In an earlier study (11
), we observed that some patients with aMCI demonstrated significant improvements on cognitive test scores after one week (i.e., practice effects), whereas other patients with aMCI did not. The current study followed those individuals over one year to examine the cognitive trajectories of these two aMCI groups. Consistent with our hypotheses, the aMCI individuals who showed large one-week practice effects remained relatively stable across one year, whereas those who minimally improved after repeated exposure to test materials declined across time. It is important to note that we used baseline cognitive scores as covariates in these analyses, so practice effects appear to have prognostic value above and beyond any baseline cognitive differences. To our knowledge, this is the first prospective study to report on the prognostic value of practice effects in predicting future cognitive outcomes in patients with aMCI.
On the RBANS Delayed Memory Index, individuals with aMCI who showed little benefit from practice effects across one week declined on this measure after one year (-10 standard score points based on estimated marginal means from ANCOVA). Conversely, individuals with aMCI who significantly benefited from practice across one week remained stable across one year (<1 standard score point). Individuals judged to be cognitively intact at baseline and one week tended to slightly improve across one year on this measure of delayed recall (+5 standard score points). These changes across time on the Delayed Memory Index for each group are depicted in , with scores adjusted for age and baseline differences between the groups. Similar, albeit smaller, changes were observed on the RBANS Indexes for Immediate Memory and Language, as well as the Total Scale score. When the ANCOVAs were repeated on only the two aMCI subgroups (i.e., without the cognitively intact subjects), the results were very similar. Since this study focused on the amnestic subtype of MCI, the declines across time on the Immediate and Delayed Memory Indexes of the RBANS were expected. Similarly, the Total Scale score of the RBANS is weighted towards memory (i.e., 2/5 of the Indexes assess learning and memory), so declines on this global measure are also not surprising. Finally, other studies have observed that non-memory domains are affected in aMCI, including confrontational naming and semantic fluency (17
), which are the two subtests that make up the RBANS Language Index.
Although the current findings are consistent with prior work (9
), it conflicts with other studies where practice effects have been largely absent in patients with MCI and early dementia (5
). Some of the discrepancies between our findings and other studies in the literature are related to methodological differences. For example, two prior studies (7
) used very long retest intervals (e.g., 1 – 3 years) and practice effects are likely to be attenuated across such periods. Additionally, other studies used alternate test forms to minimize practice effects, whereas our procedures tried to maximize practice effects by purposely using the same form of each test. One key difference between our study and those in the literature is that we looked for different subtypes of aMCI cases – those that showed minimal or large benefits from practice.
One final possibility for the discrepancy between our findings and those from the existing literature is that some of our impaired subjects might not have had aMCI. The cognitive data in and the classification analyses of the baseline cognitive scores in the Results might suggest that our MCI+PE group might reflect an “accidental” MCI group (20
) or a pre-MCI group (21
). Similarly, one could argue that our MCI−PE group might more adequately be described as multi-domain MCI, as they differed from their peers on non-memory measures. Indeed, whereas the MCI+PE group was predominantly (i.e., 96%) single domain amnestic MCI, the MCI−PE group contained more individuals with deficits in memory and other cognitive domains (e.g., 50% single domain memory impaired, 23% multidomain memory and executive functioning impaired, 15% multidomain memory, executive functioning, and attention impaired). Alternatively, our two MCI subgroups might reflect a continuum of disease phase or severity of brain dysfunction (e.g., MCI+PE being a very early case of MCI and MCI−PE being a moderate case of MCI), but that they will both eventually end up with the same outcome. Both our MCI subgroups were clearly “not normal” and “not demented,” which reflects the broader view of MCI. Both groups were also clearly identified as meeting criteria for aMCI by two neuropsychologists. Some of these semantic differences are expected as the concept of MCI continues to evolve (22
). The present findings might support changes within the defining criteria of MCI. For example, more recent MCI criteria (23
) recommend “evidence of decline over time” as a method of improving diagnostic accuracy. This new criterion for MCI might also be met by a loss of practice effects over a short period of time.
If our finding of two aMCI subtypes identified based on short-term practice effects, each with different long-term outcomes, then this would have important clinical and research implications. Assessment of short-term practice effects might allow healthcare providers to predict long-term cognitive outcomes more accurately (e.g., decline, stability, or improvement), with important ramifications for long-term patient and family planning (e.g., residential placement, durable power of attorney). Additionally, clinicians might make treatment decisions based on the likelihood of a patient getting better or worse across time. For example, a provider might offer treatment sooner to those that are declining faster. From a research standpoint, practice effects might be used as a screening measure in clinical trials. Past clinical trials in MCI have struggled to identify individuals who are most appropriate to participate in studies. For example, short-term practice effects could be used to enrich samples with cases of aMCI that won’t unexpectedly revert to normal across one year (24
). Additionally, cholinesterase inhibitors and other cognitive enhancing medications might work optimally in the more severely impaired patients who demonstrate little capacity to learn after a week (i.e., MCI−PE). However, it should be noted that although we divided our aMCI subjects into two subgroups (MCI+PE and MCI−PE), practice effects scores, like other cognitive test scores, might be better viewed on a continuum. Prior work (9
) has demonstrated that practice effects as a continuous variable also has prognostic value.
Several limitations of the current study and future directions should be noted. First, the sample sizes, especially for the two aMCI subtypes, were small and replication with larger samples is needed. Replication is also recommended because we did not control for multiple comparisons within our primary analyses, and some spurious findings may have occurred. Second, the follow-up period of one year should be extended. Third, the current method of determining change across time was decline on cognitive test scores, and future studies might consider conversion to dementia as the “gold standard” outcome measure. Fourth, the participants were a high functioning group of Caucasian retirees, with an average estimated premorbid IQ of 108 and 15+ years of education, and the generalizability of these findings to other samples (e.g., lower education, non-Caucasian) is unclear. Our sample was also 80% female, and the generalizability to a predominantly male sample is uncertain. Current participants did not undergo extensive medical work-ups (e.g., physical exam, neuroimaging) to confirm their MCI status, and information beyond cognitive test scores needs to be considered in participant classification. Lastly, there were some inconsistencies in our classification of subjects at baseline and their reclassification following one week (e.g., the RBANS Delayed Memory Index was not re-administered at one-week), and future studies could correct these inconsistencies.
In conclusion, practice effects, frequently considered to be a source of error variance in repeat cognitive testing, might hold valuable information for clinicians and researchers about prognosis in aMCI. Consistent with existing research, there appears to be two subtypes of these patients: those that remain cognitively stable across time and those that decline. The current results suggest that practice effects across one week can discriminate between these two subtypes. If replicated, then practice effects could serve as a simple, convenient, and non-invasive marker for monitoring an individual patient’s cognitive status, and they could have valuable implications for clinical practice and research. Future studies might also examine the meaning of practice effects in these cognitively impaired individuals to see if they also provide information about cognitive (e.g., role of priming, interaction with other cognitive domains) and social (e.g., test or generalized anxiety) factors, as well as underlying biological mechanisms.