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

Effect of an 18-Month Meditation Training on Regional Brain Volume and Perfusion in Older Adults: The Age-Well Randomized Clinical Trial.

peer reviewedImportance: No lifestyle-based randomized clinical trial directly targets psychoaffective risk factors of dementia. Meditation practices recently emerged as a promising mental training exercise to foster brain health and reduce dementia risk. Objective: To investigate the effects of meditation training on brain integrity in older adults. Design, Setting, and Participants: Age-Well was a randomized, controlled superiority trial with blinded end point assessment. Community-dwelling cognitively unimpaired adults 65 years and older were enrolled between November 24, 2016, and March 5, 2018, in France. Participants were randomly assigned (1:1:1) to (1) an 18-month meditation-based training, (2) a structurally matched non-native language (English) training, or (3) no intervention arm. Analysis took place between December 2020 and October 2021. Interventions: Meditation and non-native language training included 2-hour weekly group sessions, practice of 20 minutes or longer daily at home, and 1-day intensive practices. Main Outcomes and Measures: Primary outcomes included volume and perfusion of anterior cingulate cortex (ACC) and insula. Main secondary outcomes included a global composite score capturing metacognitive, prosocial, and self-regulatory capacities and constituent subscores. Results: Among 137 participants (mean [SD] age, 69.4 [3.8] years; 83 [60.6%] female; 54 [39.4%] male) assigned to the meditation (n = 45), non-native language training (n = 46), or no intervention (n = 46) groups, all but 1 completed the trial. There were no differences in volume changes of ACC (0.01 [98.75% CI, -0.02 to 0.05]; P = .36) or insula (0.01 [98.75% CI, -0.02 to 0.03]; P = .58) between meditation and no intervention or non-native language training groups, respectively. Differences in perfusion changes did not reach statistical significance for meditation compared with no intervention in ACC (0.02 [98.75% CI, -0.01 to 0.05]; P = .06) or compared with non-native language training in insula (0.02 [98.75% CI, -0.01 to 0.05]; P = .09). Meditation was superior to non-native language training on 18-month changes in a global composite score capturing attention regulation, socioemotional, and self-knowledge capacities (Cohen d, 0.52 [95% CI, 0.19-0.85]; P = .002). Conclusions and Relevance: The study findings confirm the feasibility of meditation and non-native language training in elderly individuals, with high adherence and very low attrition. Findings also show positive behavioral effects of meditation that were not reflected on volume, and not significantly on perfusion, of target brain areas. Trial Registration: ClinicalTrials.gov Identifier: NCT02977819

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Motivations and willingness of general practitioners in France to participate in primary care research as investigators

International audienceBackgroundClinical research is mostly conducted among hospitalized patients, which restricts the generalizability of research results. The involvement of GPs in research has been consistently highlighted as a factor associated with successful study recruitment.ObjectivesTo assess GPs’ motivations and willingness to participate in primary care research as investigators and to identify factors associated with their willingness.MethodsWe conducted an observational, cross-sectional study in Normandy, France, with a self-questionnaire sent to 3002 GPs. We collected data on GPs’ socio-demographic characteristics, their experiences and their expectations regarding research, and their reasons for non-participation.ResultsOverall, 489 questionnaires were collected. Two hundred and forty-six GPs (50.3%) were interested in participating in clinical research as investigators. The two main conditions for participation as investigators were the relevance of the study topic for clinical practice (80.5%) and the feedback of study results (80.1%). The two main reasons for non-participation were lack of time (79.4%) and administrative burden (43.6%). Age between 27 and 34 years (adjusted odds ratio [AOR] = 2.86, P = 0.004) and GP trainer status (AOR = 2.41, P < 0.001) were associated with willingness to participate in primary care research. Age between 60 and 70 years (AOR = 0.53, P = 0.03) and locum status (AOR = 0.40, P = 0.04) were associated with non-participation in research.ConclusionsBased on our results, we were able to establish a profile of GPs willing to participate in primary care research as investigators. GPs’ involvement should be based on their preferred areas of research. Different incentives such as a dedicated clinical research nurse or financial support could also be considered

Role of Cardiovascular Risk Factors on the Association Between Physical Activity and Brain Integrity Markers in Older Adults

International audienceBackground and Objectives Physical activity has been associated with a decreased risk for dementia, but the mechanisms underlying this association remain to be determined. Our objective was to assess whether cardiovascular risk factors mediate the association between physical activity and brain integrity markers in older adults. Methods At baseline, participants from the Age-Well study completed a physical activity questionnaire and underwent cardiovascular risk factors collection (systolic blood pressure, body mass index [BMI], current smoker status, and high-density lipoprotein cholesterol, total cholesterol, and insulin levels) and multimodal neuroimaging (structural MRI, diffusion MRI, FDG-PET, and florbetapir PET). Multiple regressions were conducted to assess the association among physical activity, cardiovascular risk factors, and neuroimaging. Mediation analyses were performed to test whether cardiovascular risk factors mediated the associations between physical activity and neuroimaging. Results A total of 134 cognitively unimpaired older adults (≥65 years) were included. Higher physical activity was associated with higher gray matter (GM) volume (β = 0.174, p = 0.030) and cerebral glucose metabolism (β = 0.247, p = 0.019) but not with amyloid deposition or white matter integrity. Higher physical activity was associated with lower insulin level and BMI but not with the other cardiovascular risk factors. Lower insulin level and BMI were related to higher GM volume but not to cerebral glucose metabolism. When controlling for insulin level and BMI, the association between physical activity and cerebral glucose metabolism remained unchanged, while the association with GM volume was lost. When insulin level and BMI were entered in the same model, only BMI remained a significant predictor of GM volume. Mediation analyses confirmed that insulin level and BMI mediated the association between physical activity and GM volume. Analyses were replicated within Alzheimer disease–sensitive regions and results remained overall similar. Discussion The association between physical activity and GM volume is mediated by changes in insulin level and BMI. In contrast, the association with cerebral glucose metabolism seems to be independent from cardiovascular risk factors. Older adults engaging in physical activity experience cardiovascular benefits through the maintenance of a lower BMI and insulin level, resulting in greater structural brain integrity. This study has implications for understanding how physical activity affects brain health and may help in developing strategies to prevent or delay age-related decline. Trial Registration Information EudraCT: 2016-002,441-36; IDRCB: 2016-A01767-44; ClinicalTrials.gov Identifier: NCT02977819

White matter hyperintensities across the adult life span: Links with age, amyloid load and cognition

poster presentationInternational audienceBackground: Brain white matter hyperintensities (WMH) are frequent in older adults, including cognitively unimpaired individuals and are associated to decreased cognitive performances. The prevalence of WMH and their links with cognitive performance and with cortical β-amyloid (Aβ) burden have been rarely assessed in younger adults. The aim of this study was to assess the impact of WMH in younger and older cognitively unimpaired adults on cognitive performances and the possible interaction with cortical β-amyloid (Aβ) burden. Method: Two hundred and seventy-two cognitively unimpaired adults from the community (from the IMAP study and the Age-Well trial) were enrolled and age-stratified in 86 younger adults (YA; ≤60 years old) and 187 older adults (OA; >60 years old). All participants underwent i) a comprehensive neuropsychological assessment allowing to obtain composite scores of episodic memory, processing speed, working memory, executive functions, and global cognition; ii) brain structural T1 and FLAIR MRI scans used for automatic segmentation of WMH volumes; and iii) a Florbetapir-PET scan to measure cortical Aβ. Within each group, the relationships of total and regional WMH to age and cognition were assessed, as well as the impact of cortical Aβ on these relationships. Result: WMH increased with age in both groups but more sharply in OA than YA, particularly in the parietal lobe. Higher WMH volume was associated to worse cognitive performances in both groups. Particularly, working memory, processing speed and global cognition were negatively associated with global and regional WMH in YA and executive functions were negatively associated to occipital WMH in OA. Cortical Aβ differentially impacts the links between WMH and cognition in YA versus OA. Conclusion: WMH volume increases with age and is negatively associated to cognitive performances including in YA. This study argues for the clinical relevance of WMH even in middle age

White matter hyperintensities across the adult lifespan: relation to age, Aβ load, and cognition

International audienceAbstract Background White matter hyperintensities (WMH) are very frequent in older adults and associated with worse cognitive performance. Little is known about the links between WMH and vascular risk factors, cortical β-amyloid (Aβ) load, and cognition in cognitively unimpaired adults across the entire lifespan, especially in young and middle-aged adults. Methods One hundred and thirty-seven cognitively unimpaired adults from the community were enrolled (IMAP cohort). Participants underwent (i) a comprehensive neuropsychological assessment of episodic memory, processing speed, working memory, and executive functions; (ii) brain structural T1 and FLAIR MRI scans used for the automatic segmentation of total and regional (frontal, parietal, temporal, occipital, and corpus callosum) WMH; and (iii) a Florbetapir-PET scan to measure cortical Aβ. The relationships of total and regional WMH to age, vascular risk factors, cortical Aβ, and cognition were assessed within the whole sample, but also splitting the sample in two age groups (≤ or > 60 years old). Results WMH increased with age across the adult lifespan, i.e., even in young and middle-aged adults. Systolic blood pressure, diastolic blood pressure, and glycated hemoglobin were all associated with higher WMH before, but not after, adjusting for age and the other vascular risk factors. Higher frontal, temporal, and occipital WMH were associated with greater Aβ, but this association was no longer significant when adjusting for age and vascular risk factors. Higher total and frontal WMH were associated with worse performance in executive functions, with no interactive effect of the age group. In contrast, there was a significant interaction of the age group on the link between WMH and working memory, which was significant within the subgroup of young/middle-aged adults only. Adding cortical Aβ load in the models did not alter the results, and there was no interaction between WMH and Aβ on cognition. Conclusion WMH increased with age and were associated with worse executive functions across the adult lifespan and with worse working memory in young/middle-aged adults. Aβ load was weakly associated with WMH and did not change the relationship found between WMH and executive functions. This study argues for the clinical relevance of WMH across the adult lifespan, even in young and middle-aged adults with low WMH

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

Impact on disease mortality of clinical, biological, and virological characteristics at hospital admission and overtime in COVID‐19 patients

International audienc