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Abstract This research explores different methodologies to modulate the effects of drowsiness on functional connectivity (FC) during resting-state functional magnetic resonance imaging (RS-fMRI). The study utilized a cohort of students (MRi-Share) and classified individuals into drowsy, alert, and mixed/undetermined states based on observed respiratory oscillations. We analyzed the FC group difference between drowsy and alert individuals after five different processing methods: the reference method, two based on physiological and a global signal regression of the BOLD time series signal, and two based on Gaussian standardizations of the FC distribution. According to the reference method, drowsy individuals exhibit higher cortico-cortical FC than alert individuals. First, we demonstrated that each method reduced the differences between drowsy and alert states. The second result is that the global signal regression was quantitively the most effective, minimizing significant FC differences to only 3.3% of the total FCs. However, one should consider the risks of overcorrection often associated with this methodology. Therefore, choosing a less aggressive form of regression, such as the physiological method or Gaussian-based approaches, might be a more cautious approach. Third and last, using the Gaussian-based methods, cortico-subcortical and intra-default mode network (DMN) FCs were significantly greater in alert than drowsy subjects. These findings bear resemblance to the anticipated patterns during the onset of sleep, where the cortex isolates itself to assist in transitioning into deeper slow wave sleep phases, simultaneously disconnecting the DMN.

Abstract Background The closure of bars and lockdowns related to the Covid-19 pandemic changed alcohol use levels in France during the spring of 2020. We wondered whether this sudden cessation of social interactions impacted students more than non-students and what factors specific to students would explain the increase in alcohol misuse. The aims of this study were to compare self-reported changes in alcohol misuse (alcohol intake and binge-drinking frequency) during the first Covid-19 lockdown from March 17 to May 10, 2020, between French students and non-students and describe factors associated with this alcohol misuse in each subgroup. Methods Data collected in the Confins study from April 8 to May 10, 2020, were used in cross-sectional analyses stratified by student status. Multiple logistic regression was performed to estimate the association between self-reported increase in alcohol intake or binge-drinking frequency (at least six drinks of alcohol on one occasion) and demographic, socioeconomic, and clinical factors, as well as conditions associated with the Covid-19 pandemic. The population-attributable fraction was then used to estimate the contribution of identified risk factors to increased alcohol misuse in students and non-students. Results Among both students and non-students, a self-reported decrease or no change in alcohol intake or binge-drinking was more common than an increase. However, the risk factors explaining an increase in alcohol intake differed among students (≥ 25 years old, not working or studying in the health field, and having suicidal ideation during the last 7 days) and non-students (having a medical diagnosis of mental disorders). The risk factors explaining an increase in binge-drinking frequency were similar in the two subgroups (being a tobacco smoker before lockdown and not practicing any physical activity during the last 7 days), except suicidal thoughts, which was a risk factor for alcohol misuse specific to students. Conclusions These results highlight the vulnerability of certain French students to alcohol misuse and the necessity of combining both mental health and substance use-related screening in the student population.

Abstract Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p

Blood pressure variability (BPV) impacts brain health by influencing brain structure and cerebrovascular pathologies, though the mechanisms are poorly understood. Changes in the cerebrovasculature may lead to late-onset depression, cognitive impairment, and dementia, however the relationship between BPV with depression and anxiety remains unclear, due to methodological differences and inconsistencies in past research. This review aims to clarify the association between BPV with depression and anxiety in adults to inform understandings of the mechanisms implicating BPV in cognitive health. A systematic search from inception through to January 2024 was performed on Embase, PubMed, PsycINFO, and Web of Science. Studies that assessed BPV quantified by beat-to-beat, 24-hour, or visit-to-visit were eligible if the standardised assessment of depression and/or anxiety were reported as a linear association, or mean differences across control and affect groups. A total of 14 articles reporting on 13 samples and N = 5055 persons met the inclusion criteria (median female proportion = 61 %, range 0 % - 76 %). A meta-analysis was not possible due to methodological heterogeneity in BPV measurements and metrics across studies. Mixed results were observed across depression studies with inconsistencies and variation in the direction, strength of association, and BPV metric. There was weak evidence from only three studies to support a linear association between systolic coefficient of variation and anxiety. Collectively, the findings contribute to understanding the association between BPV and brain health, suggesting that any relationship between BPV and brain structures critical for cognitive function are independent of depression and only modestly implicate anxiety.

BackgroundLittle is known about e-cigarette use in French students. Our aims were to estimate the prevalence of e-cigarette experimentation and current e-cigarette use; describe the reasons for using e-cigarettes; explore the vaping experience and identify the profiles of e-cigarette users.MethodsWe used a sequential, explanatory mixed methods design in a sample of French college students. Quantitative data was collected online for a cross-sectional analysis among 1698 students. Two separate analysis based on the thematic analysis and the Grounded Theory were also performed in 20 semi-structured interviews, focusing former and current smokers also current vapers.ResultsThe prevalence of e-cigarette experimentation was 39.3% (95% CI: 35.2-44.0) and 5.1% (95% CI: 3.2-8.0) of students were current e-cigarette users. Experimentation was opportunistic while current usage was rational, requiring to acquire a personal electronic device, getting used to its technicality, appreciating its availability, discretion, and learning the practice. In this context, three distinct groups of e-cigarette users were identified, based on assumed identity, tobacco and e-cigarette use, the functions assigned to e-cigarettes, and intentions with regards to vaping in the future.ConclusionDespite some limitations mainly related to the participants self-selection, this research showed that while many smokers and former smokers have tried e-cigarettes in this student population, few have continued to use them continuously. Moreover, these current e-cigarette users were a heterogeneous group. Longitudinal studies are needed in young adult smokers for a better understanding of how their tobacco and e-cigarette use affect each other and change over time.

Abstract Restrictive measures during the COVID-19 epidemic have led to increased levels of loneliness, especially among university students, although the influence on suicidal thoughts remains unclear. In this cross-sectional study of 1913 French university students, those with the highest level of loneliness had a fourfold increased risk of suicidal thoughts. Perceived loneliness should be incorporated into suicide risk assessment, and assistance in coping with loneliness should be considered as a means of reducing suicidal risk in vulnerable groups, like university students.

BackgroundThe use of the internet to look for information about vaccines has skyrocketed in the last years, especially with the COVID-19 pandemic. Digital vaccine literacy (DVL) refers to understanding, trust, appraisal, and application of vaccine-related information online. ObjectiveThis study aims to develop a tool measuring DVL and assess its psychometric properties. MethodsA 7-item online questionnaire was administered to 848 French adults. Different psychometric analyses were performed, including descriptive statistics, exploratory factor analysis, confirmatory factor analysis, and convergent and discriminant validity. ResultsWe developed the 7-item DVL scale composed of 3 factors (understanding and trust official information; understanding and trust information in social media; and appraisal of vaccine information online in terms of evaluation of the information and its application for decision making). The mean DVL score of the baseline sample of 848 participants was 19.5 (SD 2.8) with a range of 7-28. The median score was 20. Scores were significantly different by gender (P=.24), age (P=.03), studying or working in the field of health (P=.01), and receiving regular seasonal flu shots (P=.01). ConclusionsThe DVL tool showed good psychometric proprieties, resulting in a promising measure of DVL.

Abstract Previous studies have shown the negative impact of the COVID-19 epidemic on students’ mental health. It is, however, uncertain whether students are really at higher risk of mental health disturbances than non-students and if they are differentially impacted by lockdown periods over time. The objective of our study was to compare the frequency of depressive symptoms, anxiety, and suicidal thoughts in students and non-students enrolled in the same study in France and during the same key periods of the COVID-19 epidemic. Using a repeated cross-sectional design, we collected data from a sample of 3783 participants in the CONFINS study during three recruitment waves between March 2020 and January 2021. Multivariate logistic regression models, adjusted for potential confounding factors, showed that students were more likely to have high scores of depressive symptoms and anxiety more frequently than non-students. These differences were particularly strong during the first (depressive symptoms: adjusted odds ratio aOR 1.59, 95% CI 1.22–2.08; anxiety: aOR 1.63, 95% CI 1.22–2.18) and second lockdowns (depressive symptoms: aOR 1.80, 95% CI 1.04–3.12; anxiety: aOR 2.25, 95% CI 1.24–4.10). These findings suggest that the restrictive measures—lockdown and curfew—have an alarmingly stronger negative impact on students than on non-students and underline the frailty of students’ mental health and the need to pay greater attention to this population in this epidemic-related context.

Abstract Background Childhood maltreatment and peer victimization are major risk factors for depression and suicidal behavior. Furthermore, childhood maltreatment increases the risk of peer victimization. Our objective was to distinguish between the contributions of parental maltreatment and peer victimization to the development of mental health problems in young adulthood. Specifically, we tested whether peer victimization alone or in combination with parental maltreatment before 18 years old was associated with anxiety, depression, and suicidal thoughts and behaviors at age 21 years. Methods We analyzed data collected from questionnaires administered in the i-Share (Internet-based Students’ Health ResearchEnterprise) study in France from February 2013 to September 2019 (N = 2271 participants). We performed multinomial and binary logistic regression analyses to assess the single and combined contributions of childhood peer victimization and parental maltreatment to anxiety, depression, and suicidality in adulthood. Results Nearly one third of students (28.8%) reported at least one mental health problem; 29.8% reported peer victimization alone; 7.5% reported parental maltreatment alone; and 10.3% reported both parental maltreatment and victimization. In multivariate models, compared to participants that did not experience maltreatment or peer victimization, those that experienced peer victimization alone were more likely to report anxiety (adjusted odds ratio [aOR]: 1.90; 95% CI: 1.50–2.40), depression (aOR: 1.95; 95% CI: 1.46–2.60), or suicidal ideation, without (aOR: 1.62; 95% CI: 1.26–2.09) or with a suicide attempt (aOR: 2.70; 95% CI: 1.51–4.85). Similar associations were observed for participants that experienced maltreatment alone. Participants that experienced both maltreatment and peer victimization were at increased risk of depression (aOR: 2.63; 95% CI: 1.79–3.86) and suicidal ideation, with (aOR: 9.19; 95% CI: 4.98–16.92) and without a suicide attempt (aOR: 2.64; 95% CI: 1.86–3.76). Conclusions Separate and combined exposures to parental maltreatment and peer victimization in childhood or adolescence were associated with increased risks of anxiety, depression, and suicidal behaviors. Peer victimization appeared to play a specific role in mental health disorders that were not otherwise explained by polyvictimization. Currently, peer victimization is a frequent, but avoidable type of child abuse; therefore, these findings have implications for policies for preventing and dealing with peer victimization.

Abstract Suicidal thoughts and behaviours are prevalent among college students. Yet little is known about screening tools to identify students at higher risk. We aimed to develop a risk algorithm to identify the main predictors of suicidal thoughts and behaviours among college students within one-year of baseline assessment. We used data collected in 2013–2019 from the French i-Share cohort, a longitudinal population-based study including 5066 volunteer students. To predict suicidal thoughts and behaviours at follow-up, we used random forests models with 70 potential predictors measured at baseline, including sociodemographic and familial characteristics, mental health and substance use. Model performance was measured using the area under the receiver operating curve (AUC), sensitivity, and positive predictive value. At follow-up, 17.4% of girls and 16.8% of boys reported suicidal thoughts and behaviours. The models achieved good predictive performance: AUC, 0.8; sensitivity, 79% for girls, 81% for boys; and positive predictive value, 40% for girls and 36% for boys. Among the 70 potential predictors, four showed the highest predictive power: 12-month suicidal thoughts, trait anxiety, depression symptoms, and self-esteem. We identified a parsimonious set of mental health indicators that accurately predicted one-year suicidal thoughts and behaviours in a community sample of college students.

White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

AbstractBackgroundCannabis use in university students is associated with academic achievement failure and health issues. The objective of the study was to evaluate the association between attention deficit hyperactivity disorder (ADHD) symptoms and cannabis use after 1 year among students according to previous cannabis use.MethodsStudents in France were recruited from February 2013 to July 2020 in the i-Share cohort. 4,270 participants were included (2,135 who never used cannabis at inclusion and 2,135 who did). The Adult ADHD Self-Report Scale (ASRS) was used to assess ADHD symptoms at inclusion. Cannabis use frequency was evaluated 1 year after inclusion. Multinomial regressions were conducted to assess the association between inclusion ADHD symptoms and cannabis use after 1 year.ResultsIncrease in ASRS scores was linked with a greater probability to use cannabis after 1 year and to have a higher cannabis use frequency (once a year—once a month adjusted odds ratio [OR]: 1.24 (1.15–1.34), more than once a month adjusted OR: 1.43 (1.27–1.61)). Among participants who never used cannabis at inclusion, this association disappeared (once a year—once a month adjusted OR: 1.15 (0.95–1.39), more than once a month adjusted OR: 1.16 (0.67–2)) but remained in participants who ever used cannabis at inclusion (once a year—once a month adjusted OR: 1.17 (1.06–1.29), more than once a month adjusted OR: 1.35 (1.18–1.55)).ConclusionsHigh levels of ADHD symptoms in students could lead to continued cannabis use rather than new initiations.

Human brain white matter undergoes a protracted maturation that continues well into adulthood. Recent advances in diffusion-weighted imaging (DWI) methods allow detailed characterizations of the microstructural architecture of white matter, and they are increasingly utilized to study white matter changes during development and aging. However, relatively little is known about the late maturational changes in the microstructural architecture of white matter during post-adolescence. Here we report on regional changes in white matter volume and microstructure in young adults undergoing university-level education. As part of the MRi-Share multi-modal brain MRI database, multi-shell, high angular resolution DWI data were acquired in a unique sample of 1,713 university students aged 18–26. We assessed the age and sex dependence of diffusion metrics derived from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) in the white matter regions as defined in the John Hopkins University (JHU) white matter labels atlas. We demonstrate that while regional white matter volume is relatively stable over the age range of our sample, the white matter microstructural properties show clear age-related variations. Globally, it is characterized by a robust increase in neurite density index (NDI), and to a lesser extent, orientation dispersion index (ODI). These changes are accompanied by a decrease in diffusivity. In contrast, there is minimal age-related variation in fractional anisotropy. There are regional variations in these microstructural changes: some tracts, most notably cingulum bundles, show a strong age-related increase in NDI coupled with decreases in radial and mean diffusivity, while others, mainly cortico-spinal projection tracts, primarily show an ODI increase and axial diffusivity decrease. These age-related variations are not different between males and females, but males show higher NDI and ODI and lower diffusivity than females across many tracts. These findings emphasize the complexity of changes in white matter structure occurring in this critical period of late maturation in early adulthood.

Objectives To estimate the effect of student status on mental health condition during COVID-19 general lockdown in France.Design Cross-sectional analysis comparing students and non-students recruited in the same study.Setting Participants of the web-based CONFINS study implemented during the general lockdown in France in spring 2020.Participants 2260 participants (78% women) including 1335 students (59%).Primary and secondary outcome measures Through an online questionnaire, participants declared if they have experienced suicidal thoughts, coded their perceived stress on a 10-points scale and completed validated mental health scales (Patient Health Questionnaire-9 for depressive symptoms, Generalised Anxiety Disorder-7 for anxiety symptoms) during the last 7 days. The effect of college student status on each mental health condition was estimated using multivariate logistic regression analyses. Stratified models for students and non-students were performed to identify population-specific factors.Results Student status was associated with a higher frequency of depressive symptoms (adjusted OR (aOR)=1.58; 95% CI 1.17 to 2.14), anxiety symptoms (aOR=1.51; 95% CI 1.10 to 2.07), perceived stress (n=1919, aOR=1.70, 95% CI 1.26 to 2.29) and suicidal thoughts (n=1919, aOR=1.57, 95% CI 0.97 to 2.53). Lockdown conditions that could be potentially aggravating on mental health like isolation had a higher impact on students than on non-students.Conclusions College students were at higher risk of mental health disturbances during lockdown than non-students, even after taking into account several potential confounding factors. A close follow-up and monitoring of students’ mental health status is warranted during lockdown periods in this vulnerable population.

We implemented a deep learning (DL) algorithm for the 3-dimensional segmentation of perivascular spaces (PVSs) in deep white matter (DWM) and basal ganglia (BG). This algorithm is based on an autoencoder and a U-shaped network (U-net), and was trained and tested using T1-weighted magnetic resonance imaging (MRI) data from a large database of 1,832 healthy young adults. An important feature of this approach is the ability to learn from relatively sparse data, which gives the present algorithm a major advantage over other DL algorithms. Here, we trained the algorithm with 40 T1-weighted MRI datasets in which all “visible” PVSs were manually annotated by an experienced operator. After learning, performance was assessed using another set of 10 MRI scans from the same database in which PVSs were also traced by the same operator and were checked by consensus with another experienced operator. The Sorensen-Dice coefficients for PVS voxel detection in DWM (resp. BG) were 0.51 (resp. 0.66), and 0.64 (resp. 0.71) for PVS cluster detection (volume threshold of 0.5 within a range of 0 to 1). Dice values above 0.90 could be reached for detecting PVSs larger than 10 mm3 and 0.95 for PVSs larger than 15 mm3. We then applied the trained algorithm to the rest of the database (1,782 individuals). The individual PVS load provided by the algorithm showed a high agreement with a semi-quantitative visual rating done by an independent expert rater, both for DWM and for BG. Finally, we applied the trained algorithm to an age-matched sample from another MRI database acquired using a different scanner. We obtained a very similar distribution of PVS load, demonstrating the interoperability of this algorithm.

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

Background and Objectives: Young adults represent an increasingly large proportion of healthy volunteers in brain imaging research, but descriptions of incidental findings (IFs) in this age group are scarce. We aimed to assess the prevalence and severity of IFs on brain MRIs of healthy young research participants aged 18–35 years, and to describe the protocol implemented to handle them.Methods: The study population comprised 1,867 participants aged 22.1 ± 2.3 years (72% women) from MRi-Share, the cross-sectional brain MRI substudy of the i-Share student cohort. IFs were flagged during the MRI quality control. We estimated the proportion of participants with IFs [any, requiring medical referral, potentially serious (PSIFs) as defined in the UK biobank]: overall, by type and severity of the final diagnosis, as well as the number of IFs.Results: 78/1,867 participants had at least one IF [4.2%, 95% Confidence Interval (CI) 3.4–5.2%]. IFs requiring medical referral (n = 38) were observed in 36/1,867 participants (1.9%, 1.4–2.7%), and represented 47.5% of the 80 IFs initially flagged. Referred IFs were retrospectively classified as PSIFs in 25/1,867 participants (1.3%, 0.9–2.0%), accounting for 68.4% of anomalies referred (26/38). The most common final diagnosis was cysts or ventricular abnormalities in all participants (9/1,867; 0.5%, 0.2–0.9%) and in those with referred IFs (9/36; 25.0%, 13.6–41.3%), while it was multiple sclerosis or radiologically isolated syndrome in participants with PSIFs (5/19; 26.3%, 11.5–49.1%) who represented 0.1% (0.0–0.4%) and 0.2% (0.03–0.5%) of all participants, respectively. Final diagnoses were considered serious in 11/1,867 participants (0.6%, 0.3–1.1%). Among participants with referred IFs, 13.9% (5/36) required active intervention, while 50.0% (18/36) were put on clinical surveillance.Conclusions: In a large brain imaging study of young healthy adults participating in research we observed a non-negligible frequency of IFs. The etiological pattern differed from what has been described in older adults.

BackgroundThe ε4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association between APOE genotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of β-amyloid peptide (A, β-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD.Methods and findingsThis case-control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44-96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer's Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44-94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least one APOE ε4 allele. Compared with non-ε4 carriers, heterozygous ε4 carriers had a 4.6 (95% confidence interval 4.1-5.2; p < 0.001) and ε4/ε4 homozygotes a 25.4 (20.4-31.2; p < 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (p for interaction < 0.001). The PAF associated with carrying at least one ε4 allele was greatest in the 65-70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect of APOE ε2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD.ConclusionsIn this study, we found that AD diagnosis based on biomarkers was associated with APOE ε4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE ε4 at the population level.

OBJECTIVES Previous studies have reported controversial findings regarding the association of testosterone with mortality in older men. This heterogeneity might be partially explained by comorbidities and the presence of metabolic syndrome, as well as differential associations according to causes of death. METHODS We used data from a random subsample of the Three-City study, in which hormone levels were measured in 338 men ≥65 years without metabolic syndrome who were followed-up for 12 years. Vital status was determined for all participants from different sources. We used inverse-probability-weighted Cox regression to estimate the hazard ratios (HRs) of cause-specific mortality and 95% confidence intervals (CIs). RESULTS Over the follow-up period, 130 men died (30 from cardiovascular disease, 45 from cancer, 55 from other causes). The association of testosterone with mortality showed significant heterogeneity across causes of death (p=0.027 and p=0.022 for total and bioavailable testosterone, respectively). Higher testosterone levels were associated with increased cardiovascular mortality (HR for 1-standard deviation increase, 1.86; 95% CI, 1.28 to 2.71 and 1.50; 95% CI, 1.04 to 2.17 for total and bioavailable testosterone, respectively). By contrast, there were no significant associations of testosterone with mortality from cancer and other causes. CONCLUSIONS Our data suggest that the association of testosterone with mortality in men without metabolic syndrome might be differential according to the cause of death. These findings may partially explain the heterogeneity across studies on the relationship between testosterone levels and mortality.

Parameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, and RD), and more recently, peak width of skeletonized mean diffusivity (PSMD), have been proposed as potential markers of normal and pathological brain ageing. However, their relative evolution over the entire adult lifespan in healthy individuals remains partly unknown during early and late adulthood, and particularly for the PSMD index. Here, we gathered and analyzed cross-sectional diffusion tensor imaging (DTI) data from 10 population-based cohort studies in order to establish the time course of white matter water diffusion phenotypes from post-adolescence to late adulthood. DTI data were obtained from a total of 20,005 individuals aged 18.1 to 92.6 years and analyzed with the same pipeline for computing skeletonized DTI metrics from DTI maps. For each individual, MD, AD, RD, and FA mean values were computed over their FA volume skeleton, PSMD being calculated as the 90% peak width of the MD values distribution across the FA skeleton. Mean values of each DTI metric were found to strongly vary across cohorts, most likely due to major differences in DWI acquisition protocols as well as pre-processing and DTI model fitting. However, age effects on each DTI metric were found to be highly consistent across cohorts. RD, MD, and AD variations with age exhibited the same U-shape pattern, first slowly decreasing during post-adolescence until the age of 30, 40, and 50 years, respectively, then progressively increasing until late life. FA showed a reverse profile, initially increasing then continuously decreasing, slowly until the 70s, then sharply declining thereafter. By contrast, PSMD constantly increased, first slowly until the 60s, then more sharply. These results demonstrate that, in the general population, age affects PSMD in a manner different from that of other DTI metrics. The constant increase in PSMD throughout the entire adult life, including during post-adolescence, indicates that PSMD could be an early marker of the ageing process.

Background Research links blood pressure variability (BPV) with stroke; however, the association with cerebral small‐vessel disease (CSVD) remains unclear. As BPV and mean blood pressure are interrelated, it remains uncertain whether BPV adds additional information to understanding cerebrovascular morphological characteristics. Methods and Results A systematic review was performed from inception until March 3, 2019. Eligibility criteria included population, adults without stroke (

Abstract Background Suicidal ideation and suicidal risk assessment are major concerns for health professionals. The perception of a low level of parental support is a risk factor for suicidal tendencies among adolescents, but little is known about its long-term impact on the vulnerability to suicidal behavior in young adults. We investigated whether the perceived level of parental support during childhood and adolescence was associated with current suicidal ideation in young adults. Methods We retrieved data collected in the i-Share study from February 1st, 2013 through January 30, 2017. This cross-sectional study included 10,015 French students, aged 18–24 years that completed an on-line self-reported questionnaire about suicidal ideation in the last 12 months and their perceived parental support in childhood and adolescence. We performed multinomial logistic regressions and sensitivity analyses to assess associations between the degree of perceived parental support and the frequency suicidal thoughts, after adjusting for the main known risk factors of suicidal ideation. We employed multiple imputations to account for missing data. Results The study sample included 7539 female (75.7%) and 2436 male (24.3%) students (mean [SD] age 20.0 [1.8] years). About one in five students reported occasional suicidal thoughts (n = 1775, 17.7%) and 368 students (3.7%) reported frequent suicidal thoughts. The adjusted multinomial logistic regression revealed a significant negative association between perceived parental support and suicidal thoughts. A lack of perceived parental support in childhood and adolescence was associated with > 4-fold elevated risk of occasional (adjusted OR, 4.55; 95% CI: 2.97–6.99) and nearly 9-fold elevated risk of frequent (adjusted OR, 8.58; 95% CI: 4.62–15.96) suicidal thoughts, compared to individuals that perceived extremely strong parental support. This association was strongest among students with no personal history of depression or suicide attempts. Conclusions Students that perceived low levels of past parental support had a higher risk of suicidal ideation. Past perceived parental support appeared to be a potent marker of suicidal risk in young adults. This marker should be routinely collected in studies on suicidal risk in young adults, and it could be considered an additional screening tool.

Abstract Background Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease for which the genetic contribution is incompletely understood. Methods We conducted a joint analysis of 5,523,934 imputed SNPs in two newly-genotyped progressive supranuclear palsy cohorts, primarily derived from two clinical trials (Allon davunetide and NNIPPS riluzole trials in PSP) and a previously published genome-wide association study (GWAS), in total comprising 1646 cases and 10,662 controls of European ancestry. Results We identified 5 associated loci at a genome-wide significance threshold P

This study describes the production and evaluation of an online video explaining health insurance functioning to university students in France. The video was produced by a multidisciplinary team following a design thinking approach. A qualitative evaluation was performed using semi-structured interviews with 30 students. Results showed that, after watching the video, students had remarkably improved their knowledge and obtained clear information on health insurance functioning. This study underscores the importance of using innovative digital communication tools to efficaciously promote health insurance literacy.

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

Abstract Taller individuals walk faster but it is unknown whether this advantage persists at older ages. We examined the cross-sectional/longitudinal associations of height with gait speed (GS) in participants from the Dijon-Three-City cohort study (France) over 11 years. In 4011 participants (65–85 y), we measured usual/fast GS (6 m) up to five times. We examined whether the baseline height-GS association varied with age using linear regression, and whether height influenced GS change using linear mixed models. Taller participants 65 y at baseline walked faster than shorter ones (fast GS difference between top/bottom height quartiles, 0.100 m/s, P

Abstract Background Cognitive impairment is very common in late-life depression, principally affecting executive skills and information processing speed. The aim of the study was to examine the effect of antidepressant treatment on cognitive performances over a 10-year period. Methods The community-based cohort included 7381 participants aged 65 years and above. Five cognitive domains (verbal fluency, psychomotor speed, executive function, visuospatial skills and global cognition) were assessed up to five times over 10 years of follow-up. Treatment groups included participants under a specific antidepressant class at both baseline and the first follow-up and their follow-up cognitive data were considered until the last consecutive follow-up with a report of antidepressant use of the same class. Linear mixed models were used to compare baseline cognitive performance and cognitive decline over time according to antidepressant treatment. The models were adjusted for multiple confounders including residual depressive symptoms assessed by the Center for Epidemiologic Studies-Depression scale. Results At baseline, 4.0% of participants were taking antidepressants. Compared to non-users, tricyclic antidepressant users had lower baseline performances in verbal fluency, visual memory and psychomotor speed, and selective serotonin reuptake inhibitor users in verbal fluency and psychomotor speed. For the two other cognitive abilities, executive function and global cognition, no significant differences were found at baseline irrespective of the antidepressant class. Regarding changes over time, no significant differences were observed in comparison with non-users whatever the cognitive domain, except for a slight additional improvement over the follow-up in verbal fluency skills for tricyclic antidepressant users. Conclusions In this large elderly general population cohort, we found no evidence for an association between antidepressant use and post-treatment cognitive decline over 10 years of follow-up in various cognitive domains.

Chronic kidney disease (CKD) is often associated with poor hypertension control and treatment resistance, but whether CKD modifies the effect of hypertension control on outcomes is unknown. Methods: We studied 10-year mortality and cardiovascular events according to hypertension control status and CKD (glomerular filtration rate

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

ObjectivesThe aim of the study was to estimate the association between self-esteem and subsequent self-rated health during college years, taking into account a wide range of potential confounders.DesignProspective longitudinal study.SettingThe French i-Share cohort.ParticipantsThe sample consisted of 1011 college students.Primary and secondary outcome measuresThe association between self-esteem and later self-rated health was evaluated using multivariate modelling.Data regarding self-rated health, global self-esteem and demographic, educational, social, behavioural, environmental and financial characteristics were collected through an internet-based questionnaire.ResultsThe 1011 participants had a median age of 21.9 years and 79% (795/1011) were females. Self-rated health was assessed a median of 8 months after the self-esteem measurement. Twenty per cent of the students declared average to very poor health (203/1011). Students with higher levels of self-esteem were more likely to declare good or very good self-rated health (adjusted OR=1.40, 95% CI 1.15 to 1.72, p value=0.001). Other factors associated with good or very good self-rated health were low body mass index, a comfortable financial situation during childhood and three personality traits (low persistence and harm avoidance and high cooperativeness).ConclusionsThis study offers novel findings on the impact of self-esteem on self-rated health among college students. Interventions targeting self-esteem should be experimented during university years in order to improve health outcomes.

Background: Anxiety is common in patients with cognitive impairment and dementia. However, whether anxiety is a risk factor for dementia is still not known. We aimed to examine the association between trait anxiety at baseline and the 10-year risk of incident dementia to determine to which extent depressive symptoms influence this relationship in the general population.Methods: Data came from 5,234 community-dwelling participants from the Three-City prospective cohort study, aged 65 years at baseline and followed over 10 years. At baseline, anxiety trait was assessed using the Spielberger State-Trait Anxiety Inventory (STAI), and depressive symptoms using Center for Epidemiologic Studies-Depression Scale (CESD). Use of anxiolytic drugs was also considered. Diagnoses of dementia were made at baseline and every 2 years. To examine the relationship between anxiety exposures and risk of incident dementia, Cox proportional hazard regression models were performed.Results: Taking anxiolytic drugs or having high trait anxiety (STAI score ≥ 44) increased the risk of dementia assessed over 10 years of follow-up [Hazard Ratio (HR) = 1.39, 95%CI: 1.08–1.80, p = 0.01 and HR = 1.26, 95%CI: 1.01–1.57, p = 0.04, respectively], independently of a large panel of socio-demographic variables, health behaviors, cardio-metabolic disorders, and additional age-related disorders such as cardiovascular diseases, activity limitations, and cognitive deficit. However, the associations were substantially attenuated after further adjustment for depressive symptoms.Conclusion: Our findings suggest that depressive symptoms shape the association between anxiety trait and dementia. Further research is needed to replicate our findings and extrapolate our results to anxiety disorders.

To identify patterns summarizing the retinal vascular network in the elderly and to investigate the relationship of these vascular patterns with cardiovascular history.We conducted a population-based study, the Montrachet study (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases), in participants older than 75 years. The history of cardiovascular disease and a score-based estimation of their 10-year risk of cardiovascular mortality (Heart SCORE) were collected. Retinal vascular network analysis was performed by means of Singapore "I" Vessel Assessment (SIVA) software. Principal component analysis was used to condense the information contained in the high number of variables provided and to identify independent retinal vascular patterns.Overall, 1069 photographs (1069 participants) were reviewed with SIVA software. The mean age was 80.0 ± 3.8 years. We extracted three vascular patterns summarizing 41.3% of the vascular information. The most clinically relevant pattern, Sparse vascular network, accounted for 17.4% of the total variance. It corresponded to a lower density in the vascular network and higher variability in vessel width. Diabetic participants with hypoglycemic treatment had a sparser vascular network pattern than subjects without such treatment (odds ratio, [OR], 1.68; 95% CI, 1.04-2.72; P = 0.04). Participants with no history of cardiovascular disease who had a sparser vascular network were associated with a higher Heart SCORE (OR, 1.76; 95% CI, 1.08-2.25; P = 0.02).Three vascular patterns were identified. The Sparse vascular network pattern was associated with having a higher risk profile for cardiovascular mortality risk at 10 years.

BACKGROUND:Vascular risk factors have been proposed as important targets for the prevention of dementia. As lipid fractions represent easily modifiable targets, we examined the longitudinal relationship of baseline lipid fractions with 13-y incident dementia and its subtypes (Alzheimer disease [AD] and mixed or vascular dementia) in older community-dwelling persons. METHODS AND FINDINGS:Non-institutionalized persons aged 65+ y (n = 9,294) were recruited for the Three-City Study (3C Study), a population-based cohort study from the electoral rolls of the cities of Dijon, Bordeaux, and Montpellier, France, between March 1999 and March 2001. Follow-up examinations were performed every 2 y after the baseline assessment. The final study sample comprised 7,470 participants from the 3C Study (mean age ± standard deviation [SD] 73.8 ± 5.3 y, 61.0% women) who were prospectively followed up for up to 13 y. Fasting lipid fractions (triglycerides [TGs], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC]) were studied as continuous variables, and results are reported per SD increase of each lipid fraction. Incident dementia and its subtypes were studied as censored variables using Cox models with age as time scale. Analyses were adjusted for sex, study center, and educational level, as well as vascular risk factors and apolipoprotein E (APOE) ε4 genotype. We corrected for multiple testing, yielding a significance threshold of 0.0169. p-Values above the significance threshold but less than 0.05 were considered nominally significant. During a mean (± SD) follow-up period of 7.9 ± 3.6 y, 779 participants developed incident dementia (n = 532 AD and n = 154 mixed or vascular dementia). Higher LDL-C and TC concentrations at baseline were associated with an increased risk of AD (hazard ratio [HR] per SD increase = 1.13 [95% CI 1.04-1.22], p = 0.0045, and HR = 1.12 [1.03-1.22], p = 0.0072, respectively). These associations were largely unchanged after adjustment for vascular risk factors and were attenuated after adjustment for APOEε4 (HR per SD increase = 1.12 [1.03-1.23], p = 0.0110, and HR = 1.12 [1.02-1.23], p = 0.0171, respectively). Higher TG concentrations at baseline were associated with an increased risk of all dementia (HR per SD increase = 1.11 [1.03-1.19], p = 0.0044) and mixed or vascular dementia (HR = 1.21 [1.04-1.41], p = 0.0163). However, these associations disappeared after adjusting for vascular risk factors (HR = 1.07 [0.98-1.17], p = 0.1374, and HR = 1.17 [0.96-1.42], p = 0.1206, respectively). Main limitations of the study include interval censoring of incident dementia cases, potential selective survival bias, and the fact that variation in lipid concentrations during follow-up could not be accounted for in the analyses. CONCLUSIONS:In a large population-based sample of older community-dwelling persons with up to 13 y of follow-up, we observed that higher LDL-C and TC concentrations were associated with an increased risk of AD. This result was independent of vascular risk factors and was attenuated after adjustment for APOEε4 carrier status. TG and HDL-C concentrations were not associated with risk of incident dementia or its subtypes after accounting for vascular risk factors.

BACKGROUND:Cross-sectional studies show a strong association between chronic kidney disease and apparent treatment-resistant hypertension, but the longitudinal association of the rate of kidney function decline with the risk of resistant hypertension is unknown. METHODS:The population-based Three-City included 8,695 participants older than 65 years, 4265 of them treated for hypertension. We estimated the odds ratios (OR) of new-onset apparent treatment-resistant hypertension, defined as blood pressure ≥ 140/90 mmHg despite use of 3 antihypertensive drug classes or ≥ 4 classes regardless of blood pressure, associated with the mean estimated glomerular filtration rate (eGFR) level and its rate of decline over 4 years, compared with both controlled hypertension and uncontrolled nonresistant hypertension with ≤ 2 drugs. GFR was estimated with three different equations. RESULTS:Baseline prevalence of apparent treatment-resistant hypertension and of controlled and uncontrolled nonresistant hypertension, were 6.5%, 62.3% and 31.2%, respectively. During follow-up, 162 participants developed apparent treatment-resistant hypertension. Mean eGFR decline with the MDRD equation was 1.5±2.9 mL/min/1.73 m² per year: 27.7% of the participants had an eGFR ≥3 and 10.1% ≥ 5 mL/min/1.73 m² per year. After adjusting for age, sex, obesity, diabetes, and cardiovascular history, the ORs for new-onset apparent treatment-resistant hypertension associated with a mean eGFR level, per 15 mL/min/1.73 m² drop, were 1.23 [95% confidence interval 0.91-1.64] compared to controlled hypertension and 1.10 [0.83-1.45] compared to uncontrolled nonresistant hypertension; ORs associated with a decline rate ≥ 3 mL/min/1.73 m² per year were 1.89 [1.09-3.29] and 1.99 [1.19-3.35], respectively. Similar results were obtained when we estimated GFR with the CKDEPI and the BIS1 equations. ORs tended to be higher for an eGFR decline rate ≥ 5 mL/min/1.73 m² per year. CONCLUSION:The speed of kidney function decline is associated more strongly than kidney function itself with the risk of apparent treatment-resistant hypertension in the elderly.

BackgroundThe Global Burden of Diseases Study 2010 reported that hypertension is worldwide the leading risk factor for cardiovascular disease, causing 9.4 million deaths annually. We examined to what extent self-measurement of home blood pressure (HBP) refines risk stratification across increasing categories of conventional blood pressure (CBP).Methods and findingsThis meta-analysis included 5,008 individuals randomly recruited from five populations (56.6% women; mean age, 57.1 y). All were not treated with antihypertensive drugs. In multivariable analyses, hazard ratios (HRs) associated with 10-mm Hg increases in systolic HBP were computed across CBP categories, using the following systolic/diastolic CBP thresholds (in mm Hg): optimal, ConclusionsHBP substantially refines risk stratification at CBP levels assumed to carry no or only mildly increased risk, in particular in the presence of masked hypertension. Randomized trials could help determine the best use of CBP vs. HBP in guiding BP management. Our study identified a novel indication for HBP, which, in view of its low cost and the increased availability of electronic communication, might be globally applicable, even in remote areas or in low-resource settings.

To characterize the neuroanatomical changes in healthy older adults is important to differentiate pathological from normal brain structural aging. The present study investigated the annualized rate of GM atrophy in a large sample of older participants, focusing on the hippocampus, and searching for modulation by age and sex. In this 4-year longitudinal community cohort study, we used a VBM analysis to estimate the annualized rate of GM loss, at both the global and regional levels, in 1,172 healthy older adults (65-82 years) scanned at 1.5T. The global annualized rate of GM was -4.0 cm3/year (-0.83%/year). The highest rates of regional GM loss were found in the frontal and parietal cortices, middle occipital gyri, temporal cortex and hippocampus. The rate of GM atrophy was higher in women (-4.7 cm3/year, -0.91%/year) than men (-3.3 cm3/year, -0.65%/year). The global annualized rate of GM atrophy remained constant throughout the age range of the cohort, in both sexes. This pattern was replicated at the regional level, with the exception of the hippocampi, which showed a rate of GM atrophy that accelerated with age (2.8%/year per year of age) similarly for men and women. The present study reports a global and regional description of the annualized rate of grey matter loss and its evolution after the age of 65. Our results suggest greater anatomical vulnerability of women in late life and highlight a specific vulnerability of the hippocampus to the aging processes after 65 years of age.

BACKGROUND:Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. PRINCIPAL FINDINGS:In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci. SIGNIFICANCE:The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

OBJECTIVE: To examine 1) the associations between history of cardio-cerebrovascular diseases (CVD) and insomnia complaints and excessive daytime sleepiness (EDS), and 2) the relationships between sleep complaints and future CVD in persons over 65. METHODS: CVD was assessed at baseline and during two, four, and six-year follow-up in 5494 non-demented subjects. Self-reported insomnia complaints (poor sleep quality, difficulty in initiating sleep, difficulty in maintening sleep, and early morning awakening), EDS and sleep medication use were evaluated at baseline. Logistic regression models and Cox proportional hazard models, with delayed entry and age of participants as the time scale, were adjusted for socio-demographic, lifestyle and clinical variables. RESULTS: At baseline, 748 participants had a past-history of CVD. A past-history of CVD was associated with EDS (OR = 1.28 95%CI = [1.05-1.57]) and the number of insomnia complaints (OR = 1.26 95%CI = [1.03-1.55] for 1-2 insomnia complaints; OR = 1.32 95%CI = [1.03-1.71] for ≥3 complaints). In longitudinal analyses, neither the four components of insomnia nor the number of insomnia complaints were significantly associated with first or recurrent CVD events (n = 391 events). EDS was independently associated with future CVD events even after adjusting for prescribed sleep medication and past-history of CVD (HR = 1.35 95%CI = [1.06-1.71]). CONCLUSION: Our results suggest that the relationships between sleep complaints and CVD could be complex. Insomnia complaints are more likely a consequence of CVD, whereas EDS appears to be a determinant of CVD independently of past-history of CVD. EDS screening may thus constitute a means of detecting persons at high risk of CVD.

BackgroundAß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively).Methodology/principal findingsPlasma Aß(1-40) and Aß(1-42) levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) and the Australian, longitudinal AIBL study (n = 576). In the combined sample, the Aß(1-42)/ Aß(1-40) ratio was significantly and inversely associated with SBP (p = 0.03) and a similar trend was observed for DBP (p = 0.06). Using the median age (69) as a cut-off, the Aß(1-42)/Aß(1-40) ratio was strongly associated with both SBP and DBP in elderly individuals (p = 0.002 and p = 0.03, respectively). Consistently, a high Aß(1-42)/ Aß(1-40) ratio was associated with a lower risk of hypertension in both the combined whole sample (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.56-0.90) and (to an even greater extent) in the elderly subjects (OR, 0.53; 95% CI, 0.37-0.75). Lastly, all these associations appeared to be primarily driven by the level of plasma Aß(1-40).ConclusionThe plasma Aß(1-42)/Aß(1-40) ratio is inversely associated with SBP, DBP and the risk of hypertension in elderly subjects, suggesting that Aß peptides affect blood pressure in vivo. These results may be particularly relevant in Alzheimer's disease, in which a high Aß(1-42)/Aß(1-40) plasma ratio is reportedly associated with a decreased risk of incident disease.