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Aging Neurosci."],"abstract":"<jats:p>While clinically significant cognitive impairment is the key feature of the symptomatic stages of the Alzheimer\u2019s 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 \u201ccognitively unimpaired-declining\u201d (CU-D) in the Wisconsin Registry for Alzheimer\u2019s 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.<\/jats:p>","DOI":"10.3389\/fnagi.2021.688478","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T06:16:31Z","timestamp":1627280191000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":54,"title":["Validity Evidence for the Research Category, \u201cCognitively Unimpaired \u2013 Declining,\u201d as a Risk Marker for Mild Cognitive Impairment and Alzheimer\u2019s Disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Rebecca","family":"Langhough Koscik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce P.","family":"Hermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Allison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay R.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin M.","family":"Jonaitis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly D.","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobey J.","family":"Betthauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T.","family":"Christian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianlian","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozioma","family":"Okonkwo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Birdsill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carey","family":"Gleason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sterling C.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.1212\/WNL.0000000000004015","article-title":"Effects of MCI subtype and reversion on progression to dementia in a community sample.","volume":"88","author":"Aerts","year":"2017","journal-title":"Neurology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.jalz.2010.03.006","article-title":"Clinical core of the Alzheimer\u2019s disease neuroimaging initiative: progress and plans.","volume":"6","author":"Aisen","year":"2010","journal-title":"Alzheimers Dement."},{"key":"B3","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","article-title":"The diagnosis of mild cognitive impairment due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease.","volume":"7","author":"Albert","year":"2011","journal-title":"Alzheimers Dement."},{"key":"B4","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1002\/ana.21509","article-title":"Prodromal Alzheimer\u2019s disease: successive emergence of the clinical symptoms.","volume":"64","author":"Amieva","year":"2008","journal-title":"Ann. 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