的几率就越高。然而，即使在控制基线生物标志物水平和 APOE 基因型后（ADNI 记忆因子综合指标为趋势水平），基线 ADNI 记忆因子综合指标的表现仍能预测进展为 Aβ阳性的时间。生存分析基本一致：控制基线生物标志物水平后，基线临床前阿尔茨海默认知综合指标仍然显著预测进展为 Aβ阳性的时间（ADNI 记忆因子综合指标为趋势水平）。
结论
在 Aβ达到病理水平之前进行干预的可能性具有明显的益处。即使在考虑到基线亚阈值生物标志物水平的情况下，低成本、非侵入性的认知测量也可以为确定谁可能进展为 Aβ阳性提供信息。
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