The impact of deep space radiation on cognitive performance: From biological sex to biomarkers to countermeasures.

In the coming decade, astronauts will travel back to the moon in preparation for future Mars missions. Exposure to galactic cosmic radiation (GCR) is a major obstacle for deep space travel. Using multivariate principal components analysis, we found sex-dimorphic responses in mice exposed to accelerated charged particles to simulate GCR (GCRsim); males displayed impaired spatial learning, whereas females did not. Mechanistically, these GCRsim-induced learning impairments corresponded with chronic microglia activation and synaptic alterations in the hippocampus. Temporary microglia depletion shortly after GCRsim exposure mitigated GCRsim-induced deficits measured months after the radiation exposure. Furthermore, blood monocyte levels measured early after GCRsim exposure were predictive of the late learning deficits and microglia activation measured in the male mice. Our findings (i) advance our understanding of charged particle­induced cognitive challenges, (ii) provide evidence for early peripheral biomarkers for identifying late cognitive deficits, and (iii) offer potential therapeutic strategies for mitigating GCR-induced cognitive loss.

Small molecule cognitive enhancer reverses age-related memory decline in mice.

With increased life expectancy, age-associated cognitive decline becomes a growing concern, even in the absence of recognizable neurodegenerative disease. The integrated stress response (ISR) is activated during aging and contributes to age-related brain phenotypes. We demonstrate that treatment with the drug-like small-molecule ISR inhibitor ISRIB reverses ISR activation in the brain, as indicated by decreased levels of activating transcription factor 4 (ATF4) and phosphorylated eukaryotic translation initiation factor eIF2. Furthermore, ISRIB treatment reverses spatial memory deficits and ameliorates working memory in old mice. At the cellular level in the hippocampus, ISR inhibition (i) rescues intrinsic neuronal electrophysiological properties, (ii) restores spine density and (iii) reduces immune profiles, specifically interferon and T cell-mediated responses. Thus, pharmacological interference with the ISR emerges as a promising intervention strategy for combating age-related cognitive decline in otherwise healthy individuals.

Family-centered depression treatment for older men in primary care: a qualitative study of stakeholder perspectives.

BACKGROUND: Family members often play important roles in the lives of depressed older men and frequently attend primary care visits with their loved ones, yet surprisingly little is known about how to most effectively engage and include family members in depression treatment. However, including family in depression treatment may be difficult due to several factors, such as depression stigma and family conflicts. The objective of this study was to describe challenges in engaging family members in older men's depression treatment and potential strategies to overcome those challenges. METHODS: A cross-sectional, qualitative descriptive interview study was conducted in a safety-net, Federally Qualified Health Center in California's Central Valley. A total of 37 stakeholders were recruited, including 15 depressed older (i.e. age ≥ 60) men, 12 family members, and 10 clinic staff. Depressed men were identified through mail outreach, waiting room screening, and referral. Depressed men identified family members who were later approached to participate. We also recruited a purposeful sample of clinic staff. Interviews explored stakeholder perspectives on family involvement in men's depression treatment as part of a primary care intervention. Interviews were conducted using a semi-structured interview guide, tape-recorded, transcribed verbatim, and translated if the interview was conducted in Spanish. RESULTS: Four themes were identified representing core challenges: engaging men at the right time; preserving men's sense of autonomy; managing privacy concerns; and navigating family tensions. Stakeholders also provided practical suggestions and advice about how each of these challenges might be addressed. CONCLUSIONS: While engaging family is a promising approach to strengthen depression care for older men in primary care settings, several potential challenges exist. Family- centered depression intervention development and clinical practice need to anticipate these challenges and to develop approaches and guidelines to address them.