Depressive symptoms in cognitively unimpaired older adults are associated with lower structural and functional integrity in a frontolimbic network.

Subclinical depressive symptoms are associated with increased risk of Alzheimer's disease (AD), but the brain mechanisms underlying this relationship are still unclear. We aimed to provide a comprehensive overview of the brain substrates of subclinical depressive symptoms in cognitively unimpaired older adults using complementary multimodal neuroimaging data. We included cognitively unimpaired older adults from the baseline data of the primary cohort Age-Well (n = 135), and from the replication cohort ADNI (n = 252). In both cohorts, subclinical depressive symptoms were assessed using the 15-item version of the Geriatric Depression Scale; based on this scale, participants were classified as having depressive symptoms (>0) or not (0). Voxel-wise between-group comparisons were performed to highlight differences in gray matter volume, glucose metabolism and amyloid deposition; as well as white matter integrity (only available in Age-Well). Age-Well participants with subclinical depressive symptoms had lower gray matter volume in the hippocampus and lower white matter integrity in the fornix and the posterior parts of the cingulum and corpus callosum, compared to participants without symptoms. Hippocampal atrophy was recovered in ADNI, where participants with subclinical depressive symptoms also showed glucose hypometabolism in the hippocampus, amygdala, precuneus/posterior cingulate cortex, medial and dorsolateral prefrontal cortex, insula, and temporoparietal cortex. Subclinical depressive symptoms were not associated with brain amyloid deposition in either cohort. Subclinical depressive symptoms in ageing are linked with neurodegeneration biomarkers in the frontolimbic network including brain areas particularly sensitive to AD. The relationship between depressive symptoms and AD may be partly underpinned by neurodegeneration in common brain regions.

The Effect of Mindfulness-based Programs on Cognitive Function in Adults: A Systematic Review and Meta-analysis.

Mindfulness-based programs (MBPs) are increasingly utilized to improve mental health. Interest in the putative effects of MBPs on cognitive function is also growing. This is the first meta-analysis of objective cognitive outcomes across multiple domains from randomized MBP studies of adults. Seven databases were systematically searched to January 2020. Fifty-six unique studies (n = 2,931) were included, of which 45 (n = 2,238) were synthesized using robust variance estimation meta-analysis. Meta-regression and subgroup analyses evaluated moderators. Pooling data across cognitive domains, the summary effect size for all studies favored MBPs over comparators and was small in magnitude (g = 0.15; [0.05, 0.24]). Across subgroup analyses of individual cognitive domains/subdomains, MBPs outperformed comparators for executive function (g = 0.15; [0.02, 0.27]) and working memory outcomes (g = 0.23; [0.11, 0.36]) only. Subgroup analyses identified significant effects for studies of non-clinical samples, as well as for adults aged over 60. Across all studies, MBPs outperformed inactive, but not active comparators. Limitations include the primarily unclear within-study risk of bias (only a minority of studies were considered low risk), and that statistical constraints rendered some p-values unreliable. Together, results partially corroborate the hypothesized link between mindfulness practices and cognitive performance. This review was registered with PROSPERO [CRD42018100904].

Effects of a Mindfulness-Based Intervention versus Health Self-Management on Subclinical Anxiety in Older Adults with Subjective Cognitive Decline: The SCD-Well Randomized Superiority Trial.

INTRODUCTION: Older adults experiencing subjective cognitive decline (SCD) have a heightened risk of developing dementia and frequently experience subclinical anxiety, which is itself associated with dementia risk. OBJECTIVE: To understand whether subclinical anxiety symptoms in SCD can be reduced through behavioral interventions. METHODS: SCD-Well is a randomized controlled trial designed to determine whether an 8-week mindfulness-based intervention (caring mindfulness-based approach for seniors; CMBAS) is superior to a structurally matched health self-management program (HSMP) in reducing subclinical anxiety. Participants were recruited from memory clinics at 4 European sites. The primary outcome was change in anxiety symptoms (trait subscale of the State-Trait Anxiety Inventory; trait-STAI) from pre- to postintervention. Secondary outcomes included a change in state anxiety and depression symptoms postintervention and 6 months postrandomization (follow-up). RESULTS: One hundred forty-seven participants (mean [SD] age: 72.7 [6.9] years; 64.6% women; CMBAS, n = 73; HSMP, n = 74) were included in the intention-to-treat analysis. There was no difference in trait-STAI between groups postintervention (adjusted change difference: -1.25 points; 95% CI -4.76 to 2.25) or at follow-up (adjusted change difference: -0.43 points; 95% CI -2.92 to 2.07). Trait-STAI decreased postintervention in both groups (CMBAS: -3.43 points; 95% CI -5.27 to -1.59; HSMP: -2.29 points; 95% CI -4.14 to -0.44) and reductions were maintained at follow-up. No between-group differences were observed for change in state anxiety or depression symptoms. CONCLUSIONS: A time-limited mindfulness intervention is not superior to health self-management in reducing subclinical anxiety symptoms in SCD. The sustained reduction observed across both groups suggests that subclinical anxiety symptoms in SCD are modifiable. ClinicalTrials.gov identifier: NCT03005652.

Emotions in attacker-defender conflicts.

The distinction between attackers and defenders might help refine the understanding of the role of emotions in conflicts. Here, we briefly discuss differences between attackers and defenders in terms of appraisals, action tendencies, emotional preferences, and brain activities. Finally, we outline how attackers and defenders may differ in their response to emotion-based interventions that aim to promote conflict resolution.

Structural covariance networks of the dorsal anterior insula predict females' individual differences in empathic responding.

Previous functional imaging studies have shown key roles of the dorsal anterior insula (dAI) and anterior midcingulate cortex (aMCC) in empathy for the suffering of others. The current study mapped structural covariance networks of these regions and assessed the relationship between networks and individual differences in empathic responding in 94 females. Individual differences in empathy were assessed through average state measures in response to a video task showing others' suffering, and through questionnaire-based trait measures of empathic concern. Overall, covariance patterns indicated that dAI and aMCC are principal hubs within prefrontal, temporolimbic, and midline structural covariance networks. Importantly, participants with high empathy state ratings showed increased covariance of dAI, but not aMCC, to prefrontal and limbic brain regions. This relationship was specific for empathy and could not be explained by individual differences in negative affect ratings. Regarding questionnaire-based empathic trait measures, we observed a similar, albeit weaker modulation of dAI covariance, confirming the robustness of our findings. Our analysis, thus, provides novel evidence for a specific contribution of frontolimbic structural covariance networks to individual differences in social emotions beyond negative affect.

Functional neural plasticity and associated changes in positive affect after compassion training.

The development of social emotions such as compassion is crucial for successful social interactions as well as for the maintenance of mental and physical health, especially when confronted with distressing life events. Yet, the neural mechanisms supporting the training of these emotions are poorly understood. To study affective plasticity in healthy adults, we measured functional neural and subjective responses to witnessing the distress of others in a newly developed task (Socio-affective Video Task). Participants' initial empathic responses to the task were accompanied by negative affect and activations in the anterior insula and anterior medial cingulate cortex--a core neural network underlying empathy for pain. Whereas participants reacted with negative affect before training, compassion training increased positive affective experiences, even in response to witnessing others in distress. On the neural level, we observed that, compared with a memory control group, compassion training elicited activity in a neural network including the medial orbitofrontal cortex, putamen, pallidum, and ventral tegmental area--brain regions previously associated with positive affect and affiliation. Taken together, these findings suggest that the deliberate cultivation of compassion offers a new coping strategy that fosters positive affect even when confronted with the distress of others.

The evolution of subjective cognition after meditation training in older people: a secondary analysis of the three-arm age-well randomized controlled trial.

Aging is associated with cognitive changes, even in the absence of brain pathology. This study aimed to determine if meditation training, by comparison to active and passive control groups, is linked to changes in the perception of cognitive functioning in older adults. One hundred thirty-four healthy older participants from the Age-Well Randomized Clinical Trial were included: 45 followed a meditation training, 45 a non-native language training and 44 had no intervention. Subjective cognition was assessed at baseline and following the 18-month intervention period. Perception of attentional efficiency was assessed using internal and external Attentional Style Questionnaire (ASQ) subscale scores. Perception of global cognitive capacities was measured via the total score of Cognitive Difficulties Scale (CDS). Deltas ([posttest minus pretest scores]/standard deviation at pretest) were calculated for the analyses. Generalized mixed effects models controlling for age, sex, education and baseline scores revealed that meditation training decreased the vulnerability score toward external distractors measured by the ASQ compared to non-native language training. However, no between-groups differences on ASQ internal or CDS total scores were observed. Results suggest a beneficial effect of meditation practice on perceived management of external distracting information in daily life. Meditation training may cultivate the ability to focus on specific information (e.g., breath) and ignore stimulation from other kinds of stimuli (e.g., noise).

Impact of mindfulness-based and health self-management interventions on mindfulness, self-compassion, and physical activity in older adults with subjective cognitive decline: A secondary analysis of the SCD-Well randomized controlled trial.

INTRODUCTION: Older adults experiencing subjective cognitive decline (SCD) have a higher risk of dementia. Reducing this risk through behavioral interventions, which can increase emotional well-being (mindfulness and compassion) and physical activity, is crucial in SCD. METHODS: SCD-Well is a multicenter, observer-blind, randomized, controlled, superiority trial. Three hundred forty-seven participants (mean [standard deviation] age: 72.7 [6.9] years; 64.6% women) were recruited from memory clinics in four European sites to assess the impact of an 8-week caring mindfulness-based approach for seniors (CMBAS) and a health self-management program (HSMP) on mindfulness, self-compassion, and physical activity. RESULTS: CMBAS showed a significant within-group increase in self-compassion from baseline to post-intervention and both a within- and between-group increase to follow-up visit (24 weeks). HSMP showed a significant within- and between-group increase in physical activity from baseline to post-intervention and to follow-up visit. DISCUSSION: Non-pharmacological interventions can differentially promote modifiable factors linked to healthy aging in older adults with SCD.

Worry and ruminative brooding: associations with cognitive and physical health in older adults.

Introduction: Mental health conditions are associated with cognition and physical function in older adults. We examined whether worry and ruminative brooding, key symptoms of certain mental health conditions, are related to subjective and/or objective measures of cognitive and physical (cardiovascular) health. Methods: We used baseline data from 282 participants from the SCD-Well and Age-Well trials (178 female; agemean = 71.1 years). We measured worry and ruminative brooding using the Penn State Worry Questionnaire and the Ruminative Response Scale-brooding subscale. We assessed subjective physical health using the WHOQOL-Bref physical subscale, and objective physical health via blood pressure and modified versions of the Framingham Risk Score and Charlson Comorbidity Index. With subjective and objective cognition, we utilized the Cognitive Difficulties Scale and a global composite (modified Preclinical Alzheimer's Cognitive Composite, PACC5, with the Wechsler Adult Intelligence Scale-IV, category fluency, Mattis Dementia Rating Scale-2, and either the California Verbal Learning Test or the Rey Auditory Verbal Learning Test). We conducted linear regressions, adjusted for education, age, sex and cohort. Results: Worry and ruminative brooding were negatively associated with subjective physical health (worry: ß = -0.245, 95%CI -0.357 to -0.133, p < 0.001; ruminative brooding: ß = -0.224, 95%CI -0.334 to -0.113, p < 0.001) and subjective cognitive difficulties (worry: ß = 0.196, 95%CI 0.091 to 0.302, p < 0.001; ruminative brooding: ß = 0.239, 95%CI 0.133 to 0.346, p < 0.001). We did not observe associations between worry or ruminative brooding and any measure of objective health. Discussion: Worry and ruminative brooding may be common mechanisms associated with subjective but not objective health. Alternatively, cognitively unimpaired older adults may become aware of subtle changes not captured by objective measures used in this study. Interventions reducing worry and ruminative brooding may promote subjective physical and cognitive health; however, more research is needed to determine causality of the relationships.

Getting closer: compassion training increases feelings of closeness toward a disliked person.

Evidence-based interventions to favor more harmonious interactions in difficult relationships remain scarce. This study examined whether compassion training may have beneficial effects in an ongoing tense relationship with a disliked person, by reducing schadenfreude toward them and increasing felt interpersonal closeness. 108 participants were assigned to one of three 5-week trainings in a longitudinal randomized controlled study: compassion training, reappraisal training (emotion regulation control condition), or Italian language training (neutral active control condition). The disliked person was not targeted during the trainings to test potential transfer effects. Misfortune scenarios and a measure of interpersonal closeness were used to test whether schadenfreude and closeness feelings toward a disliked person changed from pre- to post-training, across different experimental and control groups. Only compassion and reappraisal trainees reported a decrease of schadenfreude feelings toward the disliked person compared to their pre-training ratings, no changes were observed in the Italian language training. Importantly, feelings of closeness toward the disliked person increased in the compassion training group compared to the other two groups. This increase of closeness feelings could be a central mechanism for improving social interactions. These transfer effects open new perspectives concerning emotion regulation interventions in conflict resolution.

Spreading positive change: Societal benefits of meditation.

Research over the past decades has revealed a variety of beneficial effects of meditation training. These beneficial effects span the levels of health and well-being, cognition, emotion, and social behavior. Around the same time, sociologists have shown that traits and outcomes on the individual level have the potential to spread in communities over three or more degrees. This means, for example, that changes can spread from one person to the next, and on to yet another person. Here, we propose that meditation-induced changes may likewise spread through the social networks of meditation practitioners. Such spreading may happen by positively influencing others through prosocial actions, improved cognitive functioning, and increased positive affect. Positive affective states and their underlying physiological correlates may also be shared in the literal sense. We argue that the spreading of positive meditation effects could provide the basis for collective responses to some of the urgent challenges we face in our current time and society and call for future meditation research to examine the phenomenon.

The effect of plasma cortisol on hippocampal atrophy and clinical progression in mild cognitive impairment.

Introduction: Both elevated cortisol and hippocampal volume have been linked to an increased risk for the development of Alzheimer's disease (AD). This longitudinal study assessed the effects of plasma cortisol on hippocampal atrophy and clinical progression rates in patients with mild cognitive impairment (MCI). Methods: Patients with amnestic MCI (n = 304) were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) based on availability of baseline plasma cortisol and hippocampal volume measures, assessed at baseline and during follow-ups. We investigated associations between plasma cortisol, hippocampal volume, and risk of clinical progression to AD over a study period of up to 100 months (mean follow-up time 36.8 months) using linear mixed models, Cox proportional hazards models, and Kaplan-Meier estimators. Results: Plasma cortisol predicted greater hippocampal atrophy, such that participants with higher cortisol showed faster decline in hippocampal volume over time (interaction: ß = -0.15, p = 0.004). Small hippocampal volume predicted a higher risk of clinical progression to AD (haard ratio [HR] = 2.15; confidence in terval [CI], 1.64-2.80; p < 0.001). A similar effect was not found for cortisol (HR = 1.206; CI, 0.82-1.37; p = 0.670) and there was no statistical evidence for an interaction between hippocampal volume and cortisol on clinical progression (HR = 0.81; CI, 0.57-0.17; p = 0.260). Discussion: Our findings suggest that higher cortisol predicts higher hippocampal atrophy, which in turn is a risk factor for progression to AD. Regulation of the hypothalamic-pituitary-adrenal axis through stress-reducing lifestyle interventions might be a protective factor against hippocampal degeneration at the prodromal stage of AD.

Situational assessment of empathy and compassion: Predicting prosociality using a video-based task.

Classical psychometric approaches in social science measure individuals' tendency to experience empathy and compassion. Using abstract questionnaire items, they place high demand on subjects' capacity to introspect, memorize, and generalize the corresponding emotions. We employed a Socio-affective Video Task (SoVT)-an alternative approach that measures situationally elicited emotions-and assessed its predictive power over prosocial behavior against classical questionnaires in a sample of Israeli university students. We characterized the conceptual embedding of the SoVT concerning other measures of prosocial affect and cognition, and tested group identification as an alternative precursor to prosocial behavior. Eighty participants rated their reactions to videos that presented the suffering of others or everyday scenes on scales of negative affect (providing a proxy for elicited empathy) and compassion. We then administered classical questionnaires that target empathy (the Interpersonal Reactivity Index) and compassion (the Compassionate Love Scale), as well as measures of hypothetical and real-life helping and prosocial attitudes-including conflict attitudes and intergroup bias. While compassion ratings in the SoVT failed to predict prosociality more accurately than classical questionnaires, the SoVT empathy index succeeded and correlated strongly with other precursors of prosociality. These results support video-based situational assessment as an implicit and robust alternative in the measurement of empathy-related processes.

The Effect of Meditation-Based Interventions on Patients with Fatigue Symptoms: A Systematic Review and Meta-Analysis.

Persistent fatigue constitutes a prevalent and debilitating symptom in several diseases. The symptom is not effectively alleviated by pharmaceutical treatments, and meditation has been proposed as a non-pharmacological intervention. Indeed, meditation has been shown to reduce inflammatory/immune problems, pain, stress, anxiety and depression which are associated with pathological fatigue. This review synthesizes data from randomized control trials (RCTs) that explored the effect of meditation-based interventions (MeBIs) on fatigue in pathological conditions. Eight databases were searched from inception to April 2020. Thirty-four RCTs met eligibility criteria and covered six conditions (68% cancer), 32 of which were included in the meta-analysis. The main analysis showed an effect in favor of MeBIs compared to control groups (g = 0.62). Separate moderator analyses assessing control group, pathological condition, and MeBI type, highlighted a significantly moderating role of the control group. Indeed, compared to actively controlled studies, studies using a passive control group were associated with a statistically significantly more beneficial impact of the MeBIs (g = 0.83). These results indicate that MeBIs alleviate pathological fatigue and it seems that the studies with a passive control group showed a greater effect of MeBI on the reduction of fatigue compared to studies using active control groups. However, the specific effect of meditation type and pathological condition should be analyzed with more studies, and there remains a need to assess meditation effects on different types of fatigue (i.e., physical and mental) and in additional conditions (e.g., post-COVID-19).

An 18-month meditation training selectively improves psychological well-being in older adults: A secondary analysis of a randomised controlled trial.

OBJECTIVES: As the world population is ageing, it is vital to understand how older adults can maintain and deepen their psychological well-being as they are confronted with the unique challenges of ageing in a complex world. Theoretical work has highlighted the promising role of intentional mental training such as meditation practice for enhancing human flourishing. However, meditation-based randomised controlled trials in older adults are lacking. We aimed to investigate the effects of meditation training on psychological well-being in older adults. METHODS: This study presents a secondary analysis of the Age-Well trial (ClinicalTrials.gov: NCT02977819), which randomised 137 healthy older adults (age range: 65 to 84 years) to an 18-month meditation training, an active comparator (English language training), or a passive control. Well-being was measured at baseline, mid-intervention, and 18-month post-randomisation using the Psychological Well-being Scale (PWBS), the World Health Organisation's Quality of Life (QoL) Assessment psychological subscale, and composite scores reflecting the meditation-based well-being dimensions of awareness, connection, insight, and a global score comprising the average of these meditation-based dimensions. RESULTS: The 18-month meditation training was superior to English training on changes in the global score (0.54 [95% CI: 0.26, 0.82], p = 0.0002) and the subscales of awareness, connection, insight, and superior to no-intervention only on changes in the global score (0.54 [95% CI: 0.26, 0.82], p = 0.0002) and awareness. Between-group differences in psychological QoL in favour of meditation did not remain significant after adjusting for multiple comparisons. There were no between-group differences in PWBS total score. Within the meditation group, psychological QoL, awareness, insight, and the global score increased significantly from baseline to 18-month post-randomisation. CONCLUSION: The longest randomised meditation training conducted to date enhanced a global composite score reflecting the meditation-based well-being dimensions of awareness, connection, and insight in older adults. Future research is needed to delineate the cognitive, affective, and behavioural factors that predict responsiveness to meditation and thus help refine the development of tailored meditation training.

A multicenter feasibility study on implementing a brief mindful breathing exercise into regular university courses.

Practicing mindfulness is associated with stress reduction and with positive effects in the context of learning and teaching. Although effects on student populations have been studied extensively, there are few studies implementing mindfulness exercises in university courses directly. For this reason, we aimed to investigate whether the use of a brief mindfulness exercise in regular university courses, guided by the lecturers, is feasible and has immediate effects on the students' mental states. We conducted a preregistered multicenter study with one observational arm, following an ABAB design. In total, N = 325 students from 19 different university courses were included at baseline and n = 101 students at post measurement. Students were recruited by N = 14 lecturers located in six different universities in Germany. Lecturers started their courses either by guiding a brief mindfulness exercise (intervention condition) or as they regularly would, with no such exercise (control condition). In both conditions, the mental states of students and lecturers were assessed. Over the semester, n = 1193 weekly observations from students and n = 160 observations from lecturers were collected. Intervention effects were analyzed with linear mixed-effects models. The brief mindfulness exercise, compared to no such exercise, was associated with lower stress composite scores, higher presence composite scores, higher motivation for the courses, as well as better mood in students. Effects persisted throughout a respective course session. Lecturers also reported positive effects of instructing mindfulness. Implementing a brief mindfulness exercise in regular university teaching sessions is feasible and has positive effects on both students and lecturers.

Exposure to negative socio-emotional events induces sustained alteration of resting-state brain networks in older adults.

Basic emotional functions seem well preserved in older adults. However, their reactivity to and recovery from socially negative events remain poorly characterized. To address this, we designed a 'task-rest' paradigm in which 182 participants from two independent experiments underwent functional magnetic resonance imaging while exposed to socio-emotional videos. Experiment 1 (N = 55) validated the task in young and older participants and unveiled age-dependent effects on brain activity and connectivity that predominated in resting periods after (rather than during) negative social scenes. Crucially, emotional elicitation potentiated subsequent resting-state connectivity between default mode network and amygdala exclusively in older adults. Experiment 2 replicated these results in a large older adult cohort (N = 127) and additionally showed that emotion-driven changes in posterior default mode network-amygdala connectivity were associated with anxiety, rumination and negative thoughts. These findings uncover the neural dynamics of empathy-related functions in older adults and help understand its relationship to poor social stress recovery.

Effects of a mindfulness-based intervention and a health self-management programme on psychological well-being in older adults with subjective cognitive decline: Secondary analyses from the SCD-Well randomised clinical trial.

OBJECTIVES: Older adults with subjective cognitive decline (SCD) recruited from memory clinics have an increased risk of developing dementia and regularly experience reduced psychological well-being related to memory concerns and fear of dementia. Research on improving well-being in SCD is limited and lacks non-pharmacological approaches. We investigated whether mindfulness-based and health education interventions can enhance well-being in SCD. METHODS: The SCD-Well trial (ClinicalTrials.gov: NCT03005652) randomised 147 older adults with SCD to an 8-week caring mindfulness-based approach for seniors (CMBAS) or an active comparator (health self-management programme [HSMP]). Well-being was assessed at baseline, post-intervention, and 6-month post-randomisation using the Psychological Well-being Scale (PWBS), the World Health Organisation's Quality of Life (QoL) Assessment psychological subscale, and composites capturing meditation-based well-being dimensions of awareness, connection, and insight. Mixed effects models were used to assess between- and within-group differences in change. RESULTS: CMBAS was superior to HSMP on changes in connection at post-intervention. Within both groups, PWBS total scores, psychological QoL, and composite scores did not increase. Exploratory analyses indicated increases in PWBS autonomy at post-intervention in both groups. CONCLUSION: Two non-pharmacological interventions were associated with only limited effects on psychological well-being in SCD. Longer intervention studies with waitlist/retest control groups are needed to assess if our findings reflect intervention brevity and/or minimal base rate changes in well-being.

Effects of Meditation Training and Non-Native Language Training on Cognition in Older Adults: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Nonpharmacological interventions are a potential strategy to maintain or promote cognitive functioning in older adults. Objective: To investigate the effects of 18 months' meditation training and 18 months' non-native language training on cognition in older adults. Design, Setting, and Participants: This study was a secondary analysis of the Age-Well trial, an 18-month, observer-masked, randomized clinical trial with 3 parallel arms. Eligible participants were community-dwelling adults aged 65 years and older residing in Caen, France. Participants were enrolled from November 24, 2016, to March 5, 2018, and randomly assigned (1:1:1) to meditation training, non-native language (English) training, or no intervention arms. Final follow-up was completed on February 6, 2020. Data were analyzed between December 2021 and November 2022. Interventions: The 18-month meditation and non-native language training interventions were structurally equivalent and included 2-hour weekly group sessions, daily home practice of 20 minutes or longer, and 1 day of more intensive home practice. The no intervention group was instructed not to change their habits and to continue living as usual. Main Outcomes and Measures: Cognition (a prespecified secondary outcome of the Age-Well trial) was assessed preintervention and postintervention via the Preclinical Alzheimer Cognitive Composite 5 (PACC5), and composites assessing episodic memory, executive function, and attention. Results: Among 137 randomized participants, 2 were excluded for not meeting eligibility criteria, leaving 135 (mean [SD] age, 69.3 [3.8] years; 83 female [61%]) eligible for analysis. One participant among the remaining 135 did not complete the trial. In adjusted mixed effects models, no interaction effects were observed between visit and group for PACC5 (F2,131.39 = 2.58; P = .08), episodic memory (F2,131.60 = 2.34; P = .10), executive function (F2,131.26 = 0.89; P = .41), or attention (F2,131.20 = 0.34; P = .79). Results remained substantively unchanged across sensitivity and exploratory analyses. Conclusions and Relevance: In this secondary analysis of an 18-month randomized trial, meditation and non-native language training did not confer salutary cognitive effects. Although further analyses are needed to explore the effects of these interventions on other relevant outcomes related to aging and well-being, these findings did not support the use of these interventions for enhancing cognition in cognitively healthy older adults. Trial Registration: ClinicalTrials.gov Identifier: NCT02977819.

Long-term environmental enrichment is associated with better fornix microstructure in older adults.

Background: Sustained environmental enrichment (EE) through a variety of leisure activities may decrease the risk of developing Alzheimer's disease. This cross-sectional cohort study investigated the association between long-term EE in young adulthood through middle life and microstructure of fiber tracts associated with the memory system in older adults. Methods: N = 201 cognitively unimpaired participants (≥ 60 years of age) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) baseline cohort were included. Two groups of participants with higher (n = 104) or lower (n = 97) long-term EE were identified, using the self-reported frequency of diverse physical, intellectual, and social leisure activities between the ages 13 to 65. White matter (WM) microstructure was measured by fractional anisotropy (FA) and mean diffusivity (MD) in the fornix, uncinate fasciculus, and parahippocampal cingulum using diffusion tensor imaging. Long-term EE groups (lower/higher) were compared with adjustment for potential confounders, such as education, crystallized intelligence, and socio-economic status. Results: Reported participation in higher long-term EE was associated with greater fornix microstructure, as indicated by higher FA (standardized ß = 0.117, p = 0.033) and lower MD (ß = -0.147, p = 0.015). Greater fornix microstructure was indirectly associated (FA: unstandardized B = 0.619, p = 0.038; MD: B = -0.035, p = 0.026) with better memory function through higher long-term EE. No significant effects were found for the other WM tracts. Conclusion: Our findings suggest that sustained participation in a greater variety of leisure activities relates to preserved WM microstructure in the memory system in older adults. This could be facilitated by the multimodal stimulation associated with the engagement in a physically, intellectually, and socially enriched lifestyle. Longitudinal studies will be needed to support this assumption.