학술논문

Cognitive practice effects delay diagnosis of MCI: Implications for clinical trials
Document Type
article
Source
Alzheimer's & Dementia: Translational Research & Clinical Interventions. 8(1)
Subject
Biomedical and Clinical Sciences
Clinical Sciences
Alzheimer's Disease
Aging
Dementia
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Clinical Trials and Supportive Activities
Prevention
Neurodegenerative
Acquired Cognitive Impairment
Neurosciences
Brain Disorders
Clinical Research
Detection
screening and diagnosis
4.2 Evaluation of markers and technologies
Alzheimer's disease
clinical trials
early diagnosis
longitudinal aging
mild cognitive impairment
practice effects
Alzheimer's Disease Neuroimaging Initiative
Clinical sciences
Biological psychology
Language
Abstract
IntroductionPractice 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.MethodsOf 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.ResultsIn the ADNI sample, PE-adjusted scores increased MCI incidence by 19% (P