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Background: In this systematic review we sought to characterize practice effects on traditional in-clinic or digital performance outcome measures commonly used in one of four neurologic disease areas (multiple sclerosis; Huntington's disease; Parkinson's disease; and Alzheimer's disease, mild cognitive impairment and other forms of dementia), describe mitigation strategies to minimize their impact on data interpretation and identify gaps to be addressed in future work. Methods: Fifty-eight original articles (49 from Embase and an additional 4 from PubMed and 5 from additional sources; cut-off date January 13, 2021) describing practice effects or their mitigation strategies were included. Results: Practice effects observed in healthy volunteers do not always translate to patients living with neurologic disorders. Mitigation strategies include reliable changes indices that account for practice effects or a run-in period. While the former requires data from a reference sample showing similar practice effects, the latter requires a sufficient number of tests in the run-in period to reach steady-state performance. However, many studies only included 2 or 3 test administrations, which is insufficient to define the number of tests needed in a run-in period. Discussion: Several gaps have been identified. In particular the assessment of practice effects on an individual patient level as well as the temporal dynamics of practice effects are largely unaddressed. Here, digital tests, which allow much higher testing frequency over prolonged periods of time, can be used in future work to gain a deeper understanding of practice effects and to develop new metrics for assessing and accounting for practice effects in clinical research and clinical trials.
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