Gaël Chételat

Unité Inserm U1077

Background and Objectives Self-reflection (the active evaluation of ones thoughts, feelings and behaviours) can confer protection against adverse health outcomes. Its impact on markers sensitive to Alzheimer’s disease (AD), however, is unknown. The primary objective of this cross-sectional study was to examine the association between self-reflectio...

The European Prevention of Alzheimer Dementia (EPAD) is a multi-center study that aims to characterize the preclinical and prodromal stages of Alzheimer's Disease. The EPAD imaging dataset includes core (3D T1w, 3D FLAIR) and advanced (ASL, diffusion MRI, and resting-state fMRI) MRI sequences. Here, we give an overview of the semi-automatic multimo...

Brain-age can be inferred from structural neuroimaging and compared to chronological age (brain-age delta) as a marker of biological brain aging. Accelerated aging has been found in neurodegenerative disorders like Alzheimer’s disease (AD), but its validation against markers of neurodegeneration and AD is lacking. Here, imaging-derived measures fro...

Tissue-type plasminogen activator (tPA) is a protease known for its fibrinolytic action but is also involved in physiological and pathophysiological aging processes; including amyloid elimination and synaptic plasticity. The aim of the study was to investigate the role of tPA in cognitive and brain aging. Therefore, we assessed the links between tP...

Background Depressive and anxiety symptoms are frequent in Alzheimer’s disease and associated with increased risk of developing Alzheimer’s disease in older adults. We sought to examine their relationships to Alzheimer’s disease biomarkers across the preclinical and clinical stages of the disease. Method Fifty-six healthy controls, 35 patients wit...

Vascular risk factors such as hyperglycemia and platelet hyperactivation play a significant role in type 2 diabetes (T2D), a risk factor for AD. We investigated the relationships between glycemia levels, platelet indices (platelet count; mean platelet volume (MPV)) and AD neuroimaging markers in 105 cognitively unimpaired adults, including 21 amylo...

Background: This study assesses the relationships between dynamic functional network connectivity (DFNC) and dementia risk. Methods: DFNC of the default mode (DMN), salience (SN), and executive control networks was assessed in 127 cognitively unimpaired older adults. Stepwise regressions were performed with dementia risk and protective factors a...

Objective 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 Participants from the Age-...

Background: Poor vascular health may impede brain functioning in older adults, thus possibly increasing the risk of cognitive decline and Alzheimer's disease (AD). The emerging link between vascular risk factors (VRF) and longitudinal decline in resting-state functional connectivity (RSFC) within functional brain networks needs replication and fur...

Introduction: Physical inactivity and female sex are independently associated with increased Alzheimer's disease (AD) lifetime risk. This study investigates the possible interactions between sex and physical activity on neuroimaging biomarkers. Methods: In 134 cognitively unimpaired older adults (≥65 years, 82 women) from the Age-Well randomized...

Objectif De récentes études ont mis en évidence chez le rongeur et de jeunes adultes un regroupement périodique des fuseaux de sommeil en trains, responsables d’une fluctuation de la puissance spectrale sigma avec une périodicité de ∼50s durant le sommeil NREM. Nous étudions ici ces aspects dynamiques des fuseaux chez le sujet âgé et leur lien avec...

Objectives Deepening our understanding of the mechanisms by which meditation practices impact well-being and human flourishing is essential for advancing the science of meditation. A recent phenomenologically grounded classification system distinguishes attentional, constructive, and deconstructive forms of meditation based on the psychological mec...

Importance: One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design. Objective:...

Medial temporal lobe (MTL) sub-structures are differentially affected in early Alzheimer’s disease (AD), with a specific involvement of the entorhinal cortex (ERC), the perirhinal cortex (PRC) and CA1. However, the impact of amyloid (Aβ) pathology and APOE ε4 on MTL subregional atrophy remains relatively unknown. Our aim was to uncover these effect...

Introduction: The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited. Methods: In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns,...

Informant‐reported subjective cognitive decline (I‐SCD) have been associated with objective cognitive decline and biomarkers of Alzheimer's disease (AD) in previous studies. However, we lack a comprehensive overview of these associations across the entire clinical continuum of the Alzheimer's syndrome allowing to stress whether there is a clinical...

Subclinical depressive symptoms are prevalent in older adults. They are associated with increased risk for both clinical depression and Alzheimer’s disease (AD), and may at least partly reflect early AD manifestations. However, the brain mechanisms underlying the relationship between depressive symptoms and AD remain to be elucidated. The aim of th...

Sleep‐disordered breathing (SDB) has been associated to greater amyloid deposition and dementia risk. However, the pattern of SDB‐associated structural brain changes is unclear, especially within the medial temporal lobe (MTL). We investigated the associations between SDB severity and the volume of MTL subregions, and hypothesized that SDB would be...

Medial temporal lobe (MTL) subregions, more specifically the CA1 subfield of the hippocampus and the entorhinal cortex (ERC), are particularly affected in Alzheimer’s disease (AD). However, the specific impact of amyloid (Aβ) pathology and APOE ε4 on MTL subregional atrophy remains relatively unknown. Our aim was to uncover these effects to further...

Medial temporal lobe (MTL) subregions are sensitive to Alzheimer’s disease (AD) but also to normal ageing. To enhance the clinical utility of this biomarker, we need to improve our understanding of the differential effects of age versus AD by i) encompassing the full clinical range from cognitively unimpaired (CU) to dementia, ii) including all MTL...

Subjective cognitive decline (SCD) denotes self‐reported cognitive concerns in the absence of objective cognitive impairment. Individuals with SCD convert to dementia at twice the annual rate of healthy controls, with relatively poorer cognition in SCD conferring additional risk. Non‐pharmacological interventions are currently undergoing intensive...

There is an increasing research focus on type 2 diabetes (T2D) as a risk factor for Alzheimer’s disease (AD) (Lee, 2018). T2D is a disease characterized notably by hyperglycemia and platelet hyper‐reactivity (Schneider, 2009). However, relatively little is known about subclinical but high levels of glycemia and platelet reactivity in the context of...

Sleep, especially slow wave sleep (SWS), favors efficient cognitive functioning. This effect may be impaired in aging, but might be modulated by cognitive reserve. Indeed, a study reported that highly educated older adults were able to better tolerate the negative effects of subjective sleep disturbances on verbal fluency scores. Growing evidence a...

The COVID‐19 pandemic and the associated distancing measures dramatically affect psychoaffective health, and this is accentuated in older adults who are more vulnerable to the situation. In this study, we are interested in the predictors of emotional resilience in healthy older adults, and also on how the repetition of confinement periods could inf...

Self‐reflection is conceptualised as an introspective process that involves active evaluation of one’s thoughts, feelings and behaviours. Engagement in self‐reflection is thought to yield more adaptive stress responses, that in turn result in better short‐term (e.g., reduced inflammatory responses to stressors) and long‐term (e.g., recovery from ma...

Neuroimaging biomarkers in large‐scale multimodal studies have proven effective for early diagnosis. Image‐derived phenotypes (IDPs) are summary features derived from modalities such as magnetic resonance imaging (MRI). We provide an overview of the IDPs computed from the European Prevention of Alzheimer Dementia (EPAD) cohort study, a multi‐center...

Physical activity (PA) has been associated with decreased risk of dementia, but the mechanisms underlying this association remain to be determined. One hypothesis is that PA might reduce cardiovascular risk factors (CVRFs), which in turn would benefit brain health. Our objective was to assess the role of CVRFs in the association between PA and neur...

White matter hyperintensities (WMH) are very frequent in ageing and related to worse cognition. Recent studies suggest that WMH in the corpus callosum (CC) are particularly relevant in neurocognitive disorders, as they are strongly associated with lower cognitive performance, as well as amyloid and neurodegeneration biomarkers. This study examined...

Structural MRI measurements can contribute to the prediction of amyloid pathology in cognitively unimpaired (CU) individuals. In this work, we aimed at studying the predictive capacity, robustness, and generalizability of ML techniques to predict amyloid‐β pathology in CU individuals, as well as identifying key brain regions contributing to this pr...

Gray matter network (GMN) disruptions correlate with amyloid burden in the earliest stages of Alzheimer’s Disease (AD) pathology in cognitively unimpaired individuals. However, it remains unknown if and how hyperphosphorylated tau (p‐tau) influences GMNs. Here, we investigated the relation between GMNs and cerebrospinal fluid (CSF) p‐tau181 levels...

As the population ages, understanding how to maintain older adults' cognitive abilities is essential. Bilingualism has been linked to higher cognitive reserve, better performance in executive control, changes in brain structure and function relative to monolinguals, and delay in dementia onset. Learning a second language thus seems a promising aven...

Background: The Lifetime of Experiences Questionnaire (LEQ) assesses complex mental activity across the life-course and has been associated with brain and cognitive health. The different education systems and occupation classifications across countries represent a challenge for international comparisons. The objectives of this study were four-fold:...

We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disea...

Although prevention of dementia and late-life cognitive decline is a major public health priority, there are currently no generally established prevention strategies or operational models for implementing such strategies into practice. This article is a narrative review of available evidence from multidomain dementia prevention trials targeting sev...

Dementia has a devastating impact on the quality of life of patients and families and comes with a huge cost to society. Dementia prevention is considered a public health priority by the World Health Organization. Delaying the onset of dementia by treating associated risk factors will bring huge individual and societal benefit. Empirical evidence s...

Cognitive complaints in the absence of objective cognitive impairment, observed in patients with subjective cognitive decline (SCD), are common in old age. The first step to postpone cognitive decline is to use techniques known to improve cognition, i.e., cognitive enhancement techniques. We aimed to provide clinical recommendations to improve cogn...

Background: Improving mental health in older adults is a priority in our aging societies. Anxiety and depressive symptoms are associated with impaired well-being, higher risk of developing psychoaffective disorders and are risk factors for Alzheimer's disease (AD). To further understand their relevance and the mechanisms underlying their link with...

The European Prevention of Alzheimer Dementia (EPAD) is a multi-center study that aims to characterize the preclinical and prodromal stages of Alzheimer’s Disease. The EPAD imaging dataset includes core (3D T1w, 3D FLAIR) and advanced (ASL, diffusion MRI, and resting-state fMRI) MRI sequences. Here, we give an overview of the semi-automatic multimo...

Medial temporal lobe (MTL) atrophy is a key feature of Alzheimer's disease (AD), however, it also occurs in typical aging. To enhance the clinical utility of this biomarker, we need to better understand the differential effects of age and AD by encompassing the full AD-continuum from cognitively unimpaired (CU) to dementia, including all MTL subreg...

Alzheimer's disease (AD) represents a major health and societal issue; there is no treatment to date and the pathophysiological mechanisms underlying this disease are not well understood. Yet, there is hope that AD risk factors and thus the number of AD cases can be significantly reduced by prevention measures based on lifestyle modifications as ta...

Subjective memory decline is associated with neurodegeneration and increased risk of cognitive decline in participants with no or subjective cognitive impairment, while in patients with mild cognitive impairment or Alzheimer’s-type dementia findings are inconsistent. Our aim was to provide a comprehensive overview of subjective memory decline chang...

Studies supporting a strong association between tau deposition and neuronal loss, neurodegeneration, and cognitive decline have heightened the allure of tau and tau‐related mechanisms as therapeutic targets. In February 2020, leading tau experts from around the world convened for the first‐ever Tau2020 Global Conference in Washington, DC, co‐organi...

Mindfulness-based programs (MBPs) are increasingly utilized to improve mental health. Interest in the putative effects of MBPs on cognitive function is also growing. This is the first meta-analysis of objective cognitive outcomes across multiple domains from randomized MBP studies of adults. Seven databases were systematically searched to January 2...

Introduction: White matter hyperintensities (WMH) are often described in Alzheimer's disease (AD), but their topography and specific relationships with cognition remain unclear. Methods: Regional WMH were estimated in 54 cognitively impaired amyloid beta-positive AD (Aβpos-AD), compared to 40 cognitively unimpaired amyloid beta-negative older co...

Objective The hippocampus is connected to 2 distinct cortical brain networks, the posterior–medial and the anterior–temporal networks, involving different medial temporal lobe (MTL) subregions. The aim of this study was to assess the functional alterations of these 2 networks, their changes over time, and links to cognition in Alzheimer's disease....

Dual-phase [¹⁸F]AV45 positron emission tomography (PET) is highly promising in the assessment of neurodegenerative diseases, allowing to obtain information on both neurodegeneration (early-phase; eAV45) and amyloid deposition (late-phase; lAV45) which are highly complementary; yet eAV45 needs further evaluation. This study aims at validating eAV45...

Over the past 25 years, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, there are no reference standards against which to anchor measures of individual differences in brain morphology, in contrast to growth charts for traits such as height and weight. Here, we built an interactive online...

Introduction: Older adults experiencing subjective cognitive decline (SCD) have a heightened risk of developing dementia and frequently experience subclinical anxiety, which is itself associated with dementia risk. Objective: To understand whether subclinical anxiety symptoms in SCD can be reduced through behavioral interventions. Methods: SCD...

Objectives: Deepening our understanding of the mechanisms by which meditation practices impact well-being and human flourishing is essential for advancing the science of meditation. The phenomenologically grounded classification system introduced by Dahl, Lutz, and Davidson (2015) distinguishes attentional, constructive, and deconstructive forms of...

Background: We classified non-demented European Prevention of Alzheimer's Dementia (EPAD) participants through the amyloid/tau/neurodegeneration (ATN) scheme and assessed their neuropsychological and imaging profiles. Materials and methods: From 1500 EPAD participants, 312 were excluded. Cerebrospinal fluid cut-offs of 1000 pg/mL for amyloid bet...

Objective To investigate, in Korsakoff patients (KS), cognitive and brain changes over months and up to 10 years after the diagnosis. Methods Two groups of 8 KS patients underwent neuropsychological, motor and neuroimaging investigations including structural MRI and ¹⁸ F-FDG-PET. The KS C group was examined early after the KS diagnosis (KS C -T1)...

Background and Purpose The in vivo diagnosis of cerebral amyloid angiopathy (CAA) is currently based on the Boston criteria, which largely rely on hemorrhagic features on brain magnetic resonance imaging. Adding to these criteria ¹⁸ F-fluoro-deoxy-D-glucose (FDG) positron emission tomography, a widely available imaging modality, might improve their...

Measures of resting-state functional connectivity allow the description of neuronal networks in humans and provide a window on brain function in normal and pathological conditions. Characterizing neuronal networks in animals is complementary to studies in humans to understand how evolution has modelled network architecture. The mouse lemur (Microce...

Background As the population ages, maintaining mental health and well-being of older adults is a public health priority. Beyond objective measures of health, self-perceived quality of life (QoL) is a good indicator of successful aging. In older adults, it has been shown that QoL is related to structural brain changes. However, QoL is a multi-facete...

Understanding the role of neuromodulators of socio-affective processing is important to ensure psychological wellbeing during older years. Here, we investigated the link between blood serotonin levels and brain and behavioral responses to emotional information in healthy elderly. A priori regions of interest (ROI) were selected due to their role in...

Background White matter hyperintensities (WMH) are frequently found in Alzheimer’s disease (AD). Commonly considered as a marker of cerebrovascular disease, regional WMH may be related to pathological hallmarks of AD, including beta-amyloid (Aβ) plaques and neurodegeneration. The aim of this study was to examine the regional distribution of WMH ass...

Ageing is characterized by a progressive decline of sleep quality. Sleep difficulties are increasingly recognized as a risk factor for Alzheimer’s disease (AD), and have been associated with cognitive decline. However, the brain substrates underlying this association remain unclear. In this review, our objective was to provide a comprehensive overv...

White matter hyperintensities (WMH) are a frequent marker of cognitive impairment and Alzheimer’s disease (AD). Although WMH have been commonly linked to cerebrovascular disease, recent studies suggest an association between AD pathology and regional WMH distribution. The objective of this study was to investigate the relationship of AD neuroimagin...

The medial temporal lobe (MTL, i.e. hippocampus and adjacent cortices) is particularly vulnerable to age‐related diseases: Alzheimer’s disease, other age‐related proteinothies (TDP‐43, AGD, etc) and vascular injury. Yet, the subregional pattern of vulnerability is thought to differ across etiologies; characterizing these differences using high‐reso...