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Background: Non‐pharmacological interventions are a potential strategy to maintain or promote cognitive functioning in older adults. We investigated the effects of 18‐months meditation or non‐native language training versus no intervention on cognition in older adults. Method: Age‐Well was an observer‐blind, randomised, controlled clinical trial with three parallel arms. Cognitively healthy adults aged ≥ 65 years and were recruited in France. Participants were randomised (1:1:1) to a meditation training, non‐native language (English) training, or a no intervention group for 18 months. Cognition (a pre‐specified secondary outcome) was assessed pre‐ and post‐intervention via the Preclinical Alzheimer's Cognitive Composite 5 (PACC5), and composites assessing episodic memory, executive function, and attention. Linear mixed models, adjusted for age, sex, and education, evaluated cognitive changes between arms. Baseline neocortical amyloid deposition was added as a fixed effect in a sensitivity analysis. Additional sensitivity analyses assessed intervention effects for participants who attended at least 20% of intervention classes or were classified as 'responders'. Results: 137 participants were randomly assigned to meditation training (n = 45), non‐native language training (n = 46), or no intervention (n = 46). Two participants were excluded for not meeting eligibility criteria, and one died during follow‐up (Figure 1). A positive effect of non‐native language training was observed on episodic memory relative to the no intervention group (0·32 [95% CI: 0·04‐0·61], p = 0·025), and on PACC5 scores compared to meditation training (0·33 [95% CI: 0·01‐0·66], p = 0·045; Figure 2). In sensitivity analyses, neither the inclusion of amyloid as an additional covariate nor the exclusion of participants who attended <20% of intervention classes affected results. Following exclusion of 'non‐responders', evidence for beneficial effects (relative to the no intervention group) on episodic memory became significant for meditation training (0·33 [0·01, 0·66]), and was weakened for non‐native language training (0·30 [‐0·02, 0·62]). No other between‐group differences emerged. Conclusion: Among cognitively healthy older adults, there was limited evidence for positive effects of 18‐months meditation training on cognition. However, in addition to having real‐life utility, non‐native language learning in late life may have beneficial effects on cognitive domains affected early in Alzheimer's disease. Studies investigating whether these effects are long‐lasting are warranted. [ABSTRACT FROM AUTHOR]

Background: Positive and negative psychological factors represent pertinent moderators of relative risk and protection for cognitive decline and dementia. For example, repetitive negative thinking has been associated with accelerated cognitive decline and AD pathology1, whereas self‐reflection and purpose in life have been related to better cognition and cognitive resilience2,3. Existing studies predominately focus on individual factors, thus it is unknown whether psychological profiles, combining risk and protective features, are differentially associated with cognitive function. Method: Individuals without objective cognitive impairment were included from two European studies: the middle‐aged Barcelona Brain Health Initiative (N = 741)4 and the older‐adult Medit‐Ageing (N = 279)5,6 cohorts. Self‐report questionnaires to assess levels of psychological risk and protective factors were completed and global cognitive assessments obtained in both studies (Table 1). Latent Profile Analysis (LPA) was performed on psychological questionnaire data to identify statistically different groups of individuals in each cohort separately. ANCOVA (adjusting for age, sex, and education), were then conducted to compare different psychological profiles according to cognitive status. Result: LPA identified a three‐class solution in both cohorts (Table 1 and Figure 1): "low levels of psychological protective factors" (class‐1), "high levels of psychological risk factors" (class‐2), and "average levels of psychological risk and protective factors" (class‐3). In both cohorts, psychological profile membership was significantly associated with cognition. Specifically, individuals with low levels of psychological protective factors had worse global cognitive function compared with individuals with other profiles (BBHI: F:6.05, p<0.002; Medit‐Ageing: F:7.99, p<0.001; Figure 2). Conclusion: Individual psychological risk and protective factors aggregated into three identifiable psychological profiles that were evident across two independent cohorts. In both cohorts, having a psychological profile with low levels of protective factors rather than high levels of risk factors, was associated with worse global cognitive function. Such observations may have implications for future, more personalized, application of psychological therapies contributing to dementia prevention. [ABSTRACT FROM AUTHOR]

Background: Recent evidence in Alzheimer's diseases suggests that early dysfunction of emotional processing may precede the onset of cognitive decline and dementia. Altered functional brain connectivity patterns also occur along with other brain changes many years before clinical AD symptoms. Method: We combined baseline multimodal neuroimaging data from cognitively healthy older adults (N = 125) enrolled in the Age‐Well trial of the Medit‐Ageing study. The aim was to elucidate the relationship of five AD risk factors (amyloid‐beta depositions and hypoperfusion with AV45‐PET, hippocampal atrophy, cognition with PACC‐5, cardiovascular risk with CAIDE) with carry‐over effects of social emotions and related brain functions. Using k‐means clustering analysis with the AD risk factors, we first defined participants with higher or lower preclinical risk for AD. We then used functional Magnetic Resonance Imaging to probe functional brain connectivity in resting periods following negative socio‐emotional videos in the SoVT‐Rest paradigm. Result: Participants with a higher preclinical AD risk showed reduced positivity bias in affect ratings and reduced connectivity patterns between control‐related frontal brain regions and emotion‐related limbic regions (amygdala). In particular, this fronto‐limbic connectivity was associated with higher cardiovascular risk on the CAIDE composite score. Conclusion: We find evidence for changes in post‐emotion functional recovery patterns in fronto‐limbic brain networks in at‐risk individuals for AD. These changes might reflect impaired emotion regulation processes. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive decline (SCD) denotes self‐reported cognitive concerns in the absence of objective cognitive impairment. Individuals with SCD convert to dementia at twice the annual rate of healthy controls, with relatively poorer cognition in SCD conferring additional risk. Non‐pharmacological interventions are currently undergoing intensive evaluation for promoting cognitive function in SCD. Method: This study utilized data from the SCD‐Well randomized controlled trial. One hundred forty‐seven older adults with SCD, recruited from clinics in four European countries, were randomized to one of two 8‐week non‐pharmacological interventions: the Caring Mindfulness‐Based Approach for Seniors (CMBAS), or a Health Self‐Management Program (HSMP). Participants' objective cognitive performance was assessed at baseline, post‐intervention, and 24‐weeks follow‐up using a battery of tests. Four of these (RAVLT, WAIS‐IV Coding, Mattis DRS‐2 and Category Fluency) were combined to yield an abridged version of the Preclinical Alzheimer's Cognitive Composite 5 (PACC5Abridged). Linear mixed models estimated the change in outcome measures (the PACC5Abridged and its constituents) within and between arms. All models were adjusted for country and participant demographics (sex, age, and education), as well as the time‐varying effect of participants' repeated practice with the outcome measures. Result: There was a statistically significant improvement in the PACC5Abridged in both arms of the trial (p<.001), which did not differ between groups. The mean change in PACC5Abridged from baseline to 24‐weeks was 0.28 for CMBAS, and 0.22 for HSMP (pooled baseline SD 0.72). The effect of participants' repeated practice on the PACC5Abridged was non‐significant, ruling out retest effects as a substantive explanation for results. Amongst the PACC5Abridged constituent tests, significant improvement was observed in the RAVLT and WAIS‐IV Coding. Conclusion: This clinical trial evaluated the effect of two 8‐week non‐pharmacological interventions on objective cognitive performance in SCD. Scores on a composite measure of early Alzheimer's disease related cognitive dysfunction improved in both arms, even after accounting for practice effects. These results paralleled those of the primary outcome measure (trait anxiety), for which scores also improved in both arms. This work adds to the growing body of evidence that non‐pharmacological interventions can impact cognition in individuals at increased risk of dementia. [ABSTRACT FROM AUTHOR]

Background: Self‐reflection is conceptualised as an introspective process that involves active evaluation of one's thoughts, feelings and behaviours. Engagement in self‐reflection is thought to yield more adaptive stress responses, that in turn result in better short‐term (e.g., reduced inflammatory responses to stressors) and long‐term (e.g., recovery from major depression) outcomes. Despite self‐reflection's known protective effect against adverse health outcomes, the association between self‐reflection and Alzheimer's disease (AD) risk is unknown. Method: Baseline data from 134 healthy older adults (mean age=69.3) enrolled in the Age‐Well clinical trial and 125 older adults with subjective cognitive decline (mean age=72.5) from the SCD‐Well clinical trial were included. All participants completed an assessment of self‐reflection. Modified versions of the Preclinical Alzheimer's Cognitive Composite 5 were used to measure global cognition in both cohorts. Additionally, in Age‐Well, glucose metabolism and amyloid deposition were assessed with PET scans, and the Lifestyle‐for‐Brain‐Health (LIBRA) AD‐risk index computed to assess health and lifestyle behaviours. Separate linear regressions were run to determine associations between self‐reflection levels and AD markers (i.e., global cognition, glucose metabolism, and amyloid deposition). Analyses adjusted for available prognostic characteristics associated with AD (e.g., age, sex, education and APOE4 status) and levels of psychological distress (i.e., depression and rumination). Furthermore, to explore the potential mechanism linking self‐reflection with AD markers, the relationship between self‐reflection and LIBRA scores was investigated. Result: Self‐reflection was positively associated with global cognition in both cohorts (Age‐Well: β=0.18, p=0.023; SCD‐Well: β=0.20, p=0.024) and glucose metabolism (Age‐Well: β=0.29, p=0.027; see Figure). No relationship, however, was found with amyloid deposition (Age‐Well: β=0.13, p=0.198). Self‐reflection was associated with LIBRA scores (Age‐Well: β=‐0.31, p=0.002), with lower self‐reflection levels associated with poorer health and lifestyle behaviours. Conclusion: Self‐reflection was associated with higher glucose metabolism, and with better global cognition in two independent older adult cohorts. For the first time, we introduce preliminary support for self‐reflection as a potential protective factor against AD‐related decline. Furthermore, the results suggest that self‐reflection may affect AD risk by influencing health and lifestyle behaviours. Both Age‐Well and SCD‐Well are clinical trials. Future work will investigate whether modifying self‐reflection via interventions affects AD markers. [ABSTRACT FROM AUTHOR]

Background: Subclinical depressive symptoms are prevalent in older adults. They are associated with increased risk for both clinical depression and Alzheimer's disease (AD), and may at least partly reflect early AD manifestations. However, the brain mechanisms underlying the relationship between depressive symptoms and AD remain to be elucidated. The aim of this study was to provide a comprehensive overview of the brain substrates of subclinical depressive symptoms in cognitively unimpaired older adults using complementary multimodal neuroimaging data in two independent cohorts. Method: We selected 135 cognitively unimpaired older adults from the baseline data of the primary cohort Age‐Well, and 252 from the replication cohort ADNI. In both cohorts, subclinical depressive symptoms were assessed using the 15‐item version of the Geriatric Depression Scale (GDS); based on this scale, participants were classified as having depressive symptoms (DepS; GDS > 0) or not (NoDepS; GDS = 0). Voxelwise between‐group comparisons were performed to highlight differences in gray matter volume and amyloid deposition (both cohorts), as well as white matter integrity, brain perfusion (Age‐Well) and glucose metabolism (ADNI). Analyses were corrected for age, sex and education (and anxiety when available i.e. in Age‐Well) and thresholded at p<0.005. Result: Older adults with subclinical depressive symptoms had significantly lower gray matter volume, perfusion and glucose metabolism in the hippocampus compared to participants without symptoms (Fig. 1). Glucose hypometabolism extended to the amygdala, precuneus/posterior cingulate and medial prefrontal cortex, insula, and temporoparietal cortex. Older adults with subclinical depressive symptoms also showed lower white matter integrity in the fornix and the posterior parts of the cingulum and corpus callosum. Brain amyloid deposition was not associated with the presence of subclinical depressive symptoms in either cohort. Conclusion: The presence of subclinical depressive symptoms in cognitively unimpaired older adults are associated with brain structural and functional changes in regions of the limbic network known to be particularly vulnerable to AD. Structural and functional changes overlapped in the hippocampus, indicating that deterioration in this region could underlie the relationship between depressive symptoms and AD while amyloid deposition does not appear to be involved at this stage. [ABSTRACT FROM AUTHOR]

Background: Subjectively experienced cognitive decline (SCD), particularly associated with worries, in older adults is known to be a risk factor for dementia. So far, only few studies focus on gender‐specific profiles in SCD. Method: Gender differences in SCD subjects who were enrolled in the SCD‐Well trial were analyzed with regard to their perception of subjective cognitive difficulties and the corresponding objective cognitive performance. SCD‐Well is a multicenter, observer‐blinded, randomized, and controlled superiority trial (Marchant et al. 2018). Two different types of 8‐week interventions are compared within the study: a mindfulness‐ and compassion‐based intervention with a validated health education program. 147 participants (95 female) were included. Data from the SCD‐Interview (SCD‐I; Miebach et al., 2019), the Cognitive Difficulties Scale (CDS; McNair & Kahn, 1983), and different cognitive scales summarized in a modified Preclinical Alzheimer's Cognitive Composite (PACC; Donohue et al., 2014) were analyzed for gender differences. Result: Statistical analyses revealed no gender differences concerning variables of the SCD‐I and CDS. Regarding objective cognitive performance, a significant gender effect for the PACC score with men showing lower cognitive performance was detected (U = 1859.00 , p <.05). However, only women showed a negative correlation between the PACC and reported SCD as indicated on the SCD‐I (r=‐.436, p= <.001) and CDS (r = ‐.514, p <.001): more subjective cognitive difficulties and worries were associated with lower cognitive performance. To further explore this relationship, we will analyse differences between sites. Conclusion: Literature reveals gender differences in SCD for objective cognition, neuroimaging and biomarkers (Wang & Tian, 2018). The present study supports the finding of woman performing better in a cognitive assessment than men. Moreover, it adds to this literature by showing an association between self‐perceived cognitive difficulties and actual cognitive performance in women, but not men. Further research is needed to provide a deeper understanding of gender differences in SCD, which are highly relevant for approaches on early detection of cognitive decline, which might in turn impact the choice of pre‐clinical interventions. [ABSTRACT FROM AUTHOR]

Background: The primary focus of mindfulness‐based program (MBP) research to date has been on mental health. More recently, attention has turned to putative effects on cognition. An evidence synthesis is required to answer the key question of 'Do MBPs confer cognitive benefit, and if so, for whom?' A particularly crucial distinction is whether benefits differ according to individuals' age. We undertook a systematic review and meta‐analysis of all relevant research across the adult lifespan. Method: This review was conducted according to PRISMA guidelines, registered on Prospero (#CRD42018100904), and conducted searches of 7 databases. Included studies must have used a group‐based MBP, randomized participants to conditions, and used objective cognitive outcome measures. Two independent researchers assessed studies against criteria, extracted data and rated study quality. Meta‐analyses used robust variance estimation to assess overall effects. Result: Forty‐six studies were included in the systematic review, and 38 contributed effect sizes for meta‐analysis (see figure). Across the studies included in the meta‐analysis, the cognitive domains most frequently assayed were executive function (66 outcomes) and attention (60 outcomes). All outcome measures were pooled for analysis. The studies of working‐age adults (18‐65 years old; k=28) included healthy, psychiatric and neurological samples (k=16 passively controlled studies; k=12 actively controlled studies). Studies of older adults (>65 years old; k=10) included healthy persons, and patients with subjective and objective cognitive impairment (k=7 passively controlled studies; k=3 actively controlled studies). When combining healthy and clinical studies of working‐age adults, meta‐analysis yielded a non‐significant pooled effect of MBP participation on cognitive performance compared to control conditions (g=0.28, p=.14; see table). A significant pooled effect was observed for the studies featuring older adults (g=0.27, p<.05; see table). Conclusion: The current review assessed the effects of MBPs relative to control conditions on cognitive performance in adults across the lifespan, and found evidence of a significant positive effect for older adults only. No evidence of a benefit for younger populations was identified. As research in this fast‐developing field continues, it will be possible to examine whether effects vary according to healthy or clinical status, and to establish whether specific cognitive domains are differentially impacted. [ABSTRACT FROM AUTHOR]

Background: Reflective pondering is an introspective mechanism conceptualised as actively seeking a solution to one's problems. Literature has consistently demonstrated positive associations between reflective pondering and improved mental health outcomes in clinical populations. Given that poor mental health (e.g. depression, anxiety) has been associated with increased dementia risk, and that reflective pondering improves mental health, we asked whether reflective pondering could also act as a protective factor against dementia, measured by cognitive function, in older adults. Method: Baseline data from 145 older adults with subjective cognitive decline (SCD; mean age = 72.2) from the SCD‐Well clinical trial and 135 healthy older adults (mean age = 70.5) from the Age‐Well clinical trial were included in this study. All participants completed the reflective pondering subscale of the Rumination Response Scale and a modified version of the Preclinical Alzheimer's Cognitive Composite (PACC; Donohue et al., 2014). Linear regressions were run to determine the association between reflective pondering and PACC scores in each cohort independently. Analyses controlled for available prognostic characteristics known to be associated with Alzheimer's disease (e.g. age, sex, education, depressive symptoms and APOE genotype). Result: In SCD‐Well reflective pondering was positively associated with PACC scores after controlling for age, sex, education and depressive symptoms (β = 0.05, p <.01), with higher levels of reflective pondering associated with better cognition. Similarly, in Age‐Well reflective pondering was also positively associated with PACC scores (β = 0.04, p =.03) aftercontrolling for age, sex, education, depressive symptoms and APOE genotype. Conclusion: In two independent cohorts that included healthy older adults and individuals with SCD, levels of reflective pondering were positively associated with a global cognitive marker of Alzheimer's risk. Our results introduce preliminary support for reflective pondering as a protective factor for cognitive function. Both SCD‐Well and Age‐Well are clinical trials, thus future work will evaluate the association between changes in reflective pondering due to intervention and cognitive function. [ABSTRACT FROM AUTHOR]