Cognitive practice effects delay diagnosis of MCI: Implications for clinical trials
Abstract Introduction Practice effects (PEs) on cognitive tests obscure decline, thereby delaying detection of mild cognitive impairment (MCI). Importantly, PEs may be present even when there are performance declines, if scores would have been even lower without prior test exposure. We assessed how...
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Wiley
2022-01-01
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| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
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| Online Access: | https://doi.org/10.1002/trc2.12228 |
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| author | Mark Sanderson‐Cimino Jeremy A. Elman Xin M. Tu Alden L. Gross Matthew S. Panizzon Daniel E. Gustavson Mark W. Bondi Emily C. Edmonds Graham M.L. Eglit Joel S. Eppig Carol E. Franz Amy J. Jak Michael J. Lyons Kelsey R. Thomas McKenna E. Williams William S. Kremen Alzheimer's Disease Neuroimaging Initiative |
| author_facet | Mark Sanderson‐Cimino Jeremy A. Elman Xin M. Tu Alden L. Gross Matthew S. Panizzon Daniel E. Gustavson Mark W. Bondi Emily C. Edmonds Graham M.L. Eglit Joel S. Eppig Carol E. Franz Amy J. Jak Michael J. Lyons Kelsey R. Thomas McKenna E. Williams William S. Kremen Alzheimer's Disease Neuroimaging Initiative |
| author_sort | Mark Sanderson‐Cimino |
| collection | DOAJ |
| description | Abstract Introduction Practice effects (PEs) on cognitive tests obscure decline, thereby delaying detection of mild cognitive impairment (MCI). Importantly, PEs may be present even when there are performance declines, if scores would have been even lower without prior test exposure. We assessed how accounting for PEs using a replacement‐participants method impacts incident MCI diagnosis. Methods Of 889 baseline cognitively normal (CN) Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 722 returned 1 year later (mean age = 74.9 ± 6.8 at baseline). The scores of test‐naïve demographically matched “replacement” participants who took tests for the first time were compared to returnee scores at follow‐up. PEs—calculated as the difference between returnee follow‐up scores and replacement participants scores—were subtracted from follow‐up scores of returnees. PE‐adjusted cognitive scores were then used to determine if individuals were below the impairment threshold for MCI. Cerebrospinal fluid amyloid beta, phosphorylated tau, and total tau were used for criterion validation. In addition, based on screening and recruitment numbers from a clinical trial of amyloid‐positive individuals, we estimated the effect of earlier detection of MCI by accounting for cognitive PEs on a hypothetical clinical trial in which the key outcome was progression to MCI. Results In the ADNI sample, PE‐adjusted scores increased MCI incidence by 19% (P < .001), increased proportion of amyloid‐positive MCI cases (+12%), and reduced proportion of amyloid‐positive CNs (–5%; P’s < .04). Additional calculations showed that the earlier detection and increased MCI incidence would also substantially reduce necessary sample size and study duration for a clinical trial of progression to MCI. Cost savings were estimated at ≈$5.41 million. Discussion Detecting MCI as early as possible is of obvious importance. Accounting for cognitive PEs with the replacement‐participants method leads to earlier detection of MCI, improved diagnostic accuracy, and can lead to multi‐million‐dollar cost reductions for clinical trials. |
| format | Article |
| id | doaj-art-251744fb1c094f918787ff45a16f97bb |
| institution | Kabale University |
| issn | 2352-8737 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj-art-251744fb1c094f918787ff45a16f97bb2024-12-03T12:37:30ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372022-01-0181n/an/a10.1002/trc2.12228Cognitive practice effects delay diagnosis of MCI: Implications for clinical trialsMark Sanderson‐Cimino0Jeremy A. Elman1Xin M. Tu2Alden L. Gross3Matthew S. Panizzon4Daniel E. Gustavson5Mark W. Bondi6Emily C. Edmonds7Graham M.L. Eglit8Joel S. Eppig9Carol E. Franz10Amy J. Jak11Michael J. Lyons12Kelsey R. Thomas13McKenna E. Williams14William S. Kremen15Alzheimer's Disease Neuroimaging Initiative16San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology San Diego California USACenter for Behavior Genetics of Aging University of California San Diego La Jolla California USADepartment of Psychiatry School of Medicine University of California San Diego La Jolla California USADepartment of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USACenter for Behavior Genetics of Aging University of California San Diego La Jolla California USADepartment of Medicine Vanderbilt University Medical Center Nashville Tennessee USADepartment of Psychiatry School of Medicine University of California San Diego La Jolla California USADepartment of Psychiatry School of Medicine University of California San Diego La Jolla California USACenter for Behavior Genetics of Aging University of California San Diego La Jolla California USAVA Puget Sound Seattle Division Seattle Washington USACenter for Behavior Genetics of Aging University of California San Diego La Jolla California USACenter for Behavior Genetics of Aging University of California San Diego La Jolla California USADepartment of Psychological and Brain Sciences Boston University Boston Massachusetts USADepartment of Psychiatry School of Medicine University of California San Diego La Jolla California USASan Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology San Diego California USACenter for Behavior Genetics of Aging University of California San Diego La Jolla California USASan Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology San Diego California USAAbstract Introduction Practice effects (PEs) on cognitive tests obscure decline, thereby delaying detection of mild cognitive impairment (MCI). Importantly, PEs may be present even when there are performance declines, if scores would have been even lower without prior test exposure. We assessed how accounting for PEs using a replacement‐participants method impacts incident MCI diagnosis. Methods Of 889 baseline cognitively normal (CN) Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 722 returned 1 year later (mean age = 74.9 ± 6.8 at baseline). The scores of test‐naïve demographically matched “replacement” participants who took tests for the first time were compared to returnee scores at follow‐up. PEs—calculated as the difference between returnee follow‐up scores and replacement participants scores—were subtracted from follow‐up scores of returnees. PE‐adjusted cognitive scores were then used to determine if individuals were below the impairment threshold for MCI. Cerebrospinal fluid amyloid beta, phosphorylated tau, and total tau were used for criterion validation. In addition, based on screening and recruitment numbers from a clinical trial of amyloid‐positive individuals, we estimated the effect of earlier detection of MCI by accounting for cognitive PEs on a hypothetical clinical trial in which the key outcome was progression to MCI. Results In the ADNI sample, PE‐adjusted scores increased MCI incidence by 19% (P < .001), increased proportion of amyloid‐positive MCI cases (+12%), and reduced proportion of amyloid‐positive CNs (–5%; P’s < .04). Additional calculations showed that the earlier detection and increased MCI incidence would also substantially reduce necessary sample size and study duration for a clinical trial of progression to MCI. Cost savings were estimated at ≈$5.41 million. Discussion Detecting MCI as early as possible is of obvious importance. Accounting for cognitive PEs with the replacement‐participants method leads to earlier detection of MCI, improved diagnostic accuracy, and can lead to multi‐million‐dollar cost reductions for clinical trials.https://doi.org/10.1002/trc2.12228Alzheimer's diseaseclinical trialsearly diagnosislongitudinal agingmild cognitive impairmentpractice effects |
| spellingShingle | Mark Sanderson‐Cimino Jeremy A. Elman Xin M. Tu Alden L. Gross Matthew S. Panizzon Daniel E. Gustavson Mark W. Bondi Emily C. Edmonds Graham M.L. Eglit Joel S. Eppig Carol E. Franz Amy J. Jak Michael J. Lyons Kelsey R. Thomas McKenna E. Williams William S. Kremen Alzheimer's Disease Neuroimaging Initiative Cognitive practice effects delay diagnosis of MCI: Implications for clinical trials Alzheimer’s & Dementia: Translational Research & Clinical Interventions Alzheimer's disease clinical trials early diagnosis longitudinal aging mild cognitive impairment practice effects |
| title | Cognitive practice effects delay diagnosis of MCI: Implications for clinical trials |
| title_full | Cognitive practice effects delay diagnosis of MCI: Implications for clinical trials |
| title_fullStr | Cognitive practice effects delay diagnosis of MCI: Implications for clinical trials |
| title_full_unstemmed | Cognitive practice effects delay diagnosis of MCI: Implications for clinical trials |
| title_short | Cognitive practice effects delay diagnosis of MCI: Implications for clinical trials |
| title_sort | cognitive practice effects delay diagnosis of mci implications for clinical trials |
| topic | Alzheimer's disease clinical trials early diagnosis longitudinal aging mild cognitive impairment practice effects |
| url | https://doi.org/10.1002/trc2.12228 |
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