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.

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.

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.

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.

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.