Variations in the APOE allele or BDNF Val66Met polymorphism are not associated with changes in cognitive function following a tertiary education intervention in older adults: the Tasmanian Healthy Brain Project.

The apolipoprotein (APOE) ε4 allele and the Met variant of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism are associated with reduced cognitive function in older adults. The aim of this study was to examine the independent and interactional effect of the APOE ε4 allele and BDNF Val66Met polymorphism on cognitive function in a cohort of healthy older adults who had undertaken further university level education. Multiple group latent growth curve modeling revealed no change in cognitive function over time in APOE ε4-carriers or in BDNF Met-carriers, nor in carriers of both APOE-ε4 and BDNF-Met alleles. Further, the results indicate that allelic variation in either APOE or BDNF does not modify the beneficial effects of a university-based education intervention on cognitive function over a 4-year period following the intervention

Sending Your Grandparents to University Increases Cognitive Reserve: The Tasmanian Healthy Brain Project.

Increasing an individual’s level of cognitive reserve (CR) has been suggested as a nonpharmacological approach to reducing the risk for Alzheimer’s disease. We examined changes in CR in older adults participating over 4 years in the Tasmanian Healthy Brain Project. Method: A sample of 459 healthy older adults between 50 and 79 years of age underwent a comprehensive annual assessment of current CR, neuropsychological function, and psychosocial factors over a 4-year period. The intervention group of 359 older adults (M � 59.61 years, SD � 6.67) having completed a minimum of 12 months part-time university study were compared against a control reference group of 100 adults (M � 62.49 years, SD � 6.24) who did not engage in further education. Results: Growth mixture modeling demonstrated that 44.3% of the control sample showed no change in CR, whereas 92.5% of the further education participants displayed a significant linear increase in CR over the 4 years of the study. These results indicate that older adults engaging in high-level mental stimulation display an increase in CR over a 4-year period. Conclusion: Increasing mental activity in older adulthood may be a viable strategy to improve cognitive function and offset cognitive decline associated with normal aging

ImageSURF: An ImageJ Plugin for Batch Pixel-Based Image Segmentation Using Random Forests

Image segmentation is a necessary step in automated quantitative imaging. ImageSURF is a macro-compatibleImageJ2/FIJI plugin for pixel-based image segmentation that considers a range of image derivatives totrain pixel classifiers which are then applied to image sets of any size to produce segmentations withoutbias in a consistent, transparent and reproducible manner. The plugin is available from ImageJ update sitehttp://sites.imagej.net/ImageSURF/ and source code from https://github.com/omaraa/ImageSURF

Environmental novelty exacerbates stress hormones and Aβ pathology in an Alzheimer’s model

Cognitive stimulation has been proposed as a non-pharmacological intervention to be used in primary, secondary and tertiary prevention approaches for Alzheimer’s disease. A common familial Alzheimer’s disease transgenic model showed heightened levels of the stress hormone, corticosterone. When exposed to periodic enhanced cognitive stimulation, these animals demonstrated further heightened levels of corticosterone as well as increased Aβ pathology. Hence, Alzheimer’s disease may be associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction, causing stimulatory environments to become stress-inducing, leading to a glucocorticoid-pathology cycle contributing to further Aβ release and plaque formation. This finding suggests that stimulation-based interventions and local environments for people with Alzheimer’s disease need to be designed to minimise a stress response that may exacerbate brain pathology

Association between the serotonin transporter gene polymorphism and verbal learning in older adults is moderated by gender

The S allele of the functional 5-HTTLPR polymorphism has previously been associated with reductions in memory function. Giventhe change in function of the serotonergic system in older adults, and the functional consequences of memory decline in this agegroup, further investigation into the impact of 5-HTTLPR in healthy older adults is required. This investigation examined the effectof 5-HTTLPR variants (S carriers versus L/L homozygotes) on verbal and visual episodic memory in 438 healthy older adultsparticipating in the Tasmanian Healthy Brain Project (age range 50–79 years, M= 60.35, s.d. = 6.75). Direct effects of HTTLPR onmemory processes, in addition to indirect effects through interaction with age and gender, were assessed. Although no directeffects of 5-HTTLPR on memory processes were identified, our results indicated that gender significantly moderated the impact that5-HTTLPR variants exerted on the relationship between age and verbal episodic memory function as assessed by the Rey AuditoryVerbal Learning Test. No significant direct or indirect effects were identified in relation to visual memory performance. Overall, thisinvestigation found evidence to suggest that 5-HTTLPR genotype affects the association of age and verbal episodic memory formales and females differently, with the predicted negative effect of S carriage present in males but not females. Such findingsindicate a gender-dependent role for 5-HTTLPR in the verbal episodic memory system of healthy older adults

Selecting patients for randomized trials: a systematic approach based on risk group

BACKGROUND: A key aspect of randomized trial design is the choice of risk group. Some trials include patients from the entire at-risk population, others accrue only patients deemed to be at increased risk. We present a simple statistical approach for choosing between these approaches. The method is easily adapted to determine which of several competing definitions of high risk is optimal. METHOD: We treat eligibility criteria for a trial, such as a smoking history, as a prediction rule associated with a certain sensitivity (the number of patients who have the event and who are classified as high risk divided by the total number patients who have an event) and specificity (the number of patients who do not have an event and who do not meet criteria for high risk divided by the total number of patients who do not have an event). We then derive simple formulae to determine the proportion of patients receiving intervention, and the proportion who experience an event, where either all patients or only those at high risk are treated. We assume that the relative risk associated with intervention is the same over all choices of risk group. The proportion of events and interventions are combined using a net benefit approach and net benefit compared between strategies. RESULTS: We applied our method to design a trial of adjuvant therapy after prostatectomy. We were able to demonstrate that treating a high risk group was superior to treating all patients; choose the optimal definition of high risk; test the robustness of our results by sensitivity analysis. Our results had a ready clinical interpretation that could immediately aid trial design. CONCLUSION: The choice of risk group in randomized trials is usually based on rather informal methods. Our simple method demonstrates that this decision can be informed by simple statistical analyses