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.

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.

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.

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.

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.

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.

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.

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.

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.

External validation of change formulae in neuropsychology with neuroimaging biomarkers: A methodological recommendation and preliminary clinical data.

OBJECTIVE: Within neuropsychology, a number of mathematical formulae (e.g. reliable change index, standardized regression based) have been used to determine if change across time has reliably occurred. When these formulae have been compared, they often produce different results, but 'different' results do not necessarily indicate which formulae are 'best.' The current study sought to further our understanding of change formulae by comparing them to clinically relevant external criteria (amyloid deposition and hippocampal volume). METHOD: In a sample of 25 older adults with varying levels of cognitive intactness, participants were tested twice across one week with a brief cognitive battery. Seven different change scores were calculated for each participant. An amyloid PET scan (to get a composite of amyloid deposition) and an MRI (to get hippocampal volume) were also obtained. RESULTS: Deviation-based change formulae (e.g. simple discrepancy score, reliable change index with or without correction for practice effects) were all identical in their relationship to the two neuroimaging biomarkers, and all were non-significant. Conversely, regression-based change formulae (e.g. simple and complex indices) showed stronger relationships to amyloid deposition and hippocampal volume. CONCLUSIONS: These results highlight the need for external validation of the various change formulae used by neuropsychologists in clinical settings and research projects. The findings also preliminarily suggest that regression-based change formulae may be more relevant than deviation-based change formulae in this context.

Predicting Premorbid Scores on the Repeatable Battery for the Assessment of Neuropsychological Status and their Validation in an Elderly Sample.

OBJECTIVE: Assessing cognitive change during a single visit requires the comparison of estimated premorbid abilities and current neuropsychological functioning. Although premorbid intellect has been widely examined, premorbid expectations for other cognitive abilities have received less attention. The current study sought to develop and validate premorbid estimates for the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). METHOD: Using demographic variables and an estimate of premorbid intellect, premorbid performance on the RBANS was predicted in a sample of 143 community-dwelling, cognitively intact older adults. RESULTS: On all six Indexes of the RBANS, premorbid intellect was the best predictor of current cognitive functioning, with gender adding to one of the prediction models (R2 = 0.04-0.16, ps < .02). These prediction formulae were then applied to a sample of 122 individuals with amnestic Mild Cognitive Impairment to look for discrepancies between premorbid and current RBANS scores. Despite minimal differences between premorbid and current RBANS scores in the intact sample, large, and statistically significant differences were observed in the impaired sample, especially on the Immediate Memory Index (discrepancy = -29.00, p < .001), Delayed Memory Index (discrepancy = -32.28, p < .001), and Total Scale score (discrepancy = -25.58, p < .001). CONCLUSION: Although validation in larger samples is needed, the current estimates of premorbid RBANS abilities may aid clinicians in determining change across time.

Short-term repeat cognitive testing and its relationship to hippocampal volumes in older adults.

BACKGROUND: Practice effects are improvements in cognitive test scores due to repeated exposure to testing materials. If practice effects provide information about Alzheimer's disease pathology, then they could be useful for clinical trials enrichment. The current study sought to add to the limited literature on short-term practice effects on cognitive tests and their relationship to neuroimaging biomarkers. METHODS: Twenty-five, non-demented older adults (8 cognitively intact, 17 with mild cognitive impairment) received magnetic resonance imaging and two testing sessions across one week to determine practice effects on seven neuropsychological test scores. A series of correlations examined if hippocampal volume was associated with baseline, one-week, or practice effects scores on these tests. Next, a series of stepwise multiple regression models examined which of the three test scores best predicted hippocampal volumes RESULTS: In the correlation analysis, baseline scores on 5 of the 7 tests were significantly associated with hippocampal volumes, one week scores were significantly related for 7 of the 7 tests, and practice effects scores were significantly correlated for 4 of the 7 tests. In the stepwise regression models, 5 of the 7 tests indicated that one-week scores best predicted hippocampal volumes. For the other models, baseline score and practice effects score each best predicted hippocampal volume. CONCLUSIONS: These results add to the growing body of evidence suggesting that diminished practice effects on short-term repeat testing is related to neuroimaging biomarkers of Alzheimer's disease and may serve as a screening tool for clinical practice and to enrich samples for research trials.

Amyloid Positivity Using [18F]Flutemetamol-PET and Cognitive Deficits in Nondemented Community-Dwelling Older Adults.

Little research exists examining the relationship between beta-amyloid neuritic plaque density via [18F]flutemetamol binding and cognition; consequently, the purpose of the current study was to compare cognitive performances among individuals having either increased amyloid deposition (Flute+) or minimal amyloid deposition (Flute-). Twenty-seven nondemented community-dwelling adults over the age of 65 underwent [18F]flutemetamol amyloid-positron emission tomography imaging, along with cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and select behavioral measures. Analysis of variance was used to identify the differences among the cognitive and behavioral measures between Flute+/Flute- groups. Flute+ participants performed significantly worse than Flute- participants on RBANS indexes of immediate memory, language, delayed memory, and total scale score, but no significant group differences in the endorsed level of depression or subjective report of cognitive difficulties were observed. Although these results are preliminary, [18F]flutemetamol accurately tracks cognition in a nondemented elderly sample, which may allow for better prediction of cognitive decline in late life.

Relationship between 18F-Flutemetamol uptake and RBANS performance in non-demented community-dwelling older adults.

OBJECTIVE: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has been used extensively for clinical care and in research for patients with mild cognitive impairment and Alzheimer's disease (AD); however, relatively few studies have evaluated the relationship between RBANS performance and AD imaging biomarkers. The purpose of the current study was to evaluate the association between a relatively new amyloid positron emission tomography imaging biomarker and performance on the RBANS. METHODS: Twenty-seven nondemented community-dwelling adults over the age of 65 underwent 18F-Flutemetamol amyloid- positron emission tomography imaging, along with cognitive testing using the RBANS and select behavioral measures. Partial correlation coefficients were used to identify relationships between the imaging and behavioral markers. RESULTS: After controlling for age and education, amyloid deposition and RBANS Indexes of Immediate Memory, Delayed Memory, and Total Scale score were significantly correlated (p's < .001, r's = -.73 to -.77, d's = 2.13-2.39), with greater amyloid burden being associated with lower RBANS scores. The Delayed Memory Index was particularly highly associated with 18F-Flutemetamol binding (r2 = .59, p < .001, d = 2.39). Neither 18F-Flutemetamol binding nor RBANS performance was significantly correlated with levels of depression, subjective cognitive difficulties, or premorbid intellect. CONCLUSIONS: Because of the limited use of amyloid imaging in clinical settings due to high cost and lack of reimbursement, these findings suggest that in particular RBANS Delayed Memory Index may be a cost-efficient tool to identify early signs of AD pathology, and its use may enlighten clinical decision-making regarding potential progression to dementia due to AD.

Short-term practice effects in mild cognitive impairment: Evaluating different methods of change.

Practice effects are improvements on cognitive tests as a result of repeated exposure to testing material. However, variability exists in the literature about whether patients with amnestic mild cognitive impairment (MCI) display practice effects, which may be partially due to the methods used to calculate these changes on repeated tests. The purpose of the current study was to examine multiple methods of assessing short-term practice effects in 58 older adults with MCI. The cognitive battery, which included tests of memory (Hopkins Verbal Learning Test-Revised and Brief Visuospatial Memory Test-Revised) and processing speed (Symbol Digit Modalities Test and Trail Making Test Parts A and B), was administered twice across one week. Dependent t tests showed statistically significant improvement on memory scores (ps < .01, ds = 0.8-1.3), but not on processing speed scores. Despite this, the sample showed no clinically meaningful improvement on any cognitive scores using three different reliable change indices. Regression-based change scores did identify relatively large groups of participants who showed smaller than expected practice effects, which may indicate that this method is more sensitive in identifying individuals who may portend a declining trajectory. Practice effects remain a complex construct, worthy of continued investigation in diverse clinical conditions.