Cognitive Practice Effects Delay Diagnosis; Implications for Clinical Trials.

Autor:	Sanderson-Cimino M; San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA., Elman JA; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA.; Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA, USA., Tu XM; Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA, USA.; Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.; Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, CA, USA., Gross AL; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MA, USA., Panizzon MS; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA.; Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA, USA., Gustavson DE; Department of Medicine, Vanderbilt University Medical Center, Nashville TN, USA., Bondi MW; Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA, USA.; Psychology Service, VA San Diego Healthcare System, San Diego, CA, USA., Edmonds EC; Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA, USA.; Research Service, VA San Diego Healthcare System, San Diego, CA, USA., Eglit GML; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA.; Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA, USA.; Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, CA, USA., Eppig JS; VA Puget Sound, Seattle Division, WA, USA., Franz CE; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA.; Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA, USA., Jak AJ; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA.; Center of Excellence for Stress and Mental Health, Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA., Lyons MJ; Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA., Thomas KR; Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA, USA.; Research Service, VA San Diego Healthcare System, San Diego, CA, USA., Williams ME; San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA., Kremen WS; Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA.; Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA, USA.; Center of Excellence for Stress and Mental Health, Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2020 Nov 05. Date of Electronic Publication: 2020 Nov 05.
DOI:	10.1101/2020.11.03.20224808
Abstrakt:	Objective: Practice effects on cognitive tests obscure decline, thereby delaying detection of mild cognitive impairment (MCI). This reduces opportunities for slowing Alzheimer's disease progression and can hinder clinical trials. Using a novel method, we assessed the ability of practice-effect-adjusted diagnoses to detect MCI earlier, and tested the validity of these diagnoses based on AD biomarkers. Methods: Of 889 Alzheimer's Disease Neuroimaging Initiative participants who were cognitively normal (CN) at baseline, 722 returned at 1-year-follow-up (mean age=74.9±6.8). Practice effects were calculated by comparing returnee scores at follow-up to demographically-matched individuals who had only taken the tests once, with an additional adjustment for attrition effects. Practice effects for each test were subtracted from follow-up scores. The lower scores put additional individuals below the impairment threshold for MCI. CSF amyloid-beta, phosphorylated tau, and total tau were measured at baseline and used for criterion validation. Results: Practice-effect-adjusted scores increased MCI incidence by 26% (p<.001). Adjustment increased proportions of amyloid-positive MCI cases (+20%) and reduced proportions of amyloid-positive CNs (-6%) (ps<.007). With the increased MCI base rate, adjustment for practice effects would reduce the sample size needed for detecting significant drug treatment effects by an average of 21%, which we demonstrate would result in multi-million-dollar savings in a clinical trial. Interpretation: Adjusting for practice effects on cognitive testing leads to earlier detection of MCI. When MCI is an outcome, this reduces recruitment needed for clinical trials, study duration, staff and participant burden, and can dramatically lower costs. Importantly, biomarker evidence also indicates improved diagnostic accuracy.
Databáze:	MEDLINE
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