Table_1_Amyloid-β, Tau, and Cognition in Cognitively Normal Older Individuals: Examining the Necessity to Adjust for Biomarker Status in Normative Data.DOCX

We investigated whether amyloid-β (Aβ) and tau affected cognition in cognitively normal (CN) individuals, and whether norms for neuropsychological tests based on biomarker-negative individuals would improve early detection of dementia. We included 907 CN individuals from 8 European cohorts and from the Alzheimer's disease Neuroimaging Initiative. All individuals were aged above 40, had Aβ status and neuropsychological data available. Linear mixed models were used to assess the associations of Aβ and tau with five neuropsychological tests assessing memory (immediate and delayed recall of Auditory Verbal Learning Test, AVLT), verbal fluency (Verbal Fluency Test, VFT), attention and executive functioning (Trail Making Test, TMT, part A and B). All test except the VFT were associated with Aβ status and this influence was augmented by age. We found no influence of tau on any of the cognitive tests. For the AVLT Immediate and Delayed recall and the TMT part A and B, we calculated norms in individuals without Aβ pathology (Aβ- norms), which we validated in an independent memory-clinic cohort by comparing their predictive accuracy to published norms. For memory tests, the Aβ- norms rightfully identified an additional group of individuals at risk of dementia. For non-memory test we found no difference. We confirmed the relationship between Aβ and cognition in cognitively normal individuals. The Aβ- norms for memory tests in combination with published norms improve prognostic accuracy of dementia.

本研究旨在探究β淀粉样蛋白（amyloid-β, Aβ）与tau蛋白（tau）对认知正常（cognitively normal, CN）个体认知功能的影响，同时验证基于生物标志物阴性人群的神经心理学测试常模能否提升痴呆的早期检出效能。本研究纳入了来自8个欧洲队列及阿尔茨海默病神经影像倡议（Alzheimer's disease Neuroimaging Initiative, ADNI）的907名认知正常个体，所有研究对象均年满40岁，且具备Aβ状态及神经心理学相关数据。本研究采用线性混合模型（Linear mixed models），分析Aβ与tau蛋白对5项神经心理学测试的影响，这些测试分别涵盖记忆功能（听觉词语学习测验（Auditory Verbal Learning Test, AVLT）的即刻回忆与延迟回忆）、词语流畅性（词语流畅性测验（Verbal Fluency Test, VFT））以及注意力与执行功能（连线测验（Trail Making Test, TMT）的A、B部分）。结果显示，除词语流畅性测验外，其余四项测试结果均与Aβ状态存在关联，且年龄会强化这一关联效应；本研究未发现tau蛋白对各项认知测试结果存在显著影响。针对听觉词语学习测验即刻回忆、延迟回忆以及连线测验A、B部分，我们在无Aβ病理改变的人群中计算了相应常模（以下简称Aβ阴性常模，Aβ- norms），并通过独立记忆门诊队列对该常模进行验证：将其预测效能与已发表的常模进行对比。针对记忆类测试，Aβ阴性常模可有效识别出额外的痴呆高危人群；而针对非记忆类测试，两种常模的预测效能无显著差异。本研究证实了认知正常个体中Aβ与认知功能的关联关系，且记忆类测试的Aβ阴性常模与已发表常模结合使用，可提升痴呆的预后预测效能。