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

Abstract

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.

Cross-sectional associations of CSF tau levels with Rey’s AVLT: A recency ratio study.

“…First, an algorithm that identifies cases where impairment may exist is applied, based on whether or not they meet one or more of the following criteria: (a) the participant performs 1.5 SD s below the mean on factor scores or individual measures of memory, executive function, language, working memory, or attention (Clark et al, 2016; Koscik et al, 2014; Langhough Koscik et al, 2021); (b) cognitive performance on one or more tests falls below values used in other studies as cut points for clinical MCI diagnoses (e.g., Wechsler Memory Scale-Revised [WMS-R] Logical Memory II, Wechsler, 1987: Story A score <9: AD Neuroimaging Initiative, Petersen et al, 2010); or (c) an abnormal informant report indicates subjective cognitive or functional decline. Second, a consensus diagnosis is determined by a team including physicians, clinical neuropsychologists, and clinical nurse practitioners, based on cognitive, medical history, lifestyle, subjective cognitive complaints, and informant data, for each visit (Langhough Koscik et al, 2021). The CUD label is assigned when participants are performing lower than expected on internal norms, and the consensus review team has ruled out other causes, including worse diagnoses such as MCI or dementia.…”

Item-Level Story Recall Predictors of Amyloid-Beta in Late Middle-Aged Adults at Increased Risk for Alzheimer’s Disease

“…An algorithm was created according to the robust norms to “flag” participants who are declining outside the range of the internal norms (1.5 SDs below the robust normative means). The flagged participants’ cognitive test performance, medical history, subjective and informant appraisals of memory, and medical examinations are reviewed and one of four determinations of cognitive status are made, based on NI Aβ-AA criteria ( Albert et al, 2011 ; McKhann et al, 2011 ; Jack et al, 2018 ): “cognitively unimpaired—stable,” “cognitively unimpaired—declining,” “MCI,” “Impaired not MCI,” or “dementia.” Further details regarding these approaches are detailed elsewhere ( Koscik et al, 2014 , 2019 ; Clark et al, 2016 ; Jonaitis et al, 2019 ; Langhough Koscik et al, 2021 ).…”

Spatio-Semantic Graphs From Picture Description: Applications to Detection of Cognitive Impairment

“…All data used in this study were transcripts from the first available audio recordings of The Cookie Theft picture description task only. Control data from DB ( n = 99 participants) were combined with Cognitively Unimpaired-Stable participant data from WRAP [ n = 836; ( 21 )]; participants with AD from DB ( n = 193) were combined with MCI participants from WRAP ( n = 26). The combined dataset includes four possible diagnoses: Cognitively Unimpaired-Stable (CUS) (935), Cognitively Unimpaired-Declining (CUD) (181 from WRAP), Impaired but not MCI (14 from WRAP), and MCI/Dementia (219).…”