Practice Effects in Mild Cognitive Impairment Increase Reversion Rates and Delay Detection of New Impairments

Abstract

ObjectiveCognitive practice effects (PEs) can delay detection of progression from cognitively unimpaired to mild cognitive impairment (MCI). They also reduce diagnostic accuracy as suggested by biomarker positivity data. Even among those who decline, PEs can mask steeper declines by inflating cognitive scores. Within MCI samples, PEs may increase reversion rates and thus impede detection of further impairment. Within an MCI sample at baseline, we evaluated how PEs impact prevalence, reversion rates, and dementia progression after 1 year.MethodsWe examined 329 baseline Alzheimer’s Disease Neuroimaging Initiative MCI participants (mean age = 73.1; SD = 7.4). We identified test-naïve participants who were demographically matched to returnees at their 1-year follow-up. Since the only major difference between groups was that one completed testing once and the other twice, comparison of scores in each group yielded PEs. PEs were subtracted from each test to yield PE-adjusted scores. Biomarkers included cerebrospinal fluid phosphorylated tau and amyloid beta. Cox proportional models predicted time until first dementia diagnosis using PE-unadjusted and PE-adjusted diagnoses.ResultsAccounting for PEs increased MCI prevalence at follow-up by 9.2% (272 vs. 249 MCI), and reduced reversion to normal by 28.8% (57 vs. 80 reverters). PEs also increased stability of single-domain MCI by 12.0% (164 vs. 147). Compared to PE-unadjusted diagnoses, use of PE-adjusted follow-up diagnoses led to a twofold increase in hazard ratios for incident dementia. We classified individuals as false reverters if they reverted to cognitively unimpaired status based on PE-unadjusted scores, but remained classified as MCI cases after accounting for PEs. When amyloid and tau positivity were examined together, 72.2% of these false reverters were positive for at least one biomarker.InterpretationEven when PEs are small, they can meaningfully change whether some individuals with MCI retain the diagnosis at a 1-year follow-up. Accounting for PEs resulted in increased MCI prevalence and altered stability/reversion rates. This improved diagnostic accuracy also increased the dementia-predicting ability of MCI diagnoses.

Practice Effect of Repeated Cognitive Tests Among Older Adults: Associations With Brain Amyloid Pathology and Other Influencing Factors

“…Valid instruments and implementations of cognitive tests are essential for the evaluation of cognitive status, decline and subsequent dementia diagnosis, and the screening of at-risk participants for clinical trials and population intervention programs for dementia prevention. However, practice effects (PE) after repeated cognitive measurements, which refer to improvements in test performance due to repeated exposure to test materials or procedures ( Hausknecht et al, 2007 ; Goldberg et al, 2015 ), often mask a potential cognitive decline and remain a major issue in clinical and research settings ( Houx et al, 2002 ; Sanderson-Cimino et al, 2022 ). Failing to account for practice effects in cognitive tests could delay diagnosis and clinical care for patients with cognitive deficits.…”

Mild Cognitive Impairment, Reversion Rates, and Associated Factors: Comparison of Two Diagnostic Approaches

“…A second limitation involves reversion due to practice effects. Our participants were followed until a reversion event occurred, exposing them to multiple testing sessions, potentially leading to practice effects that masked true decline [57]. Since we implemented an extensive test battery with a larger number of non-amnestic tests, the likelihood of finding non-amnestic MCI subjects is artificially high.…”

Misinterpreting cognitive change over multiple timepoints: When practice effects meet age-related decline.

“…Using this method, it has been shown that adjusting for PEs leads to an earlier detection of MCI, improves stability of MCI diagnoses, and strengthens our ability to predict conversion to dementia (Sanderson-Cimino, Elman, Tu, Gross, Panizzon, Gustavson, Bondi, Edmonds, Eglit, et al, 2022; Sanderson-Cimino, Elman, Tu, Gross, Panizzon, Gustavson, Bondi, Edmonds, Eppig, et al, 2022). Failure to adjust for PEs also decreases statistical power and may have a substantial impact on the financial, staff, and patient burden of clinical drug trials that investigate conversation to MCI or dementia (Elman et al, 2018; Sanderson-Cimino, Elman, Tu, Gross, Panizzon, Gustavson, Bondi, Edmonds, Eglit, et al, 2022; Sanderson-Cimino, Elman, Tu, Gross, Panizzon, Gustavson, Bondi, Edmonds, Eppig, et al, 2022).…”

“…Repeated assessments are subject to practice effects (PEs) that impair our ability to detect change. PEs can be defined as improvements in performance due to familiarity with testing rather than any actual alteration of true ability; put simply, someone taking a cognitive test for the second time often does better than if they were taking it for the first time (Calamia et al, 2012; Heilbronner et al, 2010; Salthouse, 2019; Sanderson-Cimino, Elman, Tu, Gross, Panizzon, Gustavson, Bondi, Edmonds, Eppig, et al, 2022). PEs are sometimes separated into content (i.e., knowledge of specific stimuli) and context (i.e., improved familiarity with testing, reduced anxiety) effects, although this delineation is somewhat heuristic (Gross et al, 2018; Heilbronner et al, 2010).…”

“…PEs are often ignored or minimally addressed in both research and clinical settings (Calamia et al, 2012; Goldberg et al, 2015; Heilbronner et al, 2010; Machulda et al, 2017; Mathews et al, 2014; Salthouse, 2019; Sanderson-Cimino, Elman, Tu, Gross, Panizzon, Gustavson, Bondi, Edmonds, Eppig, et al, 2022). This is somewhat alarming as PEs are pervasive, occurring across all cognitive domains, and long-lasting, with studies noting PEs after up to 7 years postbaseline (Elman et al, 2018; Goldberg et al, 2015; Gross et al, 2015, 2017; Rönnlund et al, 2005).…”