Strategies to Promote Cognitive Health in Aging: Recent Evidence and Innovations.

PURPOSE OF REVIEW: We review recent work on applications of non-pharmacologic strategies to promote cognitive health in older adulthood and discuss potential network mechanisms, limitations, and considerations for improving intervention uptake and efficacy. RECENT FINDINGS: In healthy older adults and patients with mild cognitive impairment, cognitive training produces global and domain-specific cognitive gains, though effect sizes tend to be modest and transfer is variable. Non-invasive brain stimulation has shown moderate success in enhancing cognitive function, though the optimum approach, parameters, and cortical targets require further investigation. Physical activity improves cognitive functions in late life, with emerging trials highlighting key intervention components that may maximize treatment outcomes. Multimodal interventions may be superior to single-component interventions in conferring cognitive gains, although interpretation is limited by modest sample sizes and variability in training components and parameters. Across modalities, individual differences in patient characteristics predict therapeutic response. These interventions may advance cognitive health by modulating functional networks that support core cognitive abilities including the default mode, executive control, and salience networks. Effectiveness of cognitive enhancement strategies may be increased with clinician-led coaching, booster sessions, gamification, integration of multiple intervention modalities, and concrete applications to everyday functioning. Future trials involving rigorous comparisons of training components, parameters, and delivery formats will be essential in establishing the precise approaches needed to maximize cognitive outcomes. Novel studies using patient-level clinical and neuroimaging features to predict individual differences in training gains may inform the development of personalized intervention prescriptions to optimize cognitive health in late life.

Genome-wide histone state profiling of fibroblasts from the opossum, Monodelphis domestica, identifies the first marsupial-specific imprinted gene.

BACKGROUND: Imprinted genes have been extensively documented in eutherian mammals and found to exhibit significant interspecific variation in the suites of genes that are imprinted and in their regulation between tissues and developmental stages. Much less is known about imprinted loci in metatherian (marsupial) mammals, wherein studies have been limited to a small number of genes previously known to be imprinted in eutherians. We describe the first ab initio search for imprinted marsupial genes, in fibroblasts from the opossum, Monodelphis domestica, based on a genome-wide ChIP-seq strategy to identify promoters that are simultaneously marked by mutually exclusive, transcriptionally opposing histone modifications. RESULTS: We identified a novel imprinted gene (Meis1) and two additional monoallelically expressed genes, one of which (Cstb) showed allele-specific, but non-imprinted expression. Imprinted vs. allele-specific expression could not be resolved for the third monoallelically expressed gene (Rpl17). Transcriptionally opposing histone modifications H3K4me3, H3K9Ac, and H3K9me3 were found at the promoters of all three genes, but differential DNA methylation was not detected at CpG islands at any of these promoters. CONCLUSIONS: In generating the first genome-wide histone modification profiles for a marsupial, we identified the first gene that is imprinted in a marsupial but not in eutherian mammals. This outcome demonstrates the practicality of an ab initio discovery strategy and implicates histone modification, but not differential DNA methylation, as a conserved mechanism for marking imprinted genes in all therian mammals. Our findings suggest that marsupials use multiple epigenetic mechanisms for imprinting and support the concept that lineage-specific selective forces can produce sets of imprinted genes that differ between metatherian and eutherian lines.