Novel measures of cognition and function for the AD spectrum in the Novel Measures for Alzheimer's Disease Prevention Trials (NoMAD) project: Psychometric properties, convergent validation, and contrasts with established measures.

INTRODUCTION: This study derived composite scores for two novel cognitive measures, the No Practice Effect (NPE) battery and the Miami Computerized Functional Skills Assessment and Training system for use in early-stage Alzheimer's disease (AD) clinical trials. Their psychometric properties and associations with AD risk markers were compared to those of well-established measures. METHODS: For 291 older adults with healthy cognition or early mild cognitive impairment, Exploratory factor analyses were used to identify the factor structure of the NPE. Factor and total scores were examined for their psychometric properties and associations with AD risk biomarkers. RESULTS: Composite scores from the novel cognitive and functional measures demonstrated better psychometric properties (distribution and test-retest reliability) and stronger associations with AD-related demographic, genetic, and brain risk markers than well-established measures, DISCUSSION: These novel measures have potential for use as primary cognitive and functional outcomes in early-stage AD clinical trials. HIGHLIGHTS: Well-established cognitive tests may not accurately detect subtle cognitive changes. No Practice Effect (NPE) and Computerized Functional Skills Assessment and Training are novel measures designed to have improved psychometric properties. NPE had Executive Function, Cognitive Control/Speed, and Episodic Memory domains. Novel measures had better psychometric properties compared to established measures. Significant associations with Alzheimer's disease biomarkers were found with novel measures.

Effects of individual practice on joint musical synchronization.

Successful music-making requires precise sensorimotor synchronization, both in individual (solo) and joint (ensemble) social settings. We investigated how individual practice synchronizing with a temporally regular melody (Solo conditions) influences subsequent synchronization between two partners (Joint conditions). Musically trained adults practiced producing a melody by tapping on a keypad; each tap generated the next tone in the melody. First, the pairs synchronized their melody productions with their partner in a baseline Joint synchronization task. Then each partner separately synchronized their melody with a computer-generated recording of the partner's melody in a Solo intervention condition that presented either Normal (temporally regular) auditory feedback or delayed feedback (by 30-70 ms) in occasional (25%) randomly placed tone positions. Then the pairs synchronized again with their partner in a Joint condition. Next, they performed the second Solo condition (normal or delayed auditory feedback) followed again by the Joint condition. Joint synchronization performance was modeled with a delay-coupled oscillator model to assess the coupling strength between partners. Absolute asynchronies in the Solo Intervention tasks were greater in the Delayed feedback condition than in the Normal feedback condition. Model estimates yielded larger coupling values between partners in Joint conditions that followed the Solo Normal feedback than the Solo Delayed feedback. Notably, the asynchronies were smaller in the Joint conditions than in the Solo conditions. These findings indicate that coupled interactions in settings of two or more performers can be improved by individual synchronization practice.

Short-Term Practice Effects on Cognitive Tests Across the Late Life Cognitive Spectrum and How They Compare to Biomarkers of Alzheimer's Disease.

Background: Practice effects on cognitive testing in mild cognitive impairment (MCI) and Alzheimer's disease (AD) remain understudied, especially with how they compare to biomarkers of AD. Objective: The current study sought to add to this growing literature. Methods: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) completed a brief battery of cognitive tests at baseline and again after one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE ɛ4 status. Results: The intact participants showed significantly larger baseline cognitive scores and practice effects than the other two groups on overall composite measures. Those with MCI showed significantly larger baseline scores and practice effects than AD participants on the composite. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact > MCI > AD). For APOE ɛ4, the intact had significantly fewer copies of ɛ4 than MCI and AD. The effect sizes of the baseline cognitive scores and practice effects were comparable, and they were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons. Conclusion: Baseline cognition and short-term practice effects appear to be sensitive markers in late life cognitive disorders, as they separated groups better than commonly-used biomarkers in AD. Further development of baseline cognition and short-term practice effects as tools for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted.

Norms, convergent validity, test-retest reliability, and practice effects for verbal fluency overall performance, clustering, and switching in Spanish-speaking children.

OBJECTIVE: We conducted two empirical studies (in a cross-sectional and a longitudinal design) with the aim at establishing normative data (including norms for strategy use [i.e., clustering and switching strategies] and performance over time), and examining the convergent validity, the test-retest reliability (3-4 wks interval) and the changes in performance with practice (1 year interval) of the different verbal fluency (VF) quantitative and qualitative scores in Spanish-speaking children and adolescents. METHOD: In S1 (n = 620 6- to 15-year-old Spanish-speaking children and adolescents), MANCOVA and Pearson's correlations were employed. In S2 (n = 148 6- to 12-year-old Spanish-speaking children), intraclass correlation coefficient (ICC), paired t-tests, and Confirmatory Factor Analysis (CFA) were used. RESULTS: S1 results showed an age effect on all VF measures (quantitative and qualitative). The number of switches/clusters was more related to total word productivity and to executive functions (EF) than the mean cluster size. In S2, a significant increase in phonological VF performance was observed on number of switches and word productivity scores from baseline (Time 1) to repeat testing at Time 2. Practice effects were observed at Time 3 on all measures except for semantic and phonological mean cluster size. Test-retest reliability coefficients at Time 2 for number of clusters and switches, but not for mean cluster size, fell in the moderate range, ranging from ICCs .61 to ICCs .81. Test-retest reliability coefficients for total word productivity were higher (ICCs above .80) and stronger when testing as a unity with CFA methods (ϕ=.94, p < .001). CONCLUSIONS: These data may be relevant for informing the neuropsychological assessment of spontaneous cognitive flexibility in children with typical development (TD) and those with developmental or acquired disorders.

Test-retest reliability and reliable change index of the Philips IntelliSpace Cognition digital test battery.

OBJECTIVE: This article provides the test-retest reliability and Reliable Change Indices (RCIs) of the Philips IntelliSpace Cognition (ISC) platform, which contains digitized versions of well-established neuropsychological tests. METHOD: 147 participants (ages 19 to 88) completed a digital cognitive test battery on the ISC platform or paper-pencil versions of the same test battery during two separate visits. Intraclass correlation coefficients (ICC) were calculated separately for the ISC and analog test versions to compare reliabilities between administration modalities. RCIs were calculated for the digital tests using the practice-adjusted RCI and standardized regression-based (SRB) method. RESULTS: Test-retest reliabilities for the ISC tests ranged from moderate to excellent and were comparable to the test-retest reliabilities for the paper-pencil tests. Baseline test performance, retest interval, age, and education predicted test performance at visit 2 with baseline test performance being the strongest predictor for all outcome measures. For most outcome measures, both methods for the calculation of RCIs show agreement on whether or not a reliable change was observed. CONCLUSIONS: RCIs for the digital tests enable clinicians to determine whether a measured change between assessments is due to real improvement or decline. Together, this contributes to the growing evidence for the clinical utility of the ISC platform.

How Many Participants? How Many Trials? Maximizing the Power of Reaction Time Studies.

Due to limitations in the resources available for carrying out reaction time (RT) experiments, researchers often have to choose between testing relatively few participants with relatively many trials each or testing relatively many participants with relatively few trials each. To compare the experimental power that would be obtained under each of these options, I simulated virtual experiments using subsets of participants and trials from eight large real RT datasets examining 19 experimental effects. The simulations compared designs using the first N T trials from N P randomly selected participants, holding constant the total number of trials across all participants, N P × N T . The [ N P , N T ] combination maximizing the power to detect each effect depended on how the mean and variability of that effect changed with practice. For most effects, power was greater in designs having many participants with few trials each rather than the reverse, suggesting that researchers should usually try to recruit large numbers of participants for short experimental sessions. In some cases, power for a fixed total number of trials across all participants was maximized by having as few as two trials per participant in each condition. Where researchers can make plausible predictions about how their effects will change over the course of a session, they can use those predictions to increase their experimental power.

A Closer Look at Practice Effects in Mild Cognitive Impairment and Alzheimer's Disease.

Practice effects have become a potentially important variable regarding the diagnosis, prognosis, and treatment recommendations in mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the understanding of these short-term changes in test scores remains unclear. The current observational study sought to examine variables that influence the magnitude of short-term practice effects in MCI and AD, including demographic information, cognitive performance, daily functioning, and medical comorbidities. One hundred sixty-six older adults classified as cognitively intact, amnestic MCI, or mild AD were tested twice across 1 week with a brief battery of neuropsychological tests. Correlational and regression analyses examined the relationship of practice effects with demographic and clinical variables. Results indicated that practice effects were minimally related to demographic variables and medical comorbidities, but they were significantly related to cognitive variables, depressive symptoms, and daily functioning. These findings expand our understanding of practice effects in MCI and AD, and they may allow a better appreciation of how they could affect clinical care and research.

Simulating conversations: A Markov chain model of a central speaker's mnemonic influence over a group of communicating listeners.

Through their selective rehearsal, Central Speakers can reshape collective memory in a group of listeners, both by increasing accessibility for mentioned items (shared practice effects) and by decreasing relative accessibility for related but unmentioned items (socially shared retrieval induced forgetting, i.e., SSRIF). Subsequent networked communication in the group can further modify these mnemonic influences. Extant empirical work has tended to examine such downstream influences on a Central Speaker's mnemonic influence following a relatively limited number of interactions - often only two or three conversations. We develop a set of Markov chain simulations to model the long-term dynamics of such conversational remembering across a variety of group types, based on reported empirical data. These models indicate that some previously reported effects will stabilize in the long-term collective memory following repeated rounds of conversation. Notably, both shared practice effects and SSRIF persist into future steady states. However, other projected future states differ from those described so far in the empirical literature, specifically: the amplification of shared practice effects in communicational versus solo remembering non-conversational groups, the relatively transient impact of social (dis)identification with a Central Speaker, and the sensitivity of communicating networks to much smaller mnemonic biases introduced by the Central Speaker than groups of individual rememberers. Together, these simulations contribute insights into the long-term temporal dynamics of collective memory by addressing questions difficult to tackle using extant laboratory methods, and provide concrete suggestions for future empirical work.

Improvements in task performance after practice are associated with scale-free dynamics of brain activity.

Although practicing a task generally benefits later performance on that same task, there are individual differences in practice effects. One avenue to model such differences comes from research showing that brain networks extract functional advantages from operating in the vicinity of criticality, a state in which brain network activity is more scale-free. We hypothesized that higher scale-free signal from fMRI data, measured with the Hurst exponent (H), indicates closer proximity to critical states. We tested whether individuals with higher H during repeated task performance would show greater practice effects. In Study 1, participants performed a dual-n-back task (DNB) twice during MRI (n = 56). In Study 2, we used two runs of n-back task (NBK) data from the Human Connectome Project sample (n = 599). In Study 3, participants performed a word completion task (CAST) across six runs (n = 44). In all three studies, multivariate analysis was used to test whether higher H was related to greater practice-related performance improvement. Supporting our hypothesis, we found patterns of higher H that reliably correlated with greater performance improvement across participants in all three studies. However, the predictive brain regions were distinct, suggesting that the specific spatial H↑ patterns are not task-general.

Cognitive Trajectories in Preclinical and Prodromal Alzheimer's Disease Related to Amyloid Status and Brain Atrophy: A Bayesian Approach.

Background: Cognitive decline is a key outcome of clinical studies in Alzheimer's disease (AD). Objective: To determine effects of global amyloid load as well as hippocampus and basal forebrain volumes on longitudinal rates and practice effects from repeated testing of domain specific cognitive change in the AD spectrum, considering non-linear effects and heterogeneity across cohorts. Methods: We included 1,514 cases from three cohorts, ADNI, AIBL, and DELCODE, spanning the range from cognitively normal people to people with subjective cognitive decline and mild cognitive impairment (MCI). We used generalized Bayesian mixed effects analysis of linear and polynomial models of amyloid and volume effects in time. Robustness of effects across cohorts was determined using Bayesian random effects meta-analysis. Results: We found a consistent effect of amyloid and hippocampus volume, but not of basal forebrain volume, on rates of memory change across the three cohorts in the meta-analysis. Effects for amyloid and volumetric markers on executive function were more heterogeneous. We found practice effects in memory and executive performance in amyloid negative cognitively normal controls and MCI cases, but only to a smaller degree in amyloid positive controls and not at all in amyloid positive MCI cases. Conclusions: We found heterogeneity between cohorts, particularly in effects on executive functions. Initial increases in cognitive performance in amyloid negative, but not in amyloid positive MCI cases and controls may reflect practice effects from repeated testing that are lost with higher levels of cerebral amyloid.

Augmented Visual Feedback for Complex Motor Skill Acquisition: A Demonstration with Healthy Young Adults.

Mirror therapy (MT) is a treatment for improving motor function after stroke. Video therapy (VT) training combines observation and imitation of video clips, and it has been used to conduct efficient occupational therapy. We sought to determine the effects of MT and VT on tool-use with healthy young adults. We assigned participants to three different training groups in which they used their non-dominant left hands to move a ball with chopsticks: (a) a self-paced MT group (N = 14), (b) an MT group who moved the ball while looking at the mirror image of the right hand with a sound cue (4-second intervals) (N = 12), and (c) a group who imitated a video demonstration (4-second intervals) (N = 13). The ball-moving time was significantly reduced after training in all three groups: MT group (p < .001), MT-R group (p = .010), and VT group (p = .014), but the video group showed significantly greater relative improvements in motion variability (p = .030) and object prediction (p = .008).We concluded that MT was as effective as VT in improving movement speed, but, with these healthy young adults, MT was less effective than VT in learning speed control or hand pre-shaping to refine task movements for tool use.

Does Frequency of Baseline Testing Influence Concussion Diagnostic Decision Making Among College Athletes.

OBJECTIVE: Concussion is a growing public health concern given the large number of youth and collegiate athletes participating in collision sports. Sport-related concussions can have an adverse impact on student-athletes' health and academic performance. Athletic programs within academic organizations are motivated to employ the most effective and efficient diagnostic and recovery procedures to minimize the duration and impact of these symptoms on student-athletes' functioning. The present study sought to further our understanding regarding the value and frequency of conducting baseline assessments when evaluating sport-related concussions. METHOD: A total of 41 athletes (24 men, 17 women) between the ages of 18 and 22 were evaluated following suspected concussive injury between 2015 and 2018. Post-injury test results were compared to baselines that had been collected either 1 or 2 years prior, and to normative data, to determine consistency in diagnostic outcomes. RESULTS: Baseline test/retest reliability using Pearson's bivariate correlations revealed modest correlations on measures of verbal and visual memory (0.437-0.569) and very strong correlations on measures of reaction time and visual-motor speed (0.811-0.821). Meanwhile, minimal if any differences in clinical decision-making regarding the diagnostic outcome was observed when comparing post-injury test results to different baselines and to normative data. CONCLUSIONS: Findings indicate that yearly baseline testing may not improve diagnostic accuracy, and in many cases, normative data may be adequate for decision-making. Additional research should evaluate the potential benefit of baseline testing in return-to-play decision-making among broader athletic populations.

Pragmatic approaches to handling practice effects in longitudinal cognitive aging research.

INTRODUCTION: The challenge of accounting for practice effects (PEs) when modeling cognitive change was amplified by the COVID-19 pandemic, which introduced period and mode effects that may bias the estimation of cognitive trajectory. METHODS: In three Kaiser Permanente Northern California prospective cohorts, we compared predicted cognitive trajectories and the association of grip strength with cognitive decline using three approaches: (1) no acknowledgment of PE, (2) inclusion of a wave indicator, and (3) constraining PE based on a preliminary model (APM) fit using a subset of the data. RESULTS: APM-based correction for PEs based on balanced, pre-pandemic data, and with current age as the timescale produced the smallest discrepancy between within-person and between-person estimated age effects. Estimated associations between grip strength and cognitive decline were not sensitive to the approach used. DISCUSSION: Constraining PEs based on a preliminary model is a flexible, pragmatic approach allowing for meaningful interpretation of cognitive change. HIGHLIGHTS: The magnitude of practice effects (PEs) varied widely by study. When PEs were present, the three PE approaches resulted in divergent estimated age-related cognitive trajectories. Estimated age-related cognitive trajectories were sometimes implausible in models that did not account for PEs. The associations between grip strength and cognitive decline did not differ by the PE approach used. Constraining PEs based on estimates from a preliminary model allows for a meaningful interpretation of cognitive change.

Verbal and visual learning ability in patients with treatment-resistant schizophrenia: A 1-year follow-up study.

Objective: In the general population, repeated cognitive testing produces learning effects with potential for improved test performance. It is currently unclear whether the same effect of repeated cognitive testing on cognition pertains to people living with schizophrenia, a condition often associated with significant cognitive impairments. This study aims to evaluate learning ability in people with schizophrenia and-considering the evidence that antipsychotic medication can additionally impair cognitive performance-explore the potential impact of anticholinergic burden on verbal and visual learning. Method: The study included 86 patients with schizophrenia, treated with clozapine, who had persisting negative symptoms. They were assessed at baseline, weeks 8, 24 and 52 using Positive and Negative Syndrome Scale, Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-R (BVMT-R). Results: There were no significant improvements in verbal or visual learning across all measurements. Neither the clozapine/norclozapine ratio nor anticholinergic cognitive burden significantly predicted participants' total learning. Premorbid IQ was significantly associated with verbal learning on the HVLT-R. Conclusions: These findings advance our understanding of cognitive performance in people with schizophrenia and demonstrate limited learning performance in individuals with treatment-refractory schizophrenia.

Four year practice effects on the RBANS in a longitudinal study of older adults.

OBJECTIVE: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a widely used measure in neuropsychological assessment. Studies of practice effects on the RBANS have typically been assessed over one or two repeated assessments. The aim of the current study is to examine practice effects across four-years after baseline in a longitudinal study of cognitively healthy older adults. METHOD: 453 Participants from the Louisiana Aging Brain Study (LABrainS) completed the RBANS Form A on up to four annual assessments after baseline. Practice effects were calculated using a modified participants-replacement method where scores of returnees are compared to the baseline scores of matched participants with additional adjustment for attrition effects. RESULTS: Practice effects were observed primarily in the immediate memory, delayed memory, and total score indices. These index scores continued to increase with repeated assessments. CONCLUSIONS: These findings extend past work on the RBANS showing the susceptibility of memory measures to practice effects. Given that memory and total score indices of the RBANS have the most robust relationships with pathological cognitive decline, these findings raise concerns about the ability to recruit those at risk for decline from longitudinal studies using the same form of the RBANS for multiple years.

Computerized cognitive practice effects in relation to amyloid and tau in preclinical Alzheimer's disease: Results from a multi-site cohort.

Scalable cognitive paradigms that provide metrics such as the Computerized Cognitive Composite (C3) may be sensitive enough to relate to Alzheimer's disease biomarkers in the preclinical clinically unimpaired (CU) stage. We examined CU older adults (n = 3287) who completed alternate versions of the C3 approximately 51 days apart. A subset of CU with abnormal amyloid also completed tau positron emission tomography (PET) imaging. C3 initial performance and practice effects were examined in relation to amyloid status and continuous regional tau burden. Initial C3 performance was associated with amyloid status across all participants, and with tau burden in the medial temporal lobe and early cortical regions in CU with abnormal amyloid. Short-term practice effects were associated with reduced tau in these regions in CU with abnormal amyloid, but were not associated with amyloid status. Thus, computerized cognitive testing repeated over a short follow-up period provides additional insights into early Alzheimer's disease processes.

Tracking cognition with the T-MoCA in a racially/ethnically diverse older adult cohort.

Introduction: We investigated the utility of the Telephone-Montreal Cognitive Assessment (T-MoCA) to track cognition in a diverse sample from the Einstein Aging Study. Methods: Telephone and in-person MoCA data, collected annually, were used to evaluate longitudinal cognitive performance. Joint models of T-MoCA and in-person MoCA compared changes, variance, and test-retest reliability measured by intraclass correlation coefficient by racial/ethnic group. Results: There were no significant differences in baseline performance or longitudinal changes across three study waves for both MoCA formats. T-MoCA performance improved over waves 1-3 but declined afterward. Test-retest reliability was lower for the T-MoCA than for the in-person MoCA. In comparison with non-Hispanic Whites, non-Hispanic Blacks and Hispanics performed worse at baseline on both MoCA formats and showed lower correlations between T-MoCA and in-person versions. Conclusions: The T-MoCA provides valuable information on cognitive change, despite racial/ethnic disparities and practice effects. We discuss implications for health disparity populations. Highlights: We assessed the comparability of Telephone-Montreal Cognitive Assessment (T-MoCA) and in-person MoCA for tracking cognition.Changes within 3 years in T-MoCA were similar to that for the in-person MoCA.T-MoCA is subject to practice effects and shows difference in performance by race/ethnicity.Test-retest reliability of T-MoCA is lower than that for in-person MoCA.

Effects of Repeated Administration and Comparability of Alternate Forms for the Global Neuropsychological Assessment (GNA).

The Global Neuropsychological Assessment (GNA) is an extremely brief battery of cognitive tasks assessing episodic memory, processing speed, working memory, verbal fluency, executive function, and mood. It can be given in under 15 minutes, has five alternate forms, and does not require an examinee to be literate. The purpose of this study was to quantify practice effects over repeated administrations and assess comparability of the GNA's five alternate forms, preparing the battery for repeated administration in research and clinical settings. Forty participants each completed all five GNA forms at weekly intervals following a Latin square design (i.e., each form was administered at every position in the sequence an equal number of times). In a cognitively intact population, practice effects of 0.56 to 1.06 SD were observed across GNA measures when comparing the first and fifth administration. Most GNA tests showed nonsignificant interform differences with cross-form means differing by 0.35 SD or less, with the exception of modest but statistically significant interform differences for the GNA Story Memory subtest across all five forms. However, post hoc analysis identified clusters of two and three Story Memory alternate forms that were equivalent.

Three-month Practice Effect of the National Institutes of Health Toolbox Cognition Battery in Young Healthy Adults.

The National Institutes of Health Toolbox-Cognition Battery (NIHTB-CB) is a tablet-based cognitive assessment intended for individuals with neurological diseases of all ages. NIHTB-CB practice effects (PEs), however, need clarification if this measure is used to track longitudinal change. We explored the test-retest PEs on NIHTB-CB performance at 3 months in young healthy adults (n = 22). We examined corrected T-scores normalized for demographic factors and calculated PEs using Cohen's d. There were significant PEs for all NIHTB-CB composite scores and on 4/7 subtests. This work suggests the need to further assess NIHTB-CB PEs as this may affect the interpretation of study results incorporating this battery.