The COVID-19 pandemic significantly challenged mental health of populations worldwide. We aimed to assess changes in mental health of cognitively unimpaired (CU) older adults with pre-existing subclinical depressive symptoms during pandemic-related confinements, and the factors that could modulate these changes. CU older adults with (DepS, n = 53) and without (NoDepS, n = 47) pre-existing subclinical depressive symptoms (defined using the Geriatric Depression Scale at baseline) from the Age-Well randomized controlled trial (NCT02977819) were included - for whom data at baseline, post-intervention visits and during the two national confinements were available. The 18-month meditation or non-native language training intervention was completed before the pandemic. DepS, compared to NoDepS, had higher levels of depressive and anxiety symptoms at all assessments, including confinements. DepS had a greater increase in anxiety than NoDepS between the two confinements, and this increase was associated with greater ruminative brooding at baseline, but was not moderated by the meditation training intervention or by meditation practice during confinements. Pre-existing subclinical depressive symptoms in older adults contribute to mental health deterioration during confinements, with rumination being the main factor involved - stressing the need to treat these symptoms.

The COVID-19 pandemic significantly challenged mental health of populations worldwide. We aimed to assess changes in mental health of cognitively unimpaired (CU) older adults with pre-existing subclinical depressive symptoms during pandemic-related confinements, and the factors that could modulate these changes. CU older adults with (DepS, n=53) and without (NoDepS, n=47) pre-existing subclinical depressive symptoms (defined using the Geriatric Depression Scale at baseline) from the Age-Well randomized controlled trial (NCT02977819) were included – for whom data at baseline, post-intervention visits and during the two national confinements were available. The 18-month meditation or non-native language training intervention was completed before the pandemic. DepS, compared to NoDepS, had higher levels of depressive and anxiety symptoms at all assessments, including confinements. DepS had a greater increase in anxiety than NoDepS between the two confinements, and this increase was associated with greater ruminative brooding at baseline, but was not moderated by meditation practice. Pre-existing subclinical depressive symptoms in older adults contribute to mental health deterioration during confinements, with rumination being the main factor involved – stressing the need to treat these symptoms.

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. 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’. 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. 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.

Sleep, especially slow wave sleep (SWS), is essential for cognitive functioning and is reduced in aging. The impact of sleep quality on cognition is variable, especially in aging. Cognitive reserve (CR) may be an important modulator of these effects. We aimed at investigating this question to better identify individuals in whom sleep disturbances might have greater behavioral consequences. Polysomnography and neuropsychological assessments were performed in 135 cognitively intact older adults (mean age ± SD: 69.4 ± 3.8y) from the Age-Well randomized controlled trial (baseline data). Two measures of cognitive engagement throughout life were used as CR proxies. Linear regression analyses were performed between the proportion of SWS, and executive function and episodic memory composite scores. Then, interaction analyses between SWS and CR proxies on cognition were conducted to assess the possible impact of CR on these links. SWS was positively associated with episodic memory, but not with executive function. CR proxies modulated the associations between SWS and both executive and episodic memory performance. Specifically, individuals with higher CR were able to maintain cognitive performance despite low amounts of SWS. This study provides the first evidence that CR may protect against the deleterious effects of age-related sleep changes on cognition.

ImportanceNonpharmacological interventions are a potential strategy to maintain or promote cognitive functioning in older adults.ObjectiveTo investigate the effects of 18 months’ meditation training and 18 months’ non-native language training on cognition in older adults.Design, Setting, and ParticipantsThis 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.InterventionsThe 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 MeasuresCognition (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.ResultsAmong 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 RelevanceIn 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 RegistrationClinicalTrials.gov Identifier: NCT02977819

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 MeasuresCognition (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 (F-2,F-131.39=2.58; P=.08), episodic memory (F-2,F-131.60=2.34; P=.10), executive function (F-2,F-131.26=0.89; P=.41), or attention (F-2,F-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 RegistrationClinicalTrials.gov Identifier: NCT02977819

Background Older individuals with subjective cognitive decline (SCD) perceive that their cognition has declined but do not show objective impairment on neuropsychological tests. Individuals with SCD are at elevated risk of objective cognitive decline and incident dementia. Non-pharmacological interventions (including mindfulness-based and health self-management approaches) are a potential strategy to maintain or improve cognition in SCD, which may ultimately reduce dementia risk. Methods This study utilized data from the SCD-Well randomized controlled trial. One hundred forty-seven older adults with SCD ( M Age = 72.7 years; 64% female) were recruited from memory clinics in four European countries and randomized to one of two group-based, 8-week interventions: a Caring Mindfulness-based Approach for Seniors (CMBAS) or a health self-management program (HSMP). Participants were assessed at baseline, post-intervention (week 8), and at 6-month follow-up (week 24) using a range of cognitive tests. From these tests, three composites were derived—an “abridged” Preclinical Alzheimer’s Cognitive Composite 5 (PACC5 Abridged ), an attention composite, and an executive function composite. Both per-protocol and intention-to-treat analyses were performed. Linear mixed models evaluated the change in outcomes between and within arms and adjusted for covariates and cognitive retest effects. Sensitivity models repeated the per-protocol analyses for participants who attended ≥ 4 intervention sessions. Results Across all cognitive composites, there were no significant time-by-trial arm interactions and no measurable cognitive retest effects; sensitivity analyses supported these results. Improvements, however, were observed within both trial arms on the PACC5 Abridged from baseline to follow-up (Δ [95% confidence interval]: CMBAS = 0.34 [0.19, 0.48]; HSMP = 0.30 [0.15, 0.44]). There was weaker evidence of an improvement in attention but no effects on executive function. Conclusions Two non-pharmacological interventions conferred small, non-differing improvements to a global cognitive composite sensitive to amyloid-beta-related decline. There was weaker evidence of an effect on attention, and no evidence of an effect on executive function. Importantly, observed improvements were maintained beyond the end of the interventions. Improving cognition is an important step toward dementia prevention, and future research is needed to delineate the mechanisms of action of these interventions and to utilize clinical endpoints (i.e., progression to mild cognitive impairment or dementia). Trial registration ClinicalTrials.gov, NCT03005652.

BACKGROUND:As the population ages, maintaining mental health and well-being of older adults is a public health priority. Beyond objective measures of health, self-perceived quality of life (QoL) is a good indicator of successful aging. In older adults, it has been shown that QoL is related to structural brain changes. However, QoL is a multi-faceted concept and little is known about the specific relationship of each QoL domain to brain structure, nor about the links with other aspects of brain integrity, including white matter microstructure, brain perfusion and amyloid deposition, which are particularly relevant in aging. Therefore, we aimed to better characterize the brain biomarkers associated with each QoL domain using a comprehensive multimodal neuroimaging approach in older adults.METHODS:One hundred and thirty-five cognitively unimpaired older adults (mean age ± SD: 69.4 ± 3.8 y) underwent structural and diffusion magnetic resonance imaging, together with early and late florbetapir positron emission tomography scans. QoL was assessed using the brief version of the World Health Organization's QoL instrument, which allows measuring four distinct domains of QoL: self-perceived physical health, psychological health, social relationships and environment. Multiple regression analyses were carried out to identify the independent global neuroimaging predictor(s) of each QoL domain, and voxel-wise analyses were then conducted with the significant predictor(s) to highlight the brain regions involved. Age, sex, education and the other QoL domains were entered as covariates in these analyses. Finally, forward stepwise multiple regressions were conducted to determine the specific items of the relevant QoL domain(s) that contributed the most to these brain associations.RESULTS:Only physical health QoL was associated with global neuroimaging values, specifically gray matter volume and white matter mean kurtosis, with higher physical health QoL being associated with greater brain integrity. These relationships were still significant after correction for objective physical health and physical activity measures. No association was found with global brain perfusion or global amyloid deposition. Voxel-wise analyses revealed that the relationships with physical health QoL concerned the anterior insula and ventrolateral prefrontal cortex, and the corpus callosum, corona radiata, inferior frontal white matter and cingulum. Self-perceived daily living activities and self-perceived pain and discomfort were the items that contributed the most to these associations with gray matter volume and white matter mean kurtosis, respectively.CONCLUSIONS:Better self-perceived physical health, encompassing daily living activities and pain and discomfort, was the only QoL domain related to brain structural integrity including higher global gray matter volume and global white matter microstructural integrity in cognitively unimpaired older adults. The relationships involved brain structures belonging to the salience network, the pain pathway and the empathy network. While previous studies showed a link between objective measures of physical health, our findings specifically highlight the relevance of monitoring and promoting self-perceived physical health in the older population. Longitudinal studies are needed to assess the direction and causality of the relationships between QoL and brain integrity.

Sleep, especially slow wave sleep (SWS), favors efficient cognitive functioning. This effect may be impaired in aging, but might be modulated by cognitive reserve. Indeed, a study reported that highly educated older adults were able to better tolerate the negative effects of subjective sleep disturbances on verbal fluency scores. Growing evidence also suggests that sleep may favor amyloid clearance. In this context, we investigated the effect of cognitive reserve and amyloid deposition on the links between SWS and cognitive performance in older adults.

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. 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 (PACC5 Abridged ). Linear mixed models estimated the change in outcome measures (the PACC5 Abridged 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. There was a statistically significant improvement in the PACC5 Abridged in both arms of the trial ( p <.001), which did not differ between groups. The mean change in PACC5 Abridged 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 PACC5 Abridged was non-significant, ruling out retest effects as a substantive explanation for results. Amongst the PACC5 Abridged constituent tests, significant improvement was observed in the RAVLT and WAIS-IV Coding. 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.

The COVID-19 pandemic and the associated distancing measures dramatically affect psychoaffective health, and this is accentuated in older adults who are more vulnerable to the situation. In this study, we are interested in the predictors of emotional resilience in healthy older adults, and also on how the repetition of confinement periods could influence this resilience and its predictors. 102 cognitively unimpaired older adults from the Age-Well cohort were included. They all completed the Depression Anxiety Stress Scales (DASS-42) during each period of national confinement (April and November 2020), used here as a measure of emotional resilience (lower scores indicating greater resilience). Baseline measures from the Age-Well study, all acquired before the pandemic, were used as predictors, including demographics (age, sex, education), personality (Big Five Inventory), psychological (anxiety [STAI-B], depression [GDS]), lifestyle (Lifetime of experience questionnaire), global cognitive functioning (Mattis-DRS) and neuroimaging data (hippocampal volume, brain perfusion, amyloid burden). We ran stepwise regressions to predict emotional resilience during the first confinement. Then, we used paired t-test to assess the evolution of emotional resilience between the two confinements. Finally, we replicated the stepwise regressions to predict changes in resilience over time ('second-minus-first' confinement). Neuroticism was the only significant predictor of the DASS-42 score during the first confinement (β=.48; p<.001; Figure-1), lower neuroticism being associated with better resilience. We found the DASS-42 score to increase significantly from the first to the second confinement, indicating decreased emotional resilience over time. Moreover, higher neuroticism (β=.53; p<.001) and higher agreeableness (β=.20; p=.03) were associated with higher DASS-42 increase over time (Figure-2). Our study suggests that lower neuroticism is the main predictor of greater emotional resilience to the COVID-19-related confinement. Importantly, the repetition of the confinement situation is associated with a decrease in emotional resilience in older adults, especially if they are prone to experience distress (neuroticism) or have a particularly social personality (agreeableness). Overall, these results underline the increasing need, as the crisis persists, for a psychoaffective support of older adult.

AbstractBackgroundWhite matter hyperintensities (WMH) are frequent in the older adults and are associated to worse cognitive performances and to dementia. Alzheimer’s disease is associated with greater brain WMH volume, particularly in posterior regions, compared to cognitively unimpaired older adults. The aim of this study was to assess in details the topography of brain WMH and their links with cognition in amyloid‐positive cognitively impaired older adults, i.e. patients in the Alzheimer’s continuum (ALZ), compared to amyloid‐negative cognitively unimpaired adults (controls).MethodFifty‐four ALZ and forty controls matched for age and cardiovascular risk factors were included in the IMAP cohort (Caen, France). Amyloid status was based on Florbetapir PET scans. In addition, each participant underwent 1) brain structural T1 and FLAIR MRI scans used for the automatic segmentation of WMH in the frontal, parietal, temporal, occipital lobes and in the corpus callosum (CC) region and subregions; 2) a comprehensive neuropsychological assessment of global cognition, episodic memory, working memory and executive functions. The regional volumes of WMH were compared between groups and the relationship of regional WMH to cognition was assessed within the ALZ patients.ResultWMH volumes were significantly higher in ALZ patients than in controls in all brain regions, with highest differences in the splenium of the CC (p= 0.00005, size effect r = 0.42) and lowest effects in the frontal lobe (p = 0.025, size effect r = 0.23) (Figure 1). Within the ALZ patient group, WMH volumes of the CC, particularly in the splenium, were negatively associated with global cognition, working memory and executive functions (Figure 2). Total and frontal WMH volumes were also negatively associated with working memory, but this relationship did not survive correction for multiple comparisons.ConclusionWMH in the splenium of the CC most specifically characterize amyloid‐positive patients in the Alzheimer’s continuum and correlate to worse cognition especially in frontal cognitive functions. These specific ALZ‐related WMH are probably not only due to small vessel disease and could be secondary to neurodegenerescence.