Modulate the impact of the drowsiness on the resting state functional connectivity.

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.

Factors related to increased alcohol misuse by students compared to non-students during the first Covid-19 lockdown in France: the Confins study.

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.

Brain artery diameters and risk of dementia and stroke.

INTRODUCTION: We tested the association of brain artery diameters with dementia and stroke risk in three distinct population-based studies using conventional T2-weighted brain magnetic resonance imaging (MRI) images. METHODS: We included 8420 adults > 40 years old from three longitudinal population-based studies with brain MRI scans. We estimated and meta-analyzed the hazard ratios (HRs) of the brain and carotids and basilar diameters associated with dementia and stroke. RESULT: Overall and carotid artery diameters > 95th percentile increased the risk for dementia by 1.74 (95% confidence interval [CI], 1.13-2.68) and 1.48 (95% CI, 1.12-1.96) fold, respectively. For stroke, meta-analyses yielded HRs of 1.59 (95% CI, 1.04-2.42) for overall arteries and 2.11 (95% CI, 1.45-3.08) for basilar artery diameters > 95th percentile. DISCUSSION: Individuals with dilated brain arteries are at higher risk for dementia and stroke, across distinct populations. Our findings underline the potential value of T2-weighted brain MRI-based brain diameter assessment in estimating the risk of dementia and stroke.

Prevalence, lived experiences and user profiles in e-cigarette use: A mixed methods study among French college students.

BACKGROUND: Little 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. METHODS: We 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. RESULTS: The 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. CONCLUSION: Despite 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.

Adverse Childhood Experiences and Illegal Drug Use Among College Students: Findings from a French Sample.

BACKGROUND: While studies have demonstrated the negative impact of adverse childhood experiences (ACEs) on lifelong health, less is known about the relationship between ACEs and illegal drug use. Thus, the objective of the study was to examine the relationship between ACEs and illegal drug use among college students. METHODS: French college students between 18 and 30 years enrolled in a university cohort study were eligible for inclusion. Multivariate logistic regression models were conducted for each drug. RESULTS: Among the sample (n = 1,157), 30.6% had no ACE exposure, 29.6%, 19.2%, and 20.7% had 1, 2 and ≥ 3 ACEs, respectively. Students with ACEs had a higher likelihood of using illegal drugs (p = 0.0067). After controlling for potential confounders, having ≥ 3 ACEs increased the risk of lifetime use of multiple drugs (aOR:10.9; 95% CI: 4.6-26.0), stimulants (aOR: 3.6; 95% CI:1.7-7.7), hallucinogens (aOR: 2.0; 95% CI: 1.1-3.5), cannabis (aOR: 4.7; 95% CI: 2.7-8.0), and risky illegal drugs (e.g., higher lifetime frequency drug use) (aOR: 2.9; 95% CI: 1.5-5.8). Estimates for illegal drug use were highest with parental substance use (aOR: 2.6; 95% CI; 1.5-4.4), sexual abuse (aOR: 2.3; 95% CI; 1.4-3.8), and divorce (aOR: 1.9; 95% CI: 1.3-2.7). CONCLUSIONS: ACEs increase the risk for lifetime illegal drug use and risky drug use in a dose-respondent fashion. These findings suggest that university students with higher levels of ACEs may benefit from additional support and services from clinical practitioners and university administrators.

Early detection of white matter hyperintensities using SHIVA-WMH detector.

White matter hyperintensities (WMHs) are well-established markers of cerebral small vessel disease, and are associated with an increased risk of stroke, dementia, and mortality. Although their prevalence increases with age, small and punctate WMHs have been reported with surprisingly high frequency even in young, neurologically asymptomatic adults. However, most automated methods to segment WMH published to date are not optimized for detecting small and sparse WMH. Here we present the SHIVA-WMH tool, a deep-learning (DL)-based automatic WMH segmentation tool that has been trained with manual segmentations of WMH in a wide range of WMH severity. We show that it is able to detect WMH with high efficiency in subjects with only small punctate WMH as well as in subjects with large WMHs (i.e., with confluency) in evaluation datasets from three distinct databases: magnetic resonance imaging-Share consisting of young university students, MICCAI 2017 WMH challenge dataset consisting of older patients from memory clinics, and UK Biobank with community-dwelling middle-aged and older adults. Across these three cohorts with a wide-ranging WMH load, our tool achieved voxel-level and individual lesion cluster-level Dice scores of 0.66 and 0.71, respectively, which were higher than for three reference tools tested: the lesion prediction algorithm implemented in the lesion segmentation toolbox (LPA: Schmidt), PGS tool, a DL-based algorithm and the current winner of the MICCAI 2017 WMH challenge (Park et al.), and HyperMapper tool (Mojiri Forooshani et al.), another DL-based method with high reported performance in subjects with mild WMH burden. Our tool is publicly and openly available to the research community to facilitate investigations of WMH across a wide range of severity in other cohorts, and to contribute to our understanding of the emergence and progression of WMH.

Addressing unmeasured confounders in cohort studies: Instrumental variable method for a time-fixed exposure on an outcome trajectory.

Instrumental variable methods, which handle unmeasured confounding by targeting the part of the exposure explained by an exogenous variable not subject to confounding, have gained much interest in observational studies. We consider the very frequent setting of estimating the unconfounded effect of an exposure measured at baseline on the subsequent trajectory of an outcome repeatedly measured over time. We didactically explain how to apply the instrumental variable method in such setting by adapting the two-stage classical methodology with (1) the prediction of the exposure according to the instrumental variable, (2) its inclusion into a mixed model to quantify the exposure association with the subsequent outcome trajectory, and (3) the computation of the estimated total variance. A simulation study illustrates the consequences of unmeasured confounding in classical analyses and the usefulness of the instrumental variable approach. The methodology is then applied to 6224 participants of the 3C cohort to estimate the association of type-2 diabetes with subsequent cognitive trajectory, using 42 genetic polymorphisms as instrumental variables. This contribution shows how to handle endogeneity when interested in repeated outcomes, along with a R implementation. However, it should still be used with caution as it relies on instrumental variable assumptions hardly testable in practice.

Adverse Childhood Experiences and ADHD Symptoms Among French College Students.

To examine the relationship between adverse childhood experiences (ACEs) and Attention-deficit Hyperactivity Disorder (ADHD) among college students. We investigated the association between ACEs and ADHD symptoms among French college students enrolled in the i-Share cohort using multivariate logistic regression models. The sample comprised of 1062 participants with a mean age of 20.3 (SD = 2.3) of which 30.6% had no ACEs exposure, 29.6% had 1 ACE, 19.2% had 2 ACEs, and 20.6% had ≥ 3 ACEs. After controlling for potential confounders, every increase in ACE exposure heightened the risk of ADHD symptoms with the respective adjusted Odds Ratios and 95% confidence intervals: 1 ACE: 2.1 (0.7-6.3) / 2 ACEs: 4.5 (2.6-12.8)/ ≥ 3 ACEs: 5.2 (1.8-14.8). Estimates for ADHD symptoms were higher with sexual abuse, emotional and physical neglect, and bullying. Findings suggest that ACEs heighten the risk for developing ADHD symptoms among college students and bear important implications for prevention and clinical practice.

Identification of circulating proteins associated with general cognitive function among middle-aged and older adults.

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 < 4.9E-5, n up to 7289). Of these, 45 were replicated using SomaScan data, and three were replicated using Olink data at Bonferroni-corrected significance. Enrichment analysis linked the proteins associated with general cognitive function to cell signaling pathways and synapse architecture. Mendelian randomization analysis implicated higher levels of NECTIN2, a protein mediating viral entry into neuronal cells, with higher Alzheimer's disease (AD) risk (p = 2.5E-26). Levels of 14 other protein measures were implicated as consequences of AD susceptibility (p < 2.0E-4). Proteins implicated as causes or consequences of AD susceptibility may provide new insight into the potential relationship between immunity and AD susceptibility as well as potential therapeutic targets.

Complexities of cerebral small vessel disease, blood pressure, and dementia relationship: new insights from genetics.

Importance: There is increasing recognition that vascular disease, which can be treated, is a key contributor to dementia risk. However, the contribution of specific markers of vascular disease is unclear and, as a consequence, optimal prevention strategies remain unclear. Objective: To disentangle the causal relation of several key vascular traits to dementia risk: (i) white matter hyperintensity (WMH) burden, a highly prevalent imaging marker of covert cerebral small vessel disease (cSVD); (ii) clinical stroke; and (iii) blood pressure (BP), the leading risk factor for cSVD and stroke, for which efficient therapies exist. To account for potential epidemiological biases inherent to late-onset conditions like dementia. Design Setting and Participants: This study first explored the association of genetically determined WMH, BP levels and stroke risk with AD using summary-level data from large genome-wide association studies (GWASs) in a two-sample Mendelian randomization (MR) framework. Second, leveraging individual-level data from large longitudinal population-based cohorts and biobanks with prospective dementia surveillance, the association of weighted genetic risk scores (wGRSs) for WMH, BP, and stroke with incident all-cause-dementia was explored using Cox-proportional hazard and multi-state models. The data analysis was performed from July 26, 2020, through July 24, 2022. Exposures: Genetically determined levels of WMH volume and BP (systolic, diastolic and pulse blood pressures) and genetic liability to stroke. Main outcomes and measures: The summary-level MR analyses focused on the outcomes from GWAS of clinically diagnosed AD (n-cases=21,982) and GWAS additionally including self-reported parental history of dementia as a proxy for AD diagnosis (ADmeta, n-cases=53,042). For the longitudinal analyses, individual-level data of 157,698 participants with 10,699 incident all-cause-dementia were studied, exploring AD, vascular or mixed dementia in secondary analyses. Results: In the two-sample MR analyses, WMH showed strong evidence for a causal association with increased risk of ADmeta (OR, 1.16; 95%CI:1.05-1.28; P=.003) and AD (OR, 1.28; 95%CI:1.07-1.53; P=.008), after accounting for genetically determined pulse pressure for the latter. Genetically predicted BP traits showed evidence for a protective association with both clinically defined AD and ADmeta, with evidence for confounding by shared genetic instruments. In longitudinal analyses the wGRSs for WMH, but not BP or stroke, showed suggestive association with incident all-cause-dementia (HR, 1.02; 95%CI:1.00-1.04; P=.06). BP and stroke wGRSs were strongly associated with mortality but there was no evidence for selective survival bias during follow-up. In secondary analyses, polygenic scores with more liberal instrument definition showed association of both WMH and stroke with all-cause-dementia, AD, and vascular or mixed dementia; associations of stroke, but not WMH, with dementia outcomes were markedly attenuated after adjusting for interim stroke. Conclusion: These findings provide converging evidence that WMH is a leading vascular contributor to dementia risk, which may better capture the brain damage caused by BP (and other etiologies) than BP itself and should be targeted in priority for dementia prevention in the population.

The role of cardiovascular health and vascular events in the relationship between excessive daytime sleepiness and dementia risk.

Many studies suggest a relationship between excessive daytime sleepiness (EDS) and dementia incidence, but the underlying mechanisms remain uncertain. The study aimed to investigate the role of cardiovascular burden in the relationship between EDS and dementia incidence over a 12-year follow-up in community-dwelling older adults. We performed analyses on 6171 subjects (aged ≥65 years) free of dementia and vascular disease at baseline. Participants self-reported EDS at baseline and an expert committee validated both prevalent and incident dementia. We defined cardiovascular burden by a low Cardiovascular Health score, constructed using the American Heart Association metrics, and incident vascular events. To explore the potential role of the cardiovascular burden in the relationship between EDS and dementia, we conducted mediation analyses with inverse odds ratio-weighted estimation, using multivariable-adjusted proportional hazard Cox and logistic regression models. Subjects with EDS had a higher risk of all-cause dementia (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.13-1.69) and dementia with vascular component (DVC) (HR 2.14, 95% CI 1.30-3.51), but not Alzheimer's disease (HR 1.18, 95% CI 0.93-1.51). Cardiovascular burden explained 5% (95% CI 4.1-5.2) and 11% (95% CI 9.7-11.3) of the relationship between EDS and all-cause dementia and DVC, respectively. These findings confirm that EDS may be implicated in the development of dementia and indicate a weaker than expected role of cardiovascular burden in the relationship between EDS and DVC.

Attention deficit hyperactivity disorder symptoms and lifetime use of psychoactive substances among French university students: A cross-sectional study.

In a cross sectional study of 13,837 university students, we aimed to explore the association between attention deficit hyperactivity disorder (ADHD) symptoms and lifetime psychoactive substance use (LPSU) on a wide range of illicit substances. Logistic and Hurdel multivariable regressions were used. ADHD symptoms were significantly associated with the lifetime use of ketamine, magic mushrooms, poppers, and nine other psychoactive substances. There was an association between ADHD symptoms and both LPSU and truncated count of lifetime psychoactive substance use. High levels of ADHD symptoms are associated with the use of a large variety and multiple LPSU.

Association of retinal nerve layers thickness and brain imaging in healthy young subjects from the i-Share-Bordeaux study.

Given the anatomical and functional similarities between the retina and the brain, the retina could be a "window" for viewing brain structures. We investigated the association between retinal nerve fiber layers (peripapillary retinal nerve fiber layer, ppRNFL; macular ganglion cell-inner plexiform layer, GC-IPL; and macular ganglion cell complex, GCC), and brain magnetic resonance imaging (MRI) parameters in young health adults. We included 857 students (mean age: 23.3 years, 71.3% women) from the i-Share study. We used multivariate linear models to study the cross-sectional association of each retinal nerve layer thickness assessed by spectral-domain optical coherence tomography (SD-OCT) with structural (volumes and cortical thickness), and microstructural brain markers, assessed on MRI globally and regionally. Microstructural MRI parameters included diffusion tensor imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI). On global brain analysis, thicker ppRNFL, GC-IPL and GCC were all significantly associated with patterns of diffusion metrics consistent with higher WM microstructural integrity. In regional analyses, after multiple testing corrections, our results suggested significant associations of some retinal nerve layers with brain regional gray matter occipital volumes and with diffusion MRI parameters in a region involved in the visual pathway and in regions containing associative tracts. No associations were found with global volumes or with global or regional cortical thicknesses. Results of this study suggest that some retinal nerve layers may reflect brain structures. Further studies are needed to confirm these results in young subjects.

Impact of interventions scenarios targeting three main vascular risk factors on the future burden of dementia in France.

The epidemiological and societal burden of dementia is expected to increase in the coming decades due to the world population aging. In this context, the evaluation of the potential impact of intervention scenarios aiming at reducing the prevalence of dementia risk factors is an active area of research. However, such studies must account for the associated changes in mortality and the dependence between the risk factors. Using micro-simulations, this study aims to estimate the changes in dementia burden in France in 2040 according to intervention scenarios targeting the prevention or treatment of hypertension, diabetes and physical inactivity. Accounting for their communality and their effects on mortality, the results show that the disappearance of hypertension, diabetes and physical inactivity in France in 2020 could decrease dementia prevalence by 33% among men and 26% among women in 2040 and increase the life expectancy without dementia at age 65 by 3.4 years (men) and 2.6 years (women). Among the three factors, the prevention of hypertension would be the most efficient. These projections rely on current estimates of the risk of dementia and death associated with risk factors. Thanks to the R package developed they could be refined for different countries or different interventions and updated with new estimates.

Study of the association between cannabis use and sleep disturbances in a large sample of University students.

Sleep complaints and cannabis use are common among University students and are related to detrimental effects on health. The aim of this study was to explore their association. This cross-sectional study based on the i-Share e-cohort included French students between 18 and 30 years old (n = 14,787). Frequency of cannabis use was categorized into daily, weekly, monthly, and never/rarely use. Sleep complaints were defined using four items (i.e., insomnia, sleepiness, poor sleep quality, and sleep deprivation). In the whole sample (mean age: 20.4 years, 75.5% of females), 22.7% had insomnia, 18.3% had sleepiness, 22.4% had poor sleep quality, 52.5% had sleep deprivation, and 5.8% used cannabis weekly or daily. After adjustment, the likelihood of insomnia was significantly higher by 45% in cannabis users compared to non-users. The estimates steadily increased with frequency of use, reaching a 2.0-fold higher likelihood of insomnia in daily users compared to never/rarely users. Results were similar for the other sleep complaints. These findings provide support for an association between cannabis use and sleep complaints, particularly insomnia, among University students. Though direction and causality cannot be established in this setting, these results suggest warning students and health professionals about the association between cannabis use and sleep complaints.

How Traumatic Brain Injury History Relates to Brain Health MRI Markers and Dementia Risk: Findings from the 3C Dijon Cohort.

BACKGROUND: The long-term effects of traumatic brain injury (TBI) with loss of consciousness (LOC) on magnetic resonance imaging (MRI) markers of brain health and on dementia risk are still debated. OBJECTIVE: To investigate the associations of history of TBI with LOC with incident dementia and neuroimaging markers of brain structure and small vessel disease lesions. METHODS: The analytical sample consisted in 4,144 participants aged 65 and older who were dementia-free at baseline from the Three City -Dijon study. History of TBI with LOC was self-reported at baseline. Clinical Dementia was assessed every two to three years, up to 12 years of follow-up. A subsample of 1,675 participants <80 years old underwent a brain MRI at baseline. We investigated the associations between history of TBI with LOC and 1) incident all cause and Alzheimer's disease (AD) dementia using illness-death models, and 2) neuroimaging markers at baseline. RESULTS: At baseline, 8.3% of the participants reported a history of TBI with LOC. In fully-adjusted models, participants with a history of TBI with LOC had no statistically significant differences in dementia risk (HR = 0.90, 95% CI = 0.60-1.36) or AD risk (HR = 1.03, 95% CI = 0.69-1.52), compared to participants without TBI history. History of TBI with LOC was associated with lower white matter volume (ß= -4.58, p = 0.048), but not with other brain volumes, white matter hyperintensities volume, nor covert brain infarct. CONCLUSION: This study did not find evidence of an association between history of TBI with LOC and dementia or AD dementia risks over 12-year follow-up, brain atrophy, or markers of small vessel disease.