Identifying best methods for the detection of subtle cognitive decline

项目摘要/摘要 新提交的PAS-19-391(面向下一代研究人员的小型研究资助计划 AD/ADRD研究：重点领域归档和利用现有数据集进行分析[R03])。 最近的统计数据显示，如果2018年每个活着的人都会患上阿尔茨海默病(AD)，那么他们就会早早地 如果诊断准确，将节省7.9万亿美元的医疗和长期护理成本。虽然 阿尔茨海默病(AD)生物标志物的出现彻底改变了我们对AD发病机制的认识 在临床前阶段，这些方法通常是昂贵的、侵入性的、由于农村地区的原因而无法进入， 费用，或药物禁忌症。此外，除了关注AD生物标记物之外，还必须 强调认知障碍和随后的功能障碍是这种疾病的特征 对患者及其家人的生活产生负面影响。新出现的证据表明，微妙的认知 变化可能比最初在AD模型中描述的更早发生，以及这些微妙的认知变化 在预测进展为轻度认知障碍方面，增加有意义的预后价值，超过AD生物标志物 损害(MCI)和痴呆症。识别临床前期患者细微认知功能下降的金标准方法 然而，广告仍不清楚。因此，我们建议将四种不同的分类算法应用于微妙 开放源码的阿尔茨海默病神经成像倡议(ADNI)数据集的认知功能下降。四个 分类方法包括两种主观方法：自我报告主观认知减退(SELF-SCD) 和报案者报告的主观认知下降(INFORM-SCD)；和两种客观方法：敏感的 神经心理学基于个体测试的方法称为客观定义的细微认知下降(Obj-SCD) 以及一种基于综合分数的方法，使用临床前阿尔茨海默氏症认知复合体来识别细微的 认知功能下降(PACC-SCD)。该提案的具体目标包括：1)比较4个AD生物标志物 微妙的认知衰退定义(自我-SCD、信息-SCD、对象-SCD和PACC-SCD)；2)决定 微妙认知下降的定义最好地捕捉了微妙认知下降前一年的客观认知下降 认知衰退分类；以及3)检查纵向a)临床和b)生物标记物进展 微妙的认知衰退定义，以确定具有最佳预测效用的定义。评选结果 拟议的目标可能会影响未来研究的设计，因为它简单、可靠、成本高- 缩小初始参与者池的有效方法，以便只有风险最高的参与者才需要进行PET 为筛查目的进行扫描将大大节省成本。此外，这些结果将作为 为未来的赠款申请提供关键的初步数据，并成为提高临床意义的关键一步 对那些未来有下降风险的人的早期检测方法，特别是那些获得AD生物标志物的有限的人 测试。

PROJECT SUMMARY / ABSTRACT New submission for PAS-19-391 (Small Research Grant Program for the Next Generation of Researchers in AD/ADRD Research: Area of Focus Archiving and Leveraging Existing Data Sets for Analyses [R03]). Recent statistics show that if everyone alive in 2018 who will develop Alzheimer’s disease (AD) had early and accurate diagnosis, there would be a savings of $7.9 trillion in medical and long-term care costs. Although the advent of Alzheimer’s disease (AD) biomarkers has revolutionized our understanding of AD pathogenesis during the preclinical phase, these approaches are often expensive, invasive, inaccessible due to rural location, cost, or medical contraindications. Additionally, beyond a focus on AD biomarkers alone, it is essential to emphasize that cognitive difficulties and subsequent functional impairment are the features of the disease that negatively impact the lives of patients and their families. Emerging evidence suggests that subtle cognitive changes may develop much earlier than originally described in models of AD and these subtle cognitive changes add meaningful prognostic value, above and beyond AD biomarkers, in predicting progression to mild cognitive impairment (MCI) and dementia. The gold standard approach for identifying subtle cognitive decline in preclinical AD, however, remains unclear. Therefore, we propose to apply four different classification algorithms for subtle cognitive decline in the open source Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. The four classifications methods include two subjective approaches: self-reported subjective cognitive decline (Self-SCD) and informant-reported subjective cognitive decline (Inform-SCD); and two objective approaches: a sensitive neuropsychological individual test-based approach called objectively-defined subtle cognitive decline (Obj-SCD) and a composite score-based approach using the preclinical Alzheimer’s cognitive composite to identify subtle cognitive decline (PACC-SCD). The specific aims of this proposal include: 1) Compare AD biomarkers across 4 subtle cognitive decline definitions (Self-SCD, Inform-SCD, Obj-SCD, and PACC-SCD); 2) Determine which subtle cognitive decline definitions best capture objective cognitive decline in the year preceding the subtle cognitive decline classification; and 3) Examine longitudinal a) clinical and b) biomarker progression across subtle cognitive decline definitions to determine the definitions with the best predictive utility. Results of the proposed aims will likely impact the design of future studies, as having simple, yet reliable, and highly cost- efficient methods for narrowing the initial pool of participants so that only those at greatest risk require a PET scan for screening purposes would result in significant cost-savings. Additionally, these results will serve as critical preliminary data for future grant applications, and be a key step toward improving clinically meaningful early detection methods of those at risk for future decline, particularly those with limited access to AD biomarker testing.