Data_Sheet_2_Validity Evidence for the Research Category, “Cognitively Unimpaired – Declining,” as a Risk Marker for Mild Cognitive Impairment and Alzheimer’s Disease.PDF

While clinically significant cognitive impairment is the key feature of the symptomatic stages of the Alzheimer’s disease (AD) continuum, subtle cognitive decline is now known to occur years before a clinical diagnosis of mild cognitive impairment (MCI) or dementia due to AD is made. The primary aim of this study was to examine criterion validity evidence for an operational definition of “cognitively unimpaired-declining” (CU-D) in the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a longitudinal cohort study following cognition and risk factors from mid-life and on. Cognitive status was determined for each visit using a consensus review process that incorporated internal norms and published norms; a multi-disciplinary panel reviewed cases first to determine whether MCI or dementia was present, and subsequently whether CU-D was present, The CU-D group differed from CU-stable (CU-S) and MCI on concurrent measures of cognition, demonstrating concurrent validity. Participants who changed from CU-S to CU-D at the next study visit demonstrated greater declines than those who stayed CU-S. In addition, those who were CU-D were more likely to progress to MCI or dementia than those who were CU-S (predictive validity). In a subsample with positron emission tomography (PET) imaging, the CU-D group also differed from the CU-S and MCI/Dementia groups on measures of amyloid and tau burden, indicating that biomarker evidence of AD was elevated in those showing sub-clinical (CU-D) decline. Together, the results corroborate other studies showing that cognitive decline begins long before a dementia diagnosis and indicate that operational criteria can detect subclinical decline that may signal AD or other dementia risk.

虽然临床显著的认知障碍是阿尔茨海默病（AD）病程中症候阶段的标志性特征，但现已明确，在作出轻度认知障碍（MCI）或由AD引起的痴呆的临床诊断之前，认知的微妙衰退已经发生数年。本研究的主要目的是检验威斯康星州阿尔茨海默病预防登记处（WRAP）中“认知未受损害但呈衰退趋势”（CU-D）操作定义的准则有效性证据。WRAP是一项纵向队列研究，从中年时期开始追踪认知状况和风险因素。每次访问时，通过结合内部规范和已发表规范的一致性审查过程确定认知状况；多学科评审小组首先审查病例，以确定是否存在MCI或痴呆，随后是否存在CU-D。CU-D组在认知的同期测量上与CU稳定（CU-S）和MCI组存在差异，显示出同期效度。在下次研究访问时，从CU-S转变为CU-D的参与者显示出比保持CU-S的参与者更大的衰退。此外，CU-D组比CU-S组更有可能进展为MCI或痴呆（预测效度）。在具有正电子发射断层扫描（PET）成像的子样本中，CU-D组在淀粉样物质和tau蛋白负荷的测量上与CU-S组和MCI/痴呆组也存在差异，表明AD的生物标志物证据在这些表现出亚临床（CU-D）衰退的个体中升高。综合这些结果，与其他研究表明认知衰退始于痴呆诊断之前的研究结果相一致，并表明操作标准可以检测出可能预示AD或其他痴呆风险的亚临床衰退。