Sex hormones’ and menstrual cycle’s effects on cognitive performance remain unclear. This study examined cognitive differences between women across menstrual cycle phases, sex differences between women and men, and hormone–cognition associations. In total, 71 healthy young adults, aged 20–36 (42 women, 29 men), completed standardised cognitive tests measuring attention, processing speed, working memory, and visuospatial abilities. Women were tested twice: during menstrual (low-oestradiol) and pre-ovulatory (high-oestradiol) phases; men once. Hormone levels (oestradiol, progesterone, testosterone) were measured in blood samples via electrochemiluminescence immunoassay (ECLIA). Two analytical strategies were used: (1) within-subject analysis comparing women between phases, and (2) between-group comparison across three groups—women in menstrual phase, pre-ovulatory phase, and men. Women performed better during pre-ovulatory versus menstrual phase in working memory (Digit span forward: p = 0.04; Digit span backwards max: p = 0.02) and attention switching (Trail Making Test B: p = 0.01). Sex differences in processing speed were observed only during the menstrual phase (Trail Making Test A: p = 0.03; Stroop B: p = 0.04), but not in the pre-ovulatory phase. Positive correlations between oestradiol/progesterone and cognitive performance were found in men, while complex bidirectional relationships emerged in women during the menstrual phase only. Testosterone showed no significant correlations. These findings highlight hormonal status effects on cognitive sex differences.

Individuals with stroke often face cognitive and emotional challenges. Mindfulness-based stress reduction (MBSR), physical exercise (PE), and computerized cognitive training (CCT) are promising approaches to incorporate into post-stroke rehabilitation. To determine whether adding MBSR or PE to CCT improves cognition and mental health more than CCT alone, and whether any benefits are mediated by gains in mindfulness or fitness. The MindFit Project was a single-blind, parallel, 3-arm randomized controlled trial enrolling participants with chronic stroke, assigned to MBSR+CCT, PE+CCT, or CCT-only (1:1:1). All 12-week, home-based interventions were delivered online, with 5 sessions per week. The primary outcomes included 3 cognitive and 2 mental health measures; mindfulness and physical fitness were also assessed. Analyses used per-protocol and intention-to-treat approaches. A total of 141 individuals (mean [SD] age 57.7 [11.2] years; 40 % women) were randomly assigned to 3 groups (47 each). Participants were 28.54 (20.35) months post-stroke with a mean modified Rankin Scale score of 2.23 (1.04). Of these, 78 % (39 in MBSR+CCT, 34 in PE+CCT, and 37 in CCT-only) achieved an adherence rate of ≥80 % and were included in the per-protocol analysis. No significant between-group differences were found in primary outcomes (all P > 0.05). For secondary outcomes, the PE+CCT group showed significantly greater gains in leg strength than the others (F = 7.50, adjusted P = 0.009). These results were consistent with the intention-to-treat analysis. In the per-protocol sample, improvements in mindfulness significantly mediated emotional outcomes in the MBSR+CCT group (B = -1.08; 95 % bootstrapped CI, -2.77 to -0.01). In participants with predominantly mild chronic post-stroke deficits, adding MBSR or PE to CCT did not improve primary cognitive or emotional outcomes beyond CCT alone. However, PE+CCT increased fitness, and MBSR+CCT yielded mindfulness-mediated emotional gains. Future studies involving larger and more severe stroke samples are needed. NCT04759950 (www. gov).

Stroke survivors experience a wide range of physical, cognitive, and emotional challenges. In the MindFit Project, a randomized clinical trial, 141 chronic stroke patients were divided into three groups: mindfulness-based stress reduction (MBSR) with computerized cognitive training (CCT), physical exercise (PE) with CCT, and CCT alone. The interventions were conducted remotely over 12 weeks, including online group and individual sessions. This exploratory nested qualitative study aimed to investigate chronic stroke survivors' experiences, opinions, and perceived changes due to the interventions within the MindFit Project. The secondary objective was to describe the broader experience of their recovery journey. Twenty-seven participants were recruited through purposive sampling and engaged in semi-structured one-on-one interviews. Twelve received MBSR+CCT, nine received PE+CCT, and six received CCT-only. The interviews were recorded, transcribed, and analyzed using thematic analysis. Participants shared insights into their lives after stroke, including emotional and physical challenges, coping mechanisms, and the impact of societal perceptions. The interventions were generally positively valued, with MBSR aiding in emotional regulation, PE enhancing physical capabilities, and CCT improving cognition. The group setting provided valuable peer support and motivation, although some participants noted challenges owing to the heterogeneity. The telematic format was also appreciated for its accessibility, although it posed challenges to personal interaction and intervention supervision. Our study emphasizes the complexity of stroke recovery and the importance of holistic, patient-centered rehabilitation approaches. It also highlights the value of combining physical and non-physical interventions in a group setting, along with the potential of remote platforms to enhance the accessibility of rehabilitation programs. These findings generate hypotheses for future randomized clinical trials aimed at improving post-stroke recovery interventions.

Background/Objectives: Stroke often leads to persistent cognitive and emotional impairments, which rehabilitation may mitigate. However, the biological mechanisms underlying such improvements remain unclear. This study investigated whether supplementing computerized cognitive training (CCT) with mindfulness-based stress reduction (MBSR) or physical exercise (PE) modulated biomarkers of neuroplasticity, inflammation, and stress in patients with chronic stroke compared to CCT alone. We also explored whether biomarker changes mediated or correlated with behavioral improvements. Methods: In a three-arm, single-blind, randomized controlled trial (NCT04759950), 141 patients with chronic stroke were randomized (1:1:1) to MBSR+CCT, PE+CCT, or CCT-only for 12 weeks. Plasma levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), C-reactive protein (CRP), interleukin-6 (IL-6), and cortisol were measured at baseline and post-intervention. Cognitive, mental health, mindfulness, and fitness outcomes were also assessed. Between- and within-group changes were analyzed using ANCOVA and paired t-tests. Per-protocol and complete-case analyses were conducted. Results: Among the 109 participants with ≥80% adherence, the only significant between-group difference was for VEGF: it remained stable in the MBSR+CCT group but declined in PE+CCT and CCT-only. Within-group analyses showed significant decreases in cortisol in MBSR+CCT and PE+CCT, while IGF-1 levels declined across all groups. In contrast, BDNF, IL-6, and CRP did not show significant changes, and biomarker changes were not significantly associated with behavioral improvements. Complete-case analysis (n = 126) yielded similar findings. Conclusions: Our findings suggest that combining MBSR or PE with CCT may modulate certain biological processes relevant to stroke recovery. MBSR may help maintain VEGF levels, which could support vascular health, while MBSR and PE may contribute to lowering cortisol levels. However, since no clear association with behavioral improvements was found, further research is needed to determine the clinical relevance of these biomarker changes in stroke recovery.

Evidence linking fitness components to cognition and brain structure in young adults is limited and mixed, yet early adulthood is a key life-course stage when health behaviors consolidate, potentially shaping later brain health. This exploratory study examines the relationship between physical fitness components, cognitive functioning, and brain volumes, investigating sex differences, and assessing whether brain volumes mediate the fitness-cognition relationship. This cross-sectional study included 94 university students (mean age 21.6 [2.1] years; 45 [47.9%] females). Fitness, cognitive, and brain volume measures were obtained. Multiple linear regression models examined associations between fitness components and cognitive and brain outcomes. Sex moderation was tested by adding sex-by-fitness interaction terms to the regression models, and mediation analyses examined whether brain volumes mediated fitness-cognition associations. In the total sample, higher cardiorespiratory fitness was associated with better processing speed and smaller cingulate cortex volume. Formal moderation analyses showed that sex significantly moderated the associations between flexibility and attention-speed and processing speed, with positive associations in males and negative or null associations in females. No significant sex moderation was observed for brain volumes. Brain volumes did not mediate the relationship between physical fitness components and cognitive outcomes. Different physical fitness components were associated with cognitive functions and brain volumes in young adults, and some associations-particularly those involving physical flexibility and attention/processing speed-varied by sex at birth. Brain volumes did not explain the observed fitness-cognition associations.

University students often experience high psychosocial stress and lifestyle irregularities that may affect hypothalamic-pituitary-adrenal axis regulation and epigenetic regulation of the glucocorticoid receptor gene (NR3C1). This study examined associations of lifestyle factors with peripheral NR3C1 DNA methylation and cortisol output, and their relationships with psychological distress and cognitive function. A cross-sectional study included 97 university students (48 women; mean age = 21.6 years). Salivary NR3C1 promoter methylation was measured by pyrosequencing, and two components (C1, C2) were derived. Salivary cortisol area under the curve with respect to ground (AUCg) was calculated. Lifestyle behaviors, cardiorespiratory fitness (CRF), symptoms of depression, anxiety, and stress, and cognitive domains were assessed. Multiple regression and moderation analyses tested associations and interactions with sex and BMI. In uncorrected analyses, higher sedentary behavior was associated with lower NR3C1 C2 scores, and higher physical activity and CRF were related to lower cortisol AUCg. Higher NR3C1 C1 scores were associated with poorer executive function and inhibition, and cortisol AUCg was positively associated with depressive symptoms. However, none of these associations survived correction for multiple comparisons. Exploratory analyses indicated that higher NR3C1 C2 scores were associated with better attention at lower BMI and better attention-processing speed in women, whereas higher NR3C1 C1 scores were associated with poorer inhibition in men. Nominal findings suggest movement-related behaviors as the clearest lifestyle correlates of stress-system markers. Moderation analyses suggest sex- and BMI-related heterogeneity in selected cognition-methylation associations. These findings require confirmation in adequately powered studies.