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

Objective:Practice effects (PE) on cognitive testing impede our ability to accurately assess change. In particular, they hamper the detection of mild cognitive impairment (MCI) and progression to dementia by delaying the point at which test scores fall below diagnostic impairment cutoffs. When decline over time is expected, as with older adults or progressive diseases, failure to adequately address PEs may lead to inaccurate conclusions because PEs artificially boost scores while pathology-related or age-related decline reduces scores. The participant-replacement method accounts for PEs by comparing performance of demographically-matched replacement participants to returnees who have been tested previously. Unlike most methods, the participant-replacement method can separate pathology- or age-related decline from PEs; however, this method has only been used across two timepoints. Neuropsychologists tend to think that PEs level out after the first follow-up, but this issue has not been evaluated in models that allow PEs in the presence of overall decline. Including more than two timepoints makes it possible to determine if PEs level out after the first follow-up, but it is analytically challenging because individuals may not be assessed at every timepoint.Participants and Methods:We examined 1190 older adults in the Alzheimer’s Disease Neuroimaging Initiative who were cognitively unimpaired (n=809) or had MCI (n=381) at baseline. Participants completed six neuropsychological measures (Trails A, Trials B, Boston Naming Test, Category Fluency, Logical Memory, Rey Auditory Verbal Learning Task) at three timepoints (baseline, 12-month, 24-month). We implemented the participant-replacement method using generalized estimating equations in comparisons of matched returnees and replacements to calculate PEs. Propensity scores matched individuals on age, education, sex, and an estimate of premorbid functioning. Generalized estimating equations modeled PEs and age-related decline separately for each cognitive measure.Results:We observed significant PEs for 5 of the 6 measures in the cognitively unimpaired group and 4 measures in the baseline MCI group. PEs did not uniformly decrease across time; some—specifically on episodic memory measures—continued to increase beyond the first follow-up for both groups of participants. Without accounting for PEs, cognitive function appeared to improve or stay the same. In contrast, when PEs were included in the models, cognitive function appeared to decline or stay the same across time.Conclusions:The replacement method of PE adjustment revealed significant PEs across two follow-ups. PEs for episodic memory, in particular, did not level out, but actually increased after the first follow-up, two years after baseline. As expected in these older adults, accounting for PEs revealed cognitive decline, in some cases, even when PE-unadjusted scores improved. This method of assessing PEs, in turn, means earlier detection of cognitive deficits, including progression to MCI, and more accurate characterization of longitudinal change.