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.

Who Volunteers? Results From an Internet-Based Cognitive Monitoring Study of Community-Based Older Adults.

Objectives. Volunteering promotes well-being and may provide added purpose to life after retirement. Limited evidence exists regarding the characteristics and study adherence among those who participate in longitudinal studies while also volunteering outside the study. We assessed characteristics and adherence of older adults who volunteered outside of participation in a regular monthly cognitive monitoring study. Method. All 124 participants with complete data were included. Participants were from a regular cognitive monitoring study that required completion of a 15-min monthly online cognitive assessment. Analysis of covariance and logistic regression analysis were performed to examine differences between volunteers and nonvolunteers. Results. Those who volunteered outside the study were significantly less likely to be college-educated (although all participants were highly educated) but the two groups were cognitively similar. Volunteers had significantly lower scores for neuroticism. Those who volunteered also were significantly less likely to drop out but had poorer study adherence. The most frequent type of volunteering was religious activities. Volunteers were motivated mainly by altruism, although most reported multiple reasons. Conclusion. Older adults who enroll in a longitudinal research study and volunteer outside the study have similar personal characteristics as those who opt out of additional volunteering, with somewhat less education and more favorable personality traits. However, they may be more likely to drop out and need more reminders. Therefore, those who volunteer outside a study may need more attention from study administrators and potentially a more individualized schedule that works around their volunteer obligations.

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.

Validity of a verbal incidental learning measure from the WAIS-IV in older adults.

Incidental memory may reflect a form of learning in everyday life, although it is not consistently evaluated during standard neuropsychological evaluations. Further validation of a recently created measure of verbal Incidental Learning (IL) from the Wechsler Adult Intelligence Scale-IV is necessary to understand the utility of such a measure in clinical settings. Sixty-eight adults aged 50 to 89 were recruited from a Cognitive Disorders Clinic while receiving a standard neuropsychological assessment, along with two additional measures of IL. IL-Total Score was significantly correlated with immediate and delayed memory trials from standard neuropsychological tests (rs = .43 to .73, ps < .001, ds = 0.94-2.14), with worse IL performance being associated with lower memory abilities. Participants with probable Alzheimer's disease performed worse on the IL-Total Score than participants with Mild Cognitive Impairment, t(39.997) = 5.46, p < .001, d = 1.13. Given the strong relationships between this IL task and traditional memory measures in our sample, and the discrimination of IL-Total Score performance among diagnostic groups despite its short administration time, this IL task may play a role as a measure of memory in brief cognitive evaluations.

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.

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.

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.

Regulation of gene expression in the genomic context.

Metazoan life is dependent on the proper temporal and spatial control of gene expression within the many cells-essentially all with the identical genome-that make up the organism. While much is understood about how individual gene regulatory elements function, many questions remain about how they interact to maintain correct regulation globally throughout the genome. In this review we summarize the basic features and functions of the crucial regulatory elements promoters, enhancers, and insulators and discuss some of the ways in which proper interactions between these elements is realized. We focus in particular on the role of core promoter sequences and propose explanations for some of the contradictory results seen in experiments aimed at understanding insulator function. We suggest that gene regulation depends on local genomic context and argue that more holistic in vivo investigations that take into account multiple local features will be necessary to understand how genome-wide gene regulation is maintained.