Natalie L Marchant

• PhD
• Associate Professor at University College London

We propose the concept of Cognitive Debt to characterize thoughts and behaviors that increase vulnerability to symptomatic Alzheimer's disease (AD). Evidence indicates that depression, anxiety, sleep disorder, neuroticism, life stress, and post-traumatic stress disorder increase risk for AD, and we suggest they do so by increasing Cognitive Debt. R...

Objectives Anxiety is an increasingly recognised predictor of cognitive deterioration in older adults and in those with mild cognitive impairment. Often believed to be a prodromal feature of neurodegenerative disease, anxiety may also be an independent risk factor for dementia, operationally defined here as preceding dementia diagnosis by ≥10 years...

Introduction: The Cognitive Debt hypothesis proposes that repetitive negative thinking (RNT), a modifiable process common to many psychological risk factors for Alzheimer's disease (AD) may itself increase risk. We sought to empirically examine relationships between RNT and markers of AD, compared with anxiety and depression symptoms. Methods: T...

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...

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 Minoritized ethnic populations are underrepresented in dementia research despite having differing risk and prognosis profiles. We sought to gain multiperspective insights about why minoritized ethnic groups are underrepresented in dementia research. METHODS Qualitative data were collected from focus groups with individuals from minori...

Introduction Allostatic load (AL) is a composite score of progressive physiological dysregulations in response to long-term exposure to everyday stress. Despite growing interest, limited research has focused on links with cerebral and cognitive aspects of aging and with markers sensitive to Alzheimer’s disease (AD) in a healthy elderly population a...

BACKGROUND Digital biomarkers are gaining interest as proxy markers for mental health as they enable passive and continuous data collection. However, the association between digital biomarkers of health and anxiety, both generalised anxiety disorder and anxiety symptoms, remains unknown. OBJECTIVE This systematic review and meta-analysis aimed to...

Purpose of review This review focuses on the role of psychological factors in cognitive aging and dementia, an area that has received less attention compared to other modifiable factors (e.g. sleep, physical activity, and so on) or reduction of disease risk. Recent findings A range of mental health and psychological aspects, including clinical sym...

Question: What is the current evidence base for the association between digital biomarkers from wrist-worn wearables, loneliness and social isolation in adults? Study selection and analysis: We systematically searched six databases from inception to 24th September, 2024. We narratively synthesised findings and pooled effect sizes using random-effec...

Background Despite evidence that sex can modulate Alzheimer’s disease (AD) risk, whether risk factors are similarly related to AD markers in women and men remains largely unexplored. We aimed to assess how a combination of potentially modifiable risk factors are associated with cognitive and pathological markers of AD in older women and men. Metho...

Background Anxiety, both generalised anxiety disorder and anxiety symptoms, has been recognised as a risk factor and prodromal symptom of dementia. Digital biomarkers are gaining interest as proxy markers for mental health because they enable passive and continuous data collection, allowing for early detection. However, the association between digi...

Background Despite evidence that sex can modulate Alzheimer’s disease (AD) risk, whether risk factors are similarly related to AD markers in women and men remains largely unexplored. We aimed to assess how a combination of potentially modifiable risk factors are associated with cognitive and pathological markers of AD in older women and men. Metho...

Background Social isolation, encompassing factors like living alone and limited social contact, is associated with increased risk of Alzheimer’s disease (AD). One theory is that loneliness, which is the negative psychological affect often associated with social isolation, mediates the relationship between social isolation and AD. Mendelian randomiz...

Background Alzheimer's disease (AD) is a complex disorder with a strong genetic component, yet many genetic risk factors remain unknown. Integrating genome‐wide association studies (GWAS) and high‐throughput proteomic platforms is a useful strategy to evaluate protein quantitative trait loci (pQTLs) and to detect candidate genes and pathways involv...

Background Increased stress, a proposed risk factor for Alzheimer’s disease (AD), is associated with increased brain and cognitive vulnerabilities in older populations, which may be different in women and men. Objective To examine cross‐sectional associations between circulating stress hormones (epinephrine, norepinephrine, cortisol, dehydroepiand...

Background: Subclinical depressive symptoms increase the risk of developing Alzheimer's disease (AD). The neurobiological mechanisms underlying this link may involve stress system dysfunction, notably related to the hippocampus which is particularly sensitive to AD. We aimed to investigate the links between blood stress markers and changes in brai...

Background Psychological factors such as repetitive negative thinking, proneness to experience distress, and perceived stress are associated with increased risk of neurodegeneration and clinical dementia, whereas having a sense of life‐purpose, self‐reflection, and dispositional mindfulness may be protective. However, whether combinations of these...

Psychological characteristics are associated with varying dementia risk and protective factors. To determine whether these characteristics aggregate into psychological profiles and whether these profiles differentially relate to aging health, we conducted a cross-sectional investigation in two independent middle-aged (51.4 ± 7.0 years (mean ± s.d.)...

High-throughput proteomic platforms are crucial to identify novel Alzheimer’s disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan® 7k) and antibody-based (Olink® Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona re...

Background Increased stress is a proposed risk factor for Alzheimer’s disease (AD). We examined cross-sectional associations between circulating stress biomarkers and multimodal measures of brain health and cognition susceptible to AD in older adults and sex-specific subgroups. Methods Baseline data from 132 cognitively unimpaired participants wit...

Meditation is a mental training approach that can improve mental health and well-being in aging. Yet the underlying mechanisms remain unknown. The Medit-Ageing model stipulates that three mechanisms — attentional, constructive, and deconstructive — upregulate positive psycho-affective factors and downregulate negative ones. To test this hypothesis,...

Emerging evidence suggests that repetitive negative thinking (RNT; i.e., worry and ruminative brooding) is associated with biomarkers of Alzheimer’s disease. Given that women have a greater risk of many neurodegenerative diseases, this study investigated whether worry and brooding are associated with general neurodegeneration and whether associatio...

Understanding the factors that predict why some individuals perceive to respond more to meditation training than others could impact the development, efficacy, adherence levels, and implementation of meditation-based interventions. We investigated individual-level variables associated with self- and teacher-perceived responsiveness to longer-term m...

INTRODUCTION People with dementia may benefit from psychological therapies for depression or anxiety, but evidence of their effectiveness in atypical dementia is limited. METHODS Using electronic health‐care records of > 2 million people who attended psychological therapy services in England between 2012 and 2019, we examined pre–post therapy symp...

Background Shorter telomeres are associated with increased risk of cognitive decline and age-related diseases. Developing interventions to promote healthy aging by preserving telomere integrity is of paramount importance. Here, we investigated the effect of an 18-month meditation intervention on telomere length (TL) measures in older people without...

The COVID-19 pandemic significantly challenged mental health of populations worldwide. We aimed to assess changes in mental health of cognitively unimpaired (CU) older adults with pre-existing subclinical depressive symptoms during pandemic-related confinements, and the factors that could modulate these changes. CU older adults with (DepS, n=53) an...

BACKGROUND: Subclinical depressive symptoms increase the risk of developing Alzheimer’s disease (AD). The neurobiological mechanisms underlying this link may involve stress system dysfunction, notably related to the hippocampus which is particularly sensitive to AD. We aimed to investigate the links between blood stress markers and changes in brain...

High-throughput proteomic platforms have a crucial role in identifying novel Alzheimer's disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan® 7k) and antibody-based (Olink® Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center B...

Aging is associated with cognitive changes, even in the absence of brain pathology. This study aimed to determine if meditation training, by comparison to active and passive control groups, is linked to changes in the perception of cognitive functioning in older adults. One hundred thirty-four healthy older participants from the Age-Well Randomized...

Introduction Mental health conditions are associated with cognition and physical function in older adults. We examined whether worry and ruminative brooding, key symptoms of certain mental health conditions, are related to subjective and/or objective measures of cognitive and physical (cardiovascular) health. Methods We used baseline data from 282...

Background The research criteria for subjective cognitive decline (SCD) exclude mild cognitive impairment (MCI), but do not stipulate the use of specific MCI criteria. This study compared different approaches to defining (i.e., excluding) MCI during the ascertainment of SCD, focusing on the impact on dementia incidence rates in SCD. Methods This c...

Emerging evidence suggests that Repetitive Negative Thinking (RNT; i.e., worry and ruminative brooding) is associated with biomarkers of Alzheimer’s disease. However, it is neither known whether RNT may be a marker of neurodegenerative disease more generally, nor the mechanism through which RNT may act. Given that women have greater risk of many ne...

INTRODUCTION Older adults experiencing subjective cognitive decline (SCD) have a higher risk of dementia. Reducing this risk through behavioral interventions, which can increase emotional well‐being (mindfulness and compassion) and physical activity, is crucial in SCD. METHODS SCD‐Well is a multicenter, observer‐blind, randomized, controlled, supe...

Objective Poor sleep and high levels of repetitive negative thinking (RNT), including future-directed (ie, worry) and past-directed (ie, brooding) negative thoughts, have been associated with markers of dementia risk. The relationship between RNT and sleep health in older adults is unknown. This study aimed to investigate this association and its s...

Background Psychological therapies can be effective in reducing symptoms of depression and anxiety in people living with dementia (PLWD). However, factors associated with better therapy outcomes in PLWD are currently unknown. Aims To investigate whether dementia-specific and non-dementia-specific factors are associated with therapy outcomes in PLW...

Background High‐throughput proteomic platforms are an useful strategy to detect novel biomarkers and pathways involved in Alzheimer’s disease (AD) development. Due to the novelty of these techniques, an extensive quality control assessment is needed to ensure the reliability of those protein measurements. In this study, we aimed to assess the repro...

Background Recent evidence in Alzheimer’s diseases suggests that early dysfunction of emotional processing may precede the onset of cognitive decline and dementia. Altered functional brain connectivity patterns also occur along with other brain changes many years before clinical AD symptoms. Method We combined baseline multimodal neuroimaging data...

Background Age is the strongest risk factor for dementia, including Alzheimer’s disease (AD). However, across individuals of the same chronological age there is considerable heterogeneity in rates of cognitive decline. These differences have been attributed to individual differences in age‐related biological processes, including brain protein expre...

Background Repetitive Negative Thinking (RNT) includes negative thoughts about the future (worry) and past (ruminative brooding). RNT has been associated with Alzheimer’s disease (AD) pathology (Marchant et al. Alzheimers Dement . 2020;16(7)) and different patterns of functional connectivity of the triple network of attention, namely, the default m...

Background Primary care psychological therapy services can be effective in reducing symptoms of depression and anxiety in people living with dementia (PLWD) and are recommended in national guidelines (e.g., NICE, UK). However, it is currently unknown which factors are associated with better psychological therapy outcomes in PLWD. Method National l...

Background Positive and negative psychological factors represent pertinent moderators of relative risk and protection for cognitive decline and dementia. For example, repetitive negative thinking has been associated with accelerated cognitive decline and AD pathology ¹ , whereas self‐reflection and purpose in life have been related to better cognit...

Background Subclinical depressive symptoms are associated with increased risk of Alzheimer’s disease (AD). This link could be related to stress system dysfunction, known to occur in both depression and AD, and to depend notably on the hippocampus which is particularly sensitive to AD. We aimed at investigating the links between levels of blood stre...

Background Depression and anxiety are well recognised as risk factors for dementia and poorer cognitive outcomes. However, considerably less is known about the relationship between quality of life and cognitive function over time. Quality of life is not simply the absence of mental health problems, but instead is a related but distinct construct. I...

Background Non‐pharmacological interventions are a potential strategy to maintain or promote cognitive functioning in older adults. We investigated the effects of 18‐months meditation or non‐native language training versus no intervention on cognition in older adults. Method Age‐Well was an observer‐blind, randomised, controlled clinical trial wit...

Background Nearly half of people aged 60+ experience memory impairments that infer an increased risk of dementia. The UK APPLE‐Tree (Active Prevention in People at risk of dementia through Lifestyle, bEhaviour change and Technology to build REsiliEnce) trial is evaluating a secondary dementia prevention intervention for people at increased dementia...

Background Anxiety has been identified as both a risk factor and prodromal symptom for Alzheimer’s disease (AD) and related dementias, however, the underlying neurobiological correlates remain unknown. The aim of this systematic review and meta‐analysis was to examine the association between anxiety symptoms and two defining markers of AD neuropath...

Background Subclinical depressive symptoms are associated with increased risk of Alzheimer’s disease (AD). This link could be related to stress system dysfunction, known to occur in both depression and AD, and to depend notably on the hippocampus which is particularly sensitive to AD. We aimed at investigating the links between levels of blood stre...

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...

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 world. Theoretical work has highlighted the promising role of intentional mental training such as meditation practice for enhancing h...

Sleep, especially slow wave sleep (SWS), is essential for cognitive functioning and is reduced in aging. The impact of sleep quality on cognition is variable, especially in aging. Cognitive reserve (CR) may be an important modulator of these effects. We aimed at investigating this question to better identify individuals in whom sleep disturbances m...

Objectives To systematically review the association between traumatic life events (TLE) and dementia risk. Design Systematic review and meta-analysis. Data sources APA, PsychINFO, Embase and MEDLINE from their inception to 29.05.21 and updated on 20.04.22. Eligibility criteria for selecting studies Original research articles published in peer re...

Epidemiological studies show that modifiable risk factors account for about 40% of the population variability in risk of developing dementia, including sporadic Alzheimer's disease (sAD). Recent findings suggest that these factors might also modify disease trajectories of people with autosomal dominant Alzheimer's disease (ADAD). With positron emis...

INTRODUCTION: APOE4 genotype and lifestyle have been associated with Alzheimer's disease (AD) risk, but how they interact on neuroimaging and cognitive markers of aging and AD remains unclear. METHODS: In 135 cognitively unimpaired older adults from the baseline Age-Well trial, we investigated the interaction between APOE4 status and cognitive acti...

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...

Persistent fatigue constitutes a prevalent and debilitating symptom in several diseases. The symptom is not effectively alleviated by pharmaceutical treatments, and meditation has been proposed as a non-pharmacological intervention. Indeed, meditation has been shown to reduce inflammatory/immune problems, pain, stress, anxiety and depression which...

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 Repetitive Negative Thinking (RNT) includes negative thoughts about the future (worry) and past (rumination), and has been associated with AD physiopathology (Marchant et al. Alzh&Dement 2020;16:1054). Prefrontal and anterior cingulate cortices play a major role in RNT (Demnitz‐King et al., Psychiatry Res Neuroimaging. 2021;316:111353)....

Background Individuals with subjective cognitive decline (SCD) perceive that their cognition has worsened, but score normally on standardized cognitive tests. It is increasingly recognized that SCD has variable prognosis with the risk of progression to dementia being twice that of age‐matched controls without SCD. This study aimed to characterize a...

Aims: People with depression are up to 72% more at risk to develop cardiovascular disease (CVD) in their lifetime. Evidence-based psychotherapies are first-line interventions for the treatment of depression and are delivered nationally in England through the National Health Service via the Improving Access to Psychological Therapy (IAPT) primary c...

Objective: Anxiety has been identified as both a risk factor and prodromal symptom for Alzheimer's disease (AD) and related dementias, however, the underlying neurobiological correlates remain unknown. The aim of this systematic review and meta-analysis was to examine the association between anxiety symptoms and two defining markers of AD neuropat...

Background Dementia incidence is increasing across the globe and currently there are no disease-modifying pharmaceutical treatments. The Lancet Commission on dementia identified 12 modifiable risk factors which explain 40% of dementia incidence. However, whether these associations are causal in nature is unclear. Objective To examine the modifiabl...

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...

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...

Background Meta-analyses support an association between anxiety in older adulthood and dementia. The aim of this study was to use routinely collected health data to test whether treatment of anxiety disorders through psychological intervention is associated with a lower incidence of dementia. Methods In this prospective cohort study, data from nat...

Background Repetitive Negative Thinking (RNT) includes negative thoughts about the future and past, and is a risk factor for depression and anxiety. Prefrontal and anterior cingulate cortices have been linked to RNT but several regions within large-scale networks are also involved, the efficiency of which depends on their ability to remain segregat...

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...

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...

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...

Background Depression is an important, potentially modifiable dementia risk factor. However, it is not known whether effective treatment of depression through psychological therapies is associated with reduced dementia incidence. The aim of this study was to investigate associations between reduction in depressive symptoms following psychological t...

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...

Background Older individuals with subjective cognitive decline (SCD) perceive that their cognition has declined but do not show objective impairment on neuropsychological tests. Individuals with SCD are at elevated risk of objective cognitive decline and incident dementia. Non-pharmacological interventions (including mindfulness-based and health se...

Background Large-scale trials of multidomain interventions show that modifying lifestyle and psychological risk factors can slow cognitive decline. We aim to determine if a lower intensity, personally tailored secondary dementia prevention programme for older people with subjective or mild objective memory decline, informed by behaviour change theo...

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...

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...

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...

The primary aim of this study was to investigate the relationship between meditation experience and repetitive negative thinking (RNT) in regular meditators with a wide range of experience, and to examine the extent to which self-compassion and mindfulness mediate this relationship. RNT is a transdiagnostic process that is implicated in the develop...

Affective disorders are associated with accelerated cognitive ageing. However, current understanding of biological mechanisms which underlie these observed associations is limited. The aim of this study was to test: 1) Whether cortisol acts as a pathway in the association between depressive or anxiety symptoms across adulthood and midlife cognitive...

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...

BACKGROUND Mindfulness, defined as non-judgmental awareness of the present moment, has been associated with an array of mental and physical health benefits. Mindfulness may also represent a protective factor for Alzheimer’s disease (AD). Here, we tested the potential protective effect of trait mindfulness on cognitive decline and AD pathology in ol...

There is an urgent need to improve the understanding of neuroinflammation in Alzheimer’s disease (AD). We analyzed cerebrospinal fluid inflammatory biomarker correlations to brain structural volume and longitudinal cognitive outcomes in the DELCODE study and in a validation cohort of the F.ACE Alzheimer Center Barcelona. We investigated whether res...

Background Largescale trials of multi-domain interventions show that modifying lifestyle and psychological risk factors can slow cognitive decline. We aim to determine if a lower intensity, personally tailored secondary dementia prevention programme for older people with subjective or mild objective memory decline, informed by behaviour change theo...

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 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 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...