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.

Change on the Repeatable Battery for the Assessment of Neuropsychological Status and its relationship to brain amyloid.

BACKGROUND: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has been associated with commonly used biomarkers of Alzheimer's disease (AD), including brain amyloid plaque density. However, less is known about if changes in the RBANS across time are also related to brain amyloid deposition. The current study sought to expand on prior work by examining the relationship between changes over time on the RBANS and amyloid deposition via positron emission tomography (PET). METHOD: One-hundred twenty-six older adults with intact or impaired cognition and daily functioning underwent repeat assessment with the RBANS across nearly 16 months, as well as had a baseline amyloid PET scan. RESULTS: In the entire sample, amyloid deposition was significantly related to change on all five Indexes and the Total Scale score of the RBANS, with greater amyloid being associated with worsening cognition. This pattern was also observed in 11 of 12 subtests. CONCLUSIONS: Whereas prior studies have identified a relationship between baseline RBANS and amyloid status, the current findings support that changes in the RBANS are also indicative of AD brain pathology, even if these findings are mediated by cognitive status. Although replication in a more diverse sample is needed, these results continue to support the use of the RBANS in AD clinical trials.

Repeatable battery for the assessment of neuropsychological status and its relationship to biomarkers of Alzheimer's disease.

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has been associated with commonly used biomarkers of Alzheimer's disease (AD). However, prior studies have typically utilized small and poorly characterized samples, and they have not analyzed the subtests of the RBANS. The current study sought to expand on prior work by examining the relationship between the Indexes and subtest scores of the RBANS and three AD biomarkers: amyloid deposition via positron emission tomography, hippocampal volume via magnetic resonance imaging, and APOE ε4 status.One-hundred twenty-one older adults across the AD continuum (intact, amnestic Mild Cognitive Impairment, mild AD), who were mostly Caucasian and well-educated, underwent assessment with the RBANS and collection of the three biomarkers.Greater amyloid deposition was significantly related to lower scores on all five Indexes and the Total Scale score of the RBANS, as well as 11 of 12 subtests. For bilateral hippocampal volume, significant correlations were observed for 4 of the 5 Indexes, Total Scale score, and 9 of 12 subtests, with smaller hippocampi being related to lower RBANS scores. Participants with at least one APOE ε4 allele had significantly lower scores on 3 of the 5 Indexes, Total Scale score, and 8 of the 12 subtests.In this sample of participants across the dementia spectrum, most RBANS Indexes and subtests showed relationships with the amyloid deposition, hippocampal volumes, and APOE status, with poorer performance on the RBANS being associated with biomarker positivity. Although memory scores on the RBANS have traditionally been linked to biomarkers in AD, other Index and subtest scores also hold promise as indicators of AD. Replication in a more diverse sample is needed.

Predicting daily functioning with the modified Telephone Interview for Cognitive Status.

BACKGROUND: The modified Telephone Interview for Cognitive Status (mTICS) is a frequently used telephone-based cognitive screening measure that can distinguish between normal aging, mild cognitive impairment (MCI), and dementia. Although it has been used to predict current and future cognitive function in older adults, no studies have examined if the mTICS can predict daily functioning. AIMS: The current study sought to examine the relationship between the mTICS and a performance-based measure of daily functioning. METHODS: The mTICS and demographic information (age, sex, education) were collected during a telephone screening visit for 149 older adults (65-91 years in age) with amnestic MCI. Three subscales of the Independent Living Scales (ILS; Managing Money, Managing Home and Transportation, Health and Safety) were collected during a baseline visit and during a 16 month follow-up visit in a subsample of 93 individuals. RESULTS: Using simple hierarchical regression, baseline mTICS total score combined with demographic variables significantly predicted 19-22% of baseline ILS subscale scores. Similarly, in a subsample of 93 participants with 16 month follow-up data, baseline mTICS and demographic information predicted 9-31% of ILS subscale scores at follow-up. CONCLUSIONS: The mTICS appears able to predict daily functioning in older individuals with MCI. Remote tracking of cognition and daily functioning in this at-risk group seems particularly beneficial to geriatricians and other providers, especially during COVID-19.

Validation of HVLT-R, BVMT-R, and RBANS Learning Slope Scores along the Alzheimer's Continuum.

BACKGROUND: The learning ratio (LR) is a novel learning slope score that has been developed to reduce the inherent competition between the first trial and subsequent trials in traditional learning slopes. In essence, the LR is the number of items learned after the first trial divided by the number of items yet to be learned. Criterion and convergent validation of this LR score is warranted to understand its sensitivity along the Alzheimer's disease (AD) continuum. METHOD: The LR metric was calculated for 123 participants from standard measures of memory, including the Hopkins Verbal Learning Test-Revised, Brief Visuospatial Memory Test-Revised, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) list learning, and RBANS story memory. All participants were categorized as normal cognition, mild cognitive impairment (MCI), or AD. LR performances were compared between groups, among other standard memory measures, and with regards to how well they discriminated cognitively impaired from unimpaired samples-and within diagnostic subgroups. RESULTS: Lower LR scores were observed for the MCI and AD groups than the normal cognition group, with the AD group performing worse than the MCI group for several slope calculations. Lower LR scores were also consistently associated with poorer performances on traditional memory measures. LR scores further displayed excellent receiver operator characteristics when differentiating those with and without cognitive impairment-and MCI from normal cognition. Overall, LR scores consistently outperformed traditional learning slope calculations across all analyses. CONCLUSIONS: This LR score is sensitive to memory dysfunction along the AD continuum, and results offer criterion and convergent validity for use of the LR metric to understand learning capacity.

Validation of one-year reliable change in the RBANS for community-dwelling older adults with amnestic mild cognitive impairment.

Objective: The current study sought to externally validate previously published standardized regression-based (SRB) equations for the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Indexes administered twice over a one-year period. Method: Hammers and colleagues' SRB prediction equations were applied to two independent samples of community-dwelling older adults with amnestic Mild Cognitive Impairment (MCI), including those recruited from the community (n = 64) and those recruited from a memory disorders clinic (n = 58). Results: While Observed Baseline and Observed Follow-up performances were generally comparable for both MCI samples over one year, both samples possessed significantly lower Observed One-Year Follow-up scores than were predicted based on Hammers and colleagues' development sample across many RBANS Indexes. Relatedly, both amnestic MCI samples possessed a greater percentage of participants either "declining" or failing to exhibit a long-term practice effect over one year relative to expectation across most Indexes. Further, the clinic-recruited amnestic MCI sample displayed worse baseline performances, smaller long-term practice effects, and greater proportions of individual participants exhibiting a decline across one year relative to the community amnestic MCI sample. Conclusions: These findings validate Hammers and colleagues' SRB prediction equations by (1) indicating their ability to identify clinically meaningful change across RBANS Indexes in independent samples, and (2) discriminating rates of cognitive change among cognitively nuanced samples.

Longitudinal changes on the Independent Living Scale in amnestic mild cognitive impairment.

The Independent Living Scales (ILS) is an objective measure of day-to-day functioning, which can be used to aid in diagnosing dementia in older adults with cognitive impairments. However, no studies have examined this measure longitudinally in individuals with mild cognitive impairment (MCI), a prodromal phase of dementia. Three subscales of the ILS (Managing Money, Managing Home and Transportation, Health and Safety) were administered to a sample of 94 individuals with amnestic MCI twice across 15 months. A measure of global cognition (Total Scale score on the Repeatable Battery for the Assessment of Neuropsychological Status [RBANS]) was also administered twice. In this MCI sample, two of the three subscales of the ILS showed a significant decline over time, where the third ILS subscale and the Total Scale score of the RBANS did not change. Regression-based change models showed that baseline ILS scores were most strongly predictive of follow-up ILS scores compared to RBANS scores at baseline and follow-up and demographic variables (age, education, and sex). These results provide additional information on the longitudinal change on the ILS in a sizeable cohort of older individuals with amnestic MCI, which may make this scale more useful in identifying progression to dementia.

Relationship between a novel learning slope metric and Alzheimer's disease biomarkers.

The Learning Ratio (LR) is a novel learning score examining the proportion of information learned over successive learning trials relative to information available to be learned. Validation is warranted to understand LR's sensitivity to Alzheimer's disease (AD) pathology. One-hundred twenty-three participants across the AD continuum underwent memory assessment, quantitative brain imaging, and genetic analysis. LR scores were calculated from the HVLT-R, BVMT-R, RBANS List Learning, and RBANS Story Memory, and compared to total hippocampal volumes,18F-Flutemetamol composite SUVR uptake, and APOE ε4 status. Lower LR scores were consistently associated with smaller total hippocampal volumes, greater cerebral ß-amyloid deposition, and APOE ε4 positivity. This LR score outperformed a traditional learning slope calculation in all analyses. LR is sensitive to AD pathology along the AD continuum - more so than a traditional raw learning score - and reducing the competition between the first trial and subsequent trials can better depict learning capacity.

Computerized Cognitive Training in Amnestic Mild Cognitive Impairment: A Randomized Clinical Trial.

OBJECTIVE: Computerized cognitive training has been successful in healthy older adults, but its efficacy has been mixed in patients with amnestic Mild Cognitive Impairment (MCI). METHODS: In a randomized, placebo-controlled, double-blind, parallel clinical trial, we examined the short- and long-term efficacy of a brain-plasticity computerized cognitive training in 113 participants with amnestic MCI. RESULTS: Immediately after 40-hours of training, participants in the active control group who played computer games performed better than those in the experimental group on the primary cognitive outcome (p = 0.02), which was an auditory memory/attention composite score. There were no group differences on 2 secondary outcomes (global cognitive composite and rating of daily functioning). After 1 year, there was no difference between the 2 groups on primary or secondary outcomes. No adverse events were noted. CONCLUSIONS: Although the experimental cognitive training program did not improve outcomes in those with MCI, the short-term effects of the control group should not be dismissed, which may alter treatment recommendations for these patients.

Validating 1-Year Reliable Change Methods.

OBJECTIVE: reliable change methods can assist in the determination of whether observed changes in performance are meaningful. The current study sought to validate previously published 1-year standardized regression-based (SRB) equations for commonly administered neuropsychological measures that incorporated baseline performances, demographics, and 1-week practice effects. METHOD: Duff et al.'s SRB prediction equations were applied to an independent sample of 70 community-dwelling older adults with either normal cognition or mild cognitive impairment, assessed at baseline, at 1 week, and at 1 year. RESULTS: minimal improvements or declines were seen between observed baseline and observed 1-year follow-up scores, or between observed 1-year and predicted 1-year scores, on most measures. Relatedly, a high degree of predictive accuracy was observed between observed 1-year and predicted 1-year scores across cognitive measures in this repeated battery. CONCLUSIONS: these results, which validate Duff et al.'s SRB equations, will permit clinicians and researchers to have more confidence when predicting cognitive performance on these measures over 1 year.

Reliable change in cognition over 1 week in community-dwelling older adults: a validation and extension study.

OBJECTIVE: Reliable change methods can aid neuropsychologists in understanding if performance differences over time represent clinically meaningful change or reflect benefit from practice. The current study sought to externally validate the previously published standardized regression-based (SRB) prediction equations developed by Duff for commonly administered cognitive measures. METHOD: This study applied Duff's SRB prediction equations to an independent sample of community-dwelling participants with amnestic mild cognitive impairment (MCI) assessed twice over a 1-week period. A comparison of MCI subgroups (e.g., single v. multi domain) on the amount of change observed over 1 week was also examined. RESULTS: Using pairwise t-tests, large and statistically significant improvements were observed on most measures across 1 week. However, the observed follow-up scores were consistently below expectation compared with predictions based on Duff's SRB algorithms. In individual analyses, a greater percentage of MCI participants showed smaller-than-expected practice effects based on normal distributions. In secondary analyses, smaller-than-expected practice effects were observed in participants with worse baseline memory impairment and a greater number of impaired cognitive domains, particularly for measures of executive functioning/speeded processing. CONCLUSIONS: These findings help to further support the validity of Duff's 1-week SRB prediction equations in MCI samples and extend previous research by showing incrementally smaller-than-expected benefit from practice for increasingly impaired amnestic MCI subtypes.

Recognition subtests for the Repeatable Battery for the Assessment of Neuropsychological Status: Preliminary data in cognitively intact older adults, amnestic Mild Cognitive Impairment, and Alzheimer's disease.

Objective: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has three delayed recall subtests (list, story, figure), but only one delayed recognition subtest (list). Since comparisons between delayed recall and recognition can be useful in clinical neuropsychology, the current study sought to develop and preliminarily examine two proposed new subtests for Form A of the RBANS, Story Recognition and Figure Recognition. Method: A sample of older adults who were cognitively intact (n = 48) or classified with amnestic Mild Cognitive Impairment (MCI, n = 29) or mild Alzheimer's disease (AD, n = 24) were administered the RBANS and the two new recognition subtests. Results: In the primary analyses, cognitively intact participants performed significantly better than the two memory-impaired groups on all twelve scores (one recall and three recognition [total, hits, false positive errors] for the list, story, and figure). For amnestic MCI and AD participants, they showed statistically comparable scores on 7 of the 12 variables, where those with MCI performed better than those with AD on the other five scores. Across the three groups, effect sizes were large (e.g., Cohen's d = 1.0-2.9). In secondary analyses, all of the List Recall and Recognition scores significantly correlated with one another, and this pattern was observed for all of the Story Recall and Recognition scores and most of the Figure Recall and Recognition scores. Conclusions: Although preliminary, these new recognition scores appear to provide useful information and may improve the sensitivity of the RBANS in identifying cortical/subcortical profiles in clinical and research settings.

Validation of one-week reliable change methods in cognitively intact community-dwelling older adults.

OBJECTIVE: Reliable change methods can assist the determination of whether observed changes in performance are meaningful. The current study sought to validate previously published standardized regression-based (SRB) equations for commonly administered cognitive tests using a cognitively intact sample of older adults, and extend findings by including relevant demographic and test-related variables known to predict cognitive performance. Method: This study applied previously published SRB prediction equations to 107 cognitively intact older adults assessed twice over one week. Prediction equations were also updated by pooling the current validation sample with 93 cognitively intact participants from original development sample to create a combined development sample. Results: Significant improvements were seen between observed baseline and follow-up scores on most measures. However, few differences were seen between observed follow-up scores and those predicted from these SRB algorithms, and the level of practice effects observed based on these equations were consistent with expectations. When SRBs were re-calculated from this combined development sample, predicted follow-up scores were mostly comparable with these equations, but standard errors of the estimate were consistently smaller. Conclusions: These results help support the validity of of these SRB equations to predict cognitive performance on these measures when repeated administration is necessary over short intervals. Findings also highlight the utility of expanding SRB models when predicting follow-up performance serially to provide more accurate assessment of reliable change at the level of the individual. As short-term practice effects are shown to predict cognitive performance annually, they possess the potential to inform clinical decision-making about individuals along the Alzheimer's continuum.

Predicting biomarkers in intact older adults and those with amnestic Mild Cognitive Impairment, and mild Alzheimer's Disease using the Repeatable Battery for the Assessment of Neuropsychological Status.

INTRODUCTION: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has been associated, to varying degrees, with commonly used biomarkers of Alzheimer's disease (AD). Given the ease of RBANS administration as a screening tool for clinical trials and other applications, a better understanding of how RBANS performance is associated with presence of APOE ε4 allele[s], cerebral amyloid burden, and hippocampal volume is warranted. METHOD: One hundred twenty-one older adults who were classified as intact, amnestic Mild Cognitive Impairment, or mild AD underwent cognitive assessment with the RBANS, genetic analysis, and quantitative brain imaging. APOE ε4 carrier status, 18F-Flutemetamol composite standardized uptake value ratio (SUVR), and hippocampal volume were each regressed on demographic variables and RBANS Total Scale score, Index scores, and subtest scores. RESULTS: Lower RBANS Total Scale score or Delayed Memory Index (DMI) predicted the presence of APOE ε4 allele[s], higher cerebral amyloid burden, and lower hippocampal volumes. DMI was a slightly better predictor than Total Scale score for most AD biomarkers. No demographic variables consistently contributed to these models. CONCLUSIONS: The RBANS - DMI in particular - is sensitive to AD pathology. As such, it could be used as a predictive tool, particularly in clinical drug trials to enrich samples prior to less accessible AD biomarker investigation.

The independent living scale in amnestic mild cognitive impairment: Relationships to demographic variables and cognitive performance.

INTRODUCTION: The Independent Living Scales (ILS) is an objective measure of day-to-day functioning, which can be used to aid in diagnosing dementia in older adults with cognitive impairments. However, no studies have examined this measure in individuals with Mild Cognitive Impairment (MCI), a prodromal phase of dementia. METHOD: Therefore, we sought to examine three subscales of the ILS (Managing Money, Managing Home and Transportation, Health and Safety) in a sample of 132 individuals with amnestic MCI, focusing on the relationship of the ILS with demographic variables (age, education, sex) and cognitive abilities (assessed with the Repeatable Battery for the Assessment of Neuropsychological Status [RBANS]). RESULTS: This MCI sample showed intact daily functioning on the three ILS subscales. In a series of three, separate hierarchical linear regression models, the Managing Money, Managing Home and Transportation, and Health and Safety subscales were all significantly related to demographic variables, and the RBANS Total Scale score significantly added to all models. These models would also allow one to predict an ILS score based on demographic and cognitive data, which could be compared to an observed ILS score to see if it meets expectations. CONCLUSIONS: Overall, these results indicate that daily functioning, as measured with the ILS, is related to cognitive abilities in amnestic MCI, and that demographic variables also influenced ILS scores in this cohort. Although the ILS may be appropriate for identifying functional abilities in MCI, the consideration of these moderating variables seems necessary.

Generalizability of reliable change equations for the RBANS over one year in community-dwelling older adults.

Objective: Reliable change methods can assist neuropsychologists in determining whether observed changes in a patient's performance are clinically meaningful. The current study sought to validate previously published standardized regression-based (SRB) equations for the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Indexes and subtests.Methods: Duff and colleagues's SRB prediction equations, developed from 223 cognitively intact primary care patients, were applied to an independent sample of robustly cognitively intact (n = 129) community-dwelling older adults assessed with the RBANS twice over a one-year period.Results: Results suggest that the cognitively intact participants in the current validation sample possessed significantly better Observed Follow-up scores than was predicted based on Duff's developmental sample across most RBANS Indexes and many RBANS subtests, though significantly lower Observed Follow-up scores were observed for the Visuospatial/Constructional Index than was predicted. As a result of these findings, the current study calculated updated prediction algorithms for the RBANS Index and subtest scores from the sample of 129 cognitively intact participants.Conclusions: Duff's 2004 and 2005 SRB prediction equations for the RBANS Index and subtest scores failed to generalize to a sample of cognitively intact community-dwelling participants recruited from senior living centers and independent assisted living facilities. These updated SRB prediction equations - being developed from a more medically "clean" sample of cognitively intact older adults who remained stable over 12 months - have the potential to provide a more accurate assessment of reliable change in an individual patient.