Gaël Chételat

Unité Inserm U1077

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013–2022), the first ten-year stage of the lifespan CCNP (2013–2032), is a two-stages project focus...

Importance: Nonpharmacological interventions are a potential strategy to maintain or promote cognitive functioning in older adults. Objective: To investigate the effects of 18 months' meditation training and 18 months' non-native language training on cognition in older adults. Design, setting, and participants: This study was a secondary analy...

Background APOE4 is the main genetic risk factor for Alzheimer’s disease (AD). Recent findings suggest that lifestyle factors could modulate the association between APOE4 and cognitive impairment and/or dementia risk. However, a comprehensive assessment of the interactions between lifestyle and APOE4 status on neuroimaging and cognitive markers of...

Background Allostatic load (AL) is a cumulative measure of dysregulations across multiple physiological systems of the body occurring over time. AL was originally developed to explain how chronic stress damages physiologic systems and accelerates aging. Studies exploring the relationship between AL and brain health in older adults using a multimoda...

Background and objectives Sleep-disordered breathing (SDB) has been related to amyloid deposition and increased dementia risk. However, how SDB relates to medial temporal lobe neurodegeneration and subsequent episodic memory impairment is unclear. Our objective was to investigate the impact of amyloid positivity on the associations between SDB seve...

Objective: Self-perceived cognitive functioning, considered highly relevant in the context of aging and dementia, is assessed in numerous ways-hindering the comparison of findings across studies and settings. Therefore, the present study aimed to link item-level self-report questionnaire data from international aging studies. Method: We harmoniz...

Background: Alzheimer’s disease (AD) and Korsakoff’s syndrome (KS) are two major neurocognitive disorders characterized by amnesia but AD is degenerative while KS is not. The objective is to compare regional volume deficits within the Papez circuit in AD and KS, considering AD progression. Methods: 18 KS patients, 40 AD patients (20 with Moderate A...

Background and objectives Studies are sparse regarding the association between the informant-reported subjective memory decline (informant-report) and Alzheimer’s disease (AD) biomarkers. This study thus aimed at determining the clinical relevance of the informant-report throughout the AD clinical continuum, by assessing its specific relationships...

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...

White matter hyperintensities (WMH), frequently seen in older adults, are usually considered vascular lesions, and participate in the vascular contribution to cognitive impairment and dementia. However, emerging evidence highlights the heterogeneity of WMH pathophysiology, suggesting that non-vascular mechanisms could also be involved, notably in A...

Medial temporal lobe (MTL) subregions are differentially affected in Alzheimer's disease (AD), with a specific involvement of the entorhinal cortex (ERC), perirhinal cortex and hippocampal cornu ammonis (CA)1. While amyloid (Aβ) and APOEε4 are respectively the first molecular change and the main genetic risk factor in AD, their links with MTL atrop...

Amyloid-β accumulation starts in highly connected brain regions and is associated with functional connectivity alterations in the early stages of Alzheimer’s disease. This regional vulnerability is related to the high neuronal activity and strong fluctuations typical of these regions. Recently, dynamic functional connectivity was introduced to inve...

Observational population studies indicate that prevention of dementia and cognitive decline is being accomplished, possibly as an unintended result of better vascular prevention and healthier lifestyles. Population aging in the coming decades requires deliberate efforts to further decrease its prevalence and societal burden. Increasing evidence sup...

Objectives Aging people experience a slight decrease in their cognitive efficiency, even in the absence of brain pathology. Concurrently, several studies have reported positive effects of meditation practice on older adults’ cognitive functioning. This study aimed to assess if dispositional mindfulness (or more generally trait meditation capacities...

Objective: Rapid-eye-movement (REM) sleep is markedly altered in Alzheimer's disease (AD), and its reduction in older populations is associated with AD risk. However, little is known about the underlying brain mechanisms. Our objective was to investigate the relationships between REM sleep integrity and amyloid deposition, grey matter volume and p...

Basic emotional functions seem well preserved in older adults. However, their reactivity to and recovery from socially negative events remain poorly characterized. To address this, we designed a ‘task–rest’ paradigm in which 182 participants from two independent experiments underwent functional magnetic resonance imaging while exposed to socio-emot...

Early amyloid deposition results in functional and structural brain alterations in predementia stages of Alzheimer's disease (AD). However, how early functional and structural brain changes are related to each other remains unclear. Investigating the simultaneous disruptions of functional‐structural brain features within individuals in relation to...

The medial temporal lobe (MTL) is extensively connected to the rest of the brain through two specific networks which are particularly affected in Alzheimer’s disease (AD): the anterior‐temporal (AT) and posterior‐medial (PM) systems. As the specific and respective effects of age and sex on the functional integrity of these networks are still largel...

Early amyloid deposition results in functional and structural brain alterations in predementia stages of Alzheimer's disease (AD). However, how early functional and structural brain changes are related to each other remains unclear. Investigating the simultaneous disruptions of functional‐structural brain features within individuals in relation to...

In preclinical Alzheimer’s disease (AD), amyloid accumulates in highly‐functionally connected brain regions. This selective vulnerability is related to the high neuronal fluctuations, typical of these regions. Dynamic functional connectivity (FC) was introduced to investigate network organization over time, with high network variations indicating r...

In preclinical Alzheimer’s disease (AD), amyloid accumulates in highly‐functionally connected brain regions. This selective vulnerability is related to the high neuronal fluctuations, typical of these regions. Dynamic functional connectivity (FC) was introduced to investigate network organization over time, with high network variations indicating r...

Allostatic load (AL) is a cumulative measure of dysregulations across multiple physiological systems of the body occurring over time. AL was originally developed to explain how chronic stress damages physiologic systems and accelerates aging. Studies exploring the relationship between AL and brain health in older adults using a multimodal approach...

The medial temporal lobe (MTL) is extensively connected to the rest of the brain through two specific networks which are particularly affected in Alzheimer’s disease (AD): the anterior‐temporal (AT) and posterior‐medial (PM) systems. As the specific and respective effects of age and sex on the functional integrity of these networks are still largel...

APOE4 is the main genetic risk factor for Alzheimer’s disease (AD). Recent findings suggest that lifestyle factors could modulate the association between APOE4 and cognitive impairment and/or dementia risk. However, a comprehensive assessment of the interactions between lifestyle and APOE4 status on neuroimaging and cognitive markers of aging and A...

Brain‐age can be inferred from structural neuroimaging and compared to chronological age (brain‐age delta), as a marker of accelerated/decelerated biological brain aging. Accelerated biological aging has been found in Alzheimer’s disease (AD), but validation against biomarkers of AD and neurodegeneration is lacking. We studied the association betwe...

Sleep plays a crucial role in memory consolidation. Recent data in rodents and young adults revealed that fast spindle band power fluctuates at a 0.02-Hz infraslow scale during non-rapid eye movement (NREM) sleep. These fluctuations result from a periodic temporal clustering of spindles and may modulate sleep maintenance and memory consolidation. W...

Objectives: As the world population is ageing, it is vital to understand how older adults can maintain and deepen their psychological well-being as they are confronted with the unique challenges of ageing in a complex and vulnerable world. Theoretical work has highlighted the promising role of intentional mental training such as meditation practice...

Objectives To compare regional volume deficits within the Papez circuit in Alzheimer’s disease (AD) and Korsakoff’s syndrome (KS), taking into account the neurodegenerative nature of AD. Methods 18 KS patients, 40 AD patients (20 with Moderate AD (MAD) matched on cognitive deterioration with KS patients and 20 with Severe AD (SAD)), and 70 healthy...

Subclinical depressive symptoms are associated with increased risk of Alzheimer’s disease (AD), but the brain mechanisms underlying this relationship are still unclear. We aimed to provide a comprehensive overview of the brain substrates of subclinical depressive symptoms in cognitively unimpaired older adults using complementary multimodal neuroim...

Importance: No lifestyle-based randomized clinical trial directly targets psychoaffective risk factors of dementia. Meditation practices recently emerged as a promising mental training exercise to foster brain health and reduce dementia risk. Objective: To investigate the effects of meditation training on brain integrity in older adults. Design...

Objectives Older adults with subjective cognitive decline (SCD) recruited from memory clinics have an increased risk of developing dementia and regularly experience reduced psychological well-being related to memory concerns and fear of dementia. Research on improving well-being in SCD is limited and lacks non-pharmacological approaches. We investi...

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...

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,...

Background Sleep‐dependent memory consolidation, which is thought to rely on the dialogue between the hippocampus and the medial prefrontal cortex (mPFC) during NREM sleep, is mediated by slow waves (SW) and sleep spindles. Some studies indicate that this process is impaired in ageing but also in sleep‐disordered breathing (SDB), a very common slee...

Background 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...

Background 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. Th...

Background 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 S...

Background 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...

Background 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) includ...

Background 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...

Background 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...

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...

Background Physical inactivity in older adults has been linked to an increased risk of dementia. On the other hand, increasing evidence indicates that sex is likely to influence Alzheimer’s disease (AD) pathophysiology, leading to a differential susceptibility to the disease in women versus men. We propose to investigate the interplay between sex a...

Background 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 period...

Background 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., recov...

Background 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 m...

Background 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...

Background 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 stud...

Background 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...

Background 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‐tau...

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...