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.

中文翻译：

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Aβ 阳性预测认知能力下降，但认知预测 Aβ 阳性进展

背景 国家衰老研究所的第 1 阶段 - 阿尔茨海默氏症协会提出的阿尔茨海默病连续体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高危个体可能对早期干预有很大好处。尽管 Aβ 水平在严重认知障碍出现之前很久就变得异常，但越来越多的证据表明，细微的认知变化可能很早就开始了，可能在 Aβ 超过异常阈值之前。我们检查了基线认知表现是否会预测 Aβ 从正常水平到异常水平的进展。方法 我们检查了基线认知复合物（临床前阿尔茨海默病认知复合物，阿尔茨海默病 s 疾病神经影像学倡议 (ADNI) 记忆因子复合材料）在 292 名非痴呆、Aβ 阴性 ADNI 参与者中进展为 Aβ 阳性。其他分析包括连续的脑脊液生物标志物水平，以检查阈下病理的影响。结果 40 名参与者在随访期间进展为 Aβ 阳性。两种认知测量的较差基线表现与进展几率的增加显着相关。更多异常水平的基线脑脊液磷酸化 tau 和亚阈值 Aβ 与进展为 Aβ 阳性的几率增加有关。尽管如此，即使在控制基线生物标志物水平和 APOE 基因型（临床前阿尔茨海默认知复合物是趋势水平）之后，基线 ADNI 记忆因子复合性能仍能预测进展。生存分析基本一致：控制基线生物标志物水平，基线临床前阿尔茨海默认知复合物仍然显着预测 Aβ 阳性的进展时间（ADNI 记忆因子复合物是趋势水平）。结论 在 Aβ 达到病理水平之前进行干预的可能性是明显的。即使在考虑了基线亚阈值生物标志物水平之后，低成本、无创的认知措施也可以为确定谁可能进展为 Aβ 阳性提供信息。结论 在 Aβ 达到病理水平之前进行干预的可能性是明显的。即使在考虑了基线亚阈值生物标志物水平之后，低成本、无创的认知措施也可以为确定谁可能进展为 Aβ 阳性提供信息。结论 在 Aβ 达到病理水平之前进行干预的可能性是明显的。即使在考虑了基线亚阈值生物标志物水平之后，低成本、无创的认知措施也可以为确定谁可能进展为 Aβ 阳性提供信息。