{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:30:17Z","timestamp":1793140217752,"version":"4.5.0"},"reference-count":43,"publisher":"Cambridge University Press (CUP)","issue":"5","license":[{"start":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T00:00:00Z","timestamp":1602547200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Int Neuropsychol Soc"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"S1355617720000934_as1\"><jats:title>Objective:<\/jats:title><jats:p>Alzheimer\u2019s disease (AD) studies are increasingly targeting earlier (pre)clinical populations, in which the expected degree of observable cognitive decline over a certain time interval is reduced as compared to the dementia stage. Consequently, endpoints to capture early cognitive changes require refinement. We aimed to determine the sensitivity to decline of widely applied neuropsychological tests at different clinical stages of AD as outlined in the National Institute on Aging \u2013 Alzheimer\u2019s Association (NIA-AA) research framework.<\/jats:p><\/jats:sec><jats:sec id=\"S1355617720000934_as2\"><jats:title>Method:<\/jats:title><jats:p>Amyloid-positive individuals (as determined by positron emission tomography or cerebrospinal fluid) with longitudinal neuropsychological assessments available were included from four well-defined study cohorts and subsequently classified among the NIA-AA stages. For each stage, we investigated the sensitivity to decline of 17 individual neuropsychological tests using linear mixed models.<\/jats:p><\/jats:sec><jats:sec id=\"S1355617720000934_as3\"><jats:title>Results:<\/jats:title><jats:p>1103 participants (age = 70.54 \u00b1 8.7, 47% female) were included: <jats:italic>n<\/jats:italic> = 120 Stage 1, <jats:italic>n<\/jats:italic> = 206 Stage 2, <jats:italic>n<\/jats:italic> = 467 Stage 3 and <jats:italic>n<\/jats:italic> = 309 Stage 4. Neuropsychological tests were differentially sensitive to decline across stages. For example, Category Fluency captured significant 1-year decline as early as Stage 1 (<jats:italic>\u03b2<\/jats:italic> = \u2212.58, <jats:italic>p<\/jats:italic> &lt; .001). Word List Delayed Recall (<jats:italic>\u03b2<\/jats:italic> = \u2212.22, <jats:italic>p<\/jats:italic> &lt; .05) and Trail Making Test (<jats:italic>\u03b2<\/jats:italic> = 6.2, <jats:italic>p<\/jats:italic> &lt; .05) became sensitive to 1-year decline in Stage 2, whereas the Mini-Mental State Examination did not capture 1-year decline until Stage 3 (<jats:italic>\u03b2<\/jats:italic> = \u22121.13, <jats:italic>p<\/jats:italic> &lt; .001) and 4 (<jats:italic>\u03b2<\/jats:italic> = \u22122.23, <jats:italic>p<\/jats:italic> &lt; .001).<\/jats:p><\/jats:sec><jats:sec id=\"S1355617720000934_as4\"><jats:title>Conclusions:<\/jats:title><jats:p>We demonstrated that commonly used neuropsychological tests differ in their ability to capture decline depending on clinical stage within the AD continuum (preclinical to dementia). This implies that stage-specific cognitive endpoints are needed to accurately assess disease progression and increase the chance of successful treatment evaluation in AD.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s1355617720000934","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T06:30:31Z","timestamp":1602570631000},"page":"426-438","source":"Crossref","is-referenced-by-count":65,"title":["Identifying Sensitive Measures of Cognitive Decline at Different Clinical Stages of Alzheimer\u2019s Disease"],"prefix":"10.1017","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3712-4790","authenticated-orcid":false,"given":"Roos J.","family":"Jutten","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sietske A.M.","family":"Sikkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca E.","family":"Amariglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel F.","family":"Buckley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Properzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gad A.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorene M.","family":"Rentz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Teunissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart N.M.","family":"Van Berckel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiesje M.","family":"Van der Flier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Scheltens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reisa A.","family":"Sperling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn V.","family":"Papp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"National Alzheimer\u2019s Coordinating Center, the Harvard Aging Brain Study, and the Alzheimer Dementia Cohort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2020,10,13]]},"reference":[{"key":"S1355617720000934_ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.06.2365"},{"key":"S1355617720000934_ref34","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2017.281055"},{"key":"S1355617720000934_ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2010.03.006"},{"key":"S1355617720000934_ref23","first-page":"19","article-title":"Sensitivity of composite scores to amyloid burden in preclinical Alzheimer\u2019s disease: Introducing the Z-scores of attention, verbal fluency, and episodic memory for nondemented older adults composite score","volume":"2","author":"Lim","year":"2016","journal-title":"Alzheimer\u2019s and Dementia"},{"key":"S1355617720000934_ref17","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.140.6.566"},{"key":"S1355617720000934_ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"S1355617720000934_ref11","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-018-0381-0"},{"key":"S1355617720000934_ref37","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170850"},{"key":"S1355617720000934_ref5","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-016-0176-z"},{"key":"S1355617720000934_ref3","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e318142774e"},{"key":"S1355617720000934_ref30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.07.154"},{"key":"S1355617720000934_ref39","volume-title":"WMS-R: Wechsler Memory Scale-Revised","author":"Wechsler","year":"1987"},{"key":"S1355617720000934_ref8","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.803"},{"key":"S1355617720000934_ref42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2012.01.005"},{"key":"S1355617720000934_ref22","volume-title":"Neuropsychological Assessment","author":"Lezak","year":"2004"},{"key":"S1355617720000934_ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"S1355617720000934_ref32","volume-title":"Rey Auditory Verbal Learning Test: A Handbook","author":"Schmidt","year":"1996"},{"key":"S1355617720000934_ref6","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.2008"},{"key":"S1355617720000934_ref24","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000431"},{"key":"S1355617720000934_ref12","doi-asserted-by":"publisher","DOI":"10.1037\/0894-4105.22.4.531"},{"key":"S1355617720000934_ref13","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"S1355617720000934_ref41","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3932(89)90186-3"},{"key":"S1355617720000934_ref31","doi-asserted-by":"publisher","DOI":"10.1093\/arclin\/11.4.329"},{"key":"S1355617720000934_ref28","first-page":"668","article-title":"Optimizing the preclinical Alzheimer\u2019s cognitive composite with semantic processing: The PACC5","volume":"3","author":"Papp","year":"2017","journal-title":"Alzheimer\u2019s and Dementia: Translational Research and Clinical Interventions"},{"key":"S1355617720000934_ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.03.069"},{"key":"S1355617720000934_ref38","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2015-312383"},{"key":"S1355617720000934_ref27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53221.x"},{"key":"S1355617720000934_ref2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1202753"},{"key":"S1355617720000934_ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2004.02.001"},{"key":"S1355617720000934_ref20","first-page":"130","article-title":"A composite measure of cognitive and functional progression in Alzheimer\u2019s disease: Design of the capturing changes in cognition study","volume":"3","author":"Jutten","year":"2017","journal-title":"Alzheimer\u2019s and Dementia: Translational Research and Clinical Interventions"},{"key":"S1355617720000934_ref25","doi-asserted-by":"publisher","DOI":"10.1097\/01.wad.0000213865.09806.92"},{"key":"S1355617720000934_ref4","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000279"},{"key":"S1355617720000934_ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.02.002"},{"key":"S1355617720000934_ref9","first-page":"123","article-title":"Cross-validation of optimized composites for preclinical Alzheimer\u2019s disease","volume":"3","author":"Donohue","year":"2017","journal-title":"Alzheimer\u2019s and Dementia"},{"key":"S1355617720000934_ref19","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.1971"},{"key":"S1355617720000934_ref35","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-6177(03)00039-8"},{"key":"S1355617720000934_ref29","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt222"},{"key":"S1355617720000934_ref21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.02.002"},{"key":"S1355617720000934_ref43","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(82)90033-4"},{"key":"S1355617720000934_ref15","first-page":"161","article-title":"Temporal unfolding of declining episodic memory on the Free and Cued Selective Reminding Test in the predementia phase of Alzheimer\u2019s disease: Implications for clinical trials","volume":"10","author":"Grober","year":"2018","journal-title":"Alzheimer\u2019s and Dementia: Diagnosis, Assessment and Disease Monitoring"},{"key":"S1355617720000934_ref14","unstructured":"Food and Drug Administration. (2018). Early Alzheimer\u2019s Disease: Developing Drugs for Treatment. Guidance for Industry."},{"key":"S1355617720000934_ref36","doi-asserted-by":"publisher","DOI":"10.1186\/s12877-015-0103-3"},{"key":"S1355617720000934_ref40","first-page":"498","volume-title":"Wechsler Adult Intelligence Scale\u2013Fourth Edition (WAIS\u2013IV)","volume":"22","author":"Wechsler","year":"2008"}],"container-title":["Journal of the International Neuropsychological Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1355617720000934","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T12:46:40Z","timestamp":1621342000000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1355617720000934\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,13]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["S1355617720000934"],"URL":"https:\/\/doi.org\/10.1017\/s1355617720000934","relation":{},"ISSN":["1355-6177","1469-7661"],"issn-type":[{"value":"1355-6177","type":"print"},{"value":"1469-7661","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,13]]}}}