Nikolaos Scarmeas

• Columbia University

Diet shapes immune function and disease susceptibility, yet the underlying mechanisms remain poorly defined. Here, we investigated the immunometabolic effects of short-term dietary restriction of animal products in a unique group of Greek individuals who alternate between omnivory and animal product restriction for religious reasons. We profiled cl...

Introduction Anti-amyloid antibodies for the treatment of Alzheimer´s disease (AD) are currently being evaluated for approval and reimbursement in Europe. An approval brings opportunities, but also challenges to health care systems across Europe. The objective of this position paper is to provide guidance from experts in the field in terms of navig...

Among the more than 90 identified genetic risk loci for late-onset Alzheimer′s disease (AD) and related dementias, the apolipoprotein E gene (APOE) ϵ2/ϵ3/ϵ4 polymorphism remains the longstanding benchmark for genetic disease risk with a consistently large effect across studies. Despite this massive signal, the exact mechanisms for how ϵ4 increases...

Cerebrospinal fluid (CSF) amyloid beta (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau181) are well accepted markers of Alzheimer’s disease. We performed a GWAS meta-analysis including 18,948 individuals of European and 416 non-European ancestry. We identified 12 genome-wide significant loci across all three biomarkers, eight of them novel...

Introduction: Neurodegenerative diseases like progressive supranuclear palsy (PSP) present challenges concerning their diagnosis. Neuroimaging using magnetic resonance (MRI) may add diagnostic value. However, modern techniques such as volumetric assessment using Voxel-Based Morphometry (VBM), although proven to be more accurate and superior compare...

Purpose According to a WHO statement, it has been asserted that there is no safe level of alcohol consumption regarding human health. Nevertheless, the relationship between alcohol consumption and Alzheimer’s disease (AD) pathology remains unclear. Therefore, we examined whether the frequency and patterns of alcohol consumption could predict neurod...

As sleep appears to be closely related to cognitive status, we aimed to explore the association between the percentage of deep sleep, cognitive state, and the cerebrospinal fluid (CSF) biomarker amyloid-beta 42 in non-demented individuals. In this cross-sectional study, 90 non-demented participants from the Aiginition Longitudinal Biomarker Investi...

Depressive symptoms are common in mild cognitive impairment (MCI), dementia caused by Alzheimer’s disease (AD dementia) and in cognitively unimpaired older adults. However, it is unclear whether they could contribute to the identification of cognitive impairment in ageing. To assess the potential utility of depressive symptoms to distinguish betwee...

Identifying individuals at-risk for dementia is one of the critical objectives of current research efforts, highlighting the need for simple, cost-effective, and minimally invasive biomarkers. Mild behavioral impairment (MBI), characterized by the emergence of persistent neuropsychiatric manifestations in older adults, has attracted increasing atte...

Importance Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology. Objective To examine the association between depressive symptoms...

In the present study, we investigated the association of genetic predisposition with specific dimensions of dementia pathophysiology for global and domain-specific cognitive decline in older adults. The sample was drawn from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) study, comprising 512 cognitively normal individuals over...

Objective Sleep disturbance is considered a risk factor for cognitive decline in elderly individuals. Our aim in the current study was to investigate whether baseline sleep parameters can predict the conversion from normal cognition to mild cognitive impairment or dementia at follow-up. The Hellenic Longitudinal Investigation of Aging and Diet is a...

Inflammation plays a major role in cognitive aging. Most studies on peripheral inflammation and cognitive aging focused on selected major inflammatory biomarkers. However, inflammatory markers are regulated and influenced by each other, and it is therefore important to consider a more comprehensive panel of markers to better capture diverse immune...

Background: There is a paucity of evidence on the association between genetic propensity for hippocampal atrophy with cognitive outcomes. Therefore, we examined the relationship of the polygenic risk score for hippocampal atrophy (PRShp) with the incidence of amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) as well as the rate...

Background Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralised clinical trials in dementia. There are many potential benefits associated with decentralised medication trials, but the field is currently lacking specific recommendations for their delivery in the deme...

Background Numerous studies have highlighted the role of oxidative stress in Alzheimer's disease (AD) development. Yet, the alignment of systemic and central oxidative stress biomarkers is unclear across diverse populations in the AD continuum. This study aims to assess protein damage levels in plasma and cerebrospinal fluid (CSF) within the AD con...

Background Oxidative stress has been implicated in the pathogenesis of Alzheimer’s disease (AD). Nevertheless, whether redox perturbations are associated with cognition and AD pathology in the preclinical AD stages, remains unclear. We examined associations of blood redox markers with AD biomarkers and cognitive performance in older adults without...

Background To estimate the additive associations of cardiometabolic multimorbidity (CMM) and depression on long‐term cognitive trajectory in multi‐regional cohorts and validate the generalizability of the findings in varying clinical settings. Method Data harmonization was performed across 14 longitudinal cohort studies within the Cohort Studies o...

Background Greece has among the largest proportions of elderly worldwide and is among the fastest aging countries in Europe. Consequently, the population suffering from mild cognitive impairment (MCI) or dementia is one of the largest in Europe. This population varies significantly within the different regions in Greece. Method We estimated the nu...

Background High‐income countries (HICs) are over‐represented in current global dementia incidence rates, skewing estimates. Variance in diagnostic methods between HICs and low‐ and middle‐income countries (LMICs) is speculated to contribute to the regional differences in rates. Cohort Studies of Memory in an International Consortium (COSMIC) offers...

Background Prior longitudinal studies have found that individuals born during World War II and the postwar period had lower incident dementia (Tom et al., 2020) than previous generations, a finding contradictory to research indicating early‐life stressors as adverse events for late‐life cognition. This study aimed to further explore this associatio...

Background Numerous studies have highlighted the role of oxidative stress in Alzheimer’s disease (AD) development. Yet, the alignment of systemic and central oxidative stress biomarkers is unclear across diverse populations in the AD continuum. This study aims to assess protein damage levels in plasma and cerebrospinal fluid (CSF) within the AD con...

Importance Baseline cerebral microbleeds (CMBs) and APOE ε4 allele copy number are important risk factors for amyloid-related imaging abnormalities in patients with Alzheimer disease (AD) receiving therapies to lower amyloid-β plaque levels. Objective To provide prevalence estimates of any, no more than 4, or fewer than 2 CMBs in association with...

Importance: Aging is accompanied by immune dysregulation, which has been implicated in Alzheimer's disease (AD) pathogenesis. Individuals who are genetically predisposed to elevated levels of proinflammatory mediators might be at increased risk for AD. Objective: To investigate whether genetic propensity for higher circulating levels of interleu...

Background The six global nutrition targets (GNTs) related to low birthweight, exclusive breastfeeding, child growth (ie, wasting, stunting, and overweight), and anaemia among females of reproductive age were chosen by the World Health Assembly in 2012 as key indicators of maternal and child health, but there has yet to be a comprehensive report o...

Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides a comprehensive assessment of health and risk factor trends at global, regional, national, and subnational levels. This study aims to examine the burden of diseases, injuries, and risk factors in the USA and highlight the disparities in health outcomes ac...

This appendix provides supplementary tables and figures for the paper titled “The burden of diseases, injuries, and risk factors by state in the USA, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021.”

Introduction Adjustable lifestyle factors, such as diet, are associated with cognitive functions, structural and functional brain measures, but the association between the functional connectivity (FC) and the Mediterranean Diet (Medicine) in population without dementia is yet to be explored. Methods The association between MeDi and brain FC in 105...

Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer’s Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-di...

Diet is a modifiable lifestyle factor with a proven role in cardiovascular disease risk reduction that might also play an important part in cognitive health. Evidence from observational studies has linked certain healthy dietary patterns to cognitive benefits. However, clinical trials of diet interventions have demonstrated either null or, at best,...

Background Over the past several decades, the overweight and obesity epidemic in the USA has resulted in a significant health and economic burden. Understanding current trends and future trajectories at both national and state levels is crucial for assessing the success of existing interventions and informing future health policy changes. We esti...

Methods appendix to: GBD 2021 US Obesity Forecasting Collaborators. National-level and state-level prevalence of overweight and obesity among children, adolescents, and adults in the USA, 1990–2021, and forecasts up to 2050. Lancet 2024; published online Nov 14. https://doi.org/10.1016/S0140-6736(24)01548-4. This appendix formed part of the origin...

Supplementary appendix 2. Results appendix to: GBD 2021 US Obesity Forecasting Collaborators. National-level and state-level prevalence of overweight and obesity among children, adolescents, and adults in the USA, 1990–2021, and forecasts up to 2050. Lancet 2024; published online Nov 14. https://doi.org/10.1016/S0140-6736(24)01548-4 This appendix...

Rare coding single nucleotide variants (SNV) and short insertions or deletions (indels) contribute to Alzheimer disease (AD) genetic risk, from pathogenic variants in autosomal dominant genes to risk factors with diverse effects. In contrast, copy number variants (CNV) have been scarcely studied, with the exception of a few autosomal dominant examp...

Background: There is paucity of evidence on the association of genetic propensity for hippocampal atrophy with cognitive outcomes. Therefore, we examined the relationship of a Polygenic Risk Score for hippocampal atrophy (PRShp) with the incidence of amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) as well as the rates of cogn...

Up-to-date estimates of stroke burden and attributable risks and their trends at global, regional, and national levels are essential for evidence-based health care, prevention, and resource allocation planning. We aimed to provide such estimates for the period 1990–2021. We estimated incidence, prevalence, death, and disability-adjusted life-year (...

Background: Up-to-date estimates of stroke burden and attributable risks and their trends at global, regional, and national levels are essential for evidence-based health care, prevention, and resource allocation planning. We aimed to provide such estimates for the period 1990–2021. Methods: We estimated incidence, prevalence, death, and disabilit...

Background Cardiometabolic multimorbidity (CMM) and depression are often co-occurring in older adults and associated with neurodegenerative outcomes. The present study aimed to estimate the independent and joint associations of CMM and depression on cognitive function in multi-regional cohorts, and to validate the generalizability of the findings i...

Background Sleep patterns often shift as people age, a phenomenon frequently associated with the onset of neurodegenerative conditions. Additionally, distinct alterations occur in brain structure as individuals grow older, particularly within the hippocampus, a region known for its role in cognition and sleep regulation. Yet, how exactly do changes...

(1) Background: Many studies link food intake with clinical cognitive outcomes, but evidence for brain biomarkers, such as memory-related limbic white matter (WM) tracts, is limited. We examined the association between food groups, limbic WM tracts integrity, and memory performance in community-dwelling individuals. (2) Methods: We included 117 non...

Background and objectives: Previous randomized controlled trials and longitudinal studies have indicated that ongoing antihypertensive use in late life reduces all-cause dementia risk, but the specific impact on Alzheimer dementia (AD) and non-AD risk remains unclear. This study investigates whether previous hypertension or antihypertensive use mo...

INTRODUCTION We investigated the associations of leptin markers with cognitive function and magnetic resonance imaging (MRI) measures of brain atrophy and vascular injury in healthy middle‐aged adults. METHODS We included 2262 cognitively healthy participants from the Framingham Heart Study with neuropsychological evaluation; of these, 2028 also h...

β-amyloid-targeting antibodies represent the first generation of effective causal treatment of Alzheimer’s disease (AD) and can be considered historical research milestones. Their effect sizes, side effects, implementation challenges and costs, however, have stimulated debates about their overall value. In this position statement academic clinician...

Estrogen exposure during menstrual years has been associated with late-life neuroprotection. We explored the presence of an age-sensitive menarche window for cognition in old age and the impact of socioeconomic status and education. We compared neuropsychological performance of 1082 older women [MeanAGE = 72.69 (5.48)] with menarche in childhood, e...

This study explores how social actors account for psychosocial barriers to healthcare access. Interviews with 17 residents in remote regions of Greece and 12 professionals employed by Mobile Medical Units were analyzed using the tools and concepts of critical discursive social psychology. Analysis indicated that, oriented to different accountabilit...

The emergence of sustained neuropsychiatric symptoms (NPS) among non-demented individuals in later life, defined as mild behavioral impairment (MBI), is linked to a higher risk of cognitive decline. However, the underlying pathophysiological mechanisms remain largely unexplored. A growing body of evidence has shown that MBI is associated with alter...

INTRODUCTION Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralized clinical trials in dementia. There are many potential benefits associated with decentralized medication trials, but we currently lack specific recommendations for their delivery in the dementia field....

INTRODUCTION: Recent growth in the functionality and use of technology has

Summary Background Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injur...

Background: Emerging observational evidence supports a role for higher fruit and vegetable intake in protecting against the development of depression. However, there is a scarcity of research in older adults or in low- to middle-income countries (LMICs). Methods: Participants were 7,801 community-based adults (mean age 68.6 ± 8.0 years, 55.8% fema...

Background Accurate assessments of current and future fertility-including overall trends and changing population age structures across countries and regions-are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to i...

This appendix provides detailed information on the methods for the paper “Global fertility in 204 countries and territories, 1950–2021 with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021”

Summary Background Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injur...

Objective: Our study aimed to explore whether physical condition might affect the association between genetic predisposition for Alzheimer's Disease (AD) and AD incidence. Methods: The sample of participants consisted of 561 community-dwelling adults over 64 years old, without baseline dementia (508 cognitively normal and 53 with mild cognitive imp...

The possible relationship between Subjective Cognitive Decline (SCD) and dementia needs further investigation. In the present study, we explored the association between specific biomarkers of Alzheimer’s Disease (AD), amyloid-beta 42 (Aβ42) and Tau with the odds of SCD using data from two ongoing studies. In total, 849 cognitively normal (CN) indiv...

Depression is the largest global contributor to non-fatal disease burden(1). A growing body of evidence suggests that dietary behaviours, such as higher fruit and vegetable intake, may be protective against the risk of depression(2). However, this evidence is primarily from high-income countries, despite over 80% of the burden of depression being e...

Gut microbiome composition has been associated with early preclinical Alzheimer’s disease (AD), as reflected by cerebrospinal fluid (CSF) amyloid beta pathology, and with mild cognitive impairment (MCI). However, the presence of distinct microbiota across different disease stages has not been fully characterized. We profiled gut microbiota in 50 no...

INTRODUCTION The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS We combined data from...

Background Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-base...

Background Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important follow...

The Child and Adolescent Mental Health Initiative (CAMHI) aims to enhance mental health care capacity for children and adolescents across Greece. Considering the need for evidence-based policy, the program developed an open-resource dataset for researching the field within the country. A comprehensive, mixed-method, community-based research was con...

Background: Restless legs syndrome/Willis–Ekbom disease (RLS/WED) has occasionally but not consistently been associated with cognitive and most notably language and executive impairment. The present study was conducted to investigate the cognitive trajectories of older individuals with RLS/WED. Methods: Participants were drawn from the randomly sel...

Background Accurate assessments of current and future fertility-including overall trends and changing population age structures across countries and regions-are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to i...

Background Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditio...

Background Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of D...

Subjective cognitive decline (SCD) has been described as a probable early stage of dementia, as it has consistently appeared to precede the onset of objective cognitive impairment. SCD is related to many risk factors, including genetic predisposition for dementia. The Apolipoprotein (APOE) ε4 allele, which has been thoroughly studied, seems to expl...

The clinical features and pathophysiology of neuropsychiatric symptoms (NPSs) in dementia have been extensively studied. However, the genetic architecture and underlying neurobiological mechanisms of NPSs at preclinical stages of cognitive decline and Alzheimer’s disease (AD) remain largely unknown. Mild behavioral impairment (MBI) represents an at...

Background:Good social connections are proposed to positively influence the course of cognitive decline by stimulating cognitive reserve and buffering harmful stress-related health effects. Prior meta-analytic research has uncovered links between social connections and the risk of poor health outcomes such as mild cognitive impairment, dementia, an...

Objective Normative data for older adults may be tainted by inadvertent inclusion of undiagnosed individuals at the very early stage of a neurodegenerative process. To avoid this pitfall, we developed norms for a cohort of older adults without MCI/dementia at 3-year follow-up. Methods A randomly selected sample of 1041 community-dwelling individua...

The present study investigated the association of genetic predisposition for white matter hyperintensities (WMHs) with incident amnestic mild cognitive impairment (aMCI) or Alzheimer’s disease (AD), as well as whether such an association was influenced by age, sex, and cognitive reserve. Overall, 537 individuals without aMCI or dementia at baseline...

Neuropsychiatric symptoms (NPS), including depression, anxiety, apathy, visual hallucinations, and impulse control disorders, are very common during the course of Parkinson’s disease (PD), occurring even at the prodromal and premotor stages. Mild behavioral impairment (MBI) represents a recently described neurobehavioral syndrome, characterized by...

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the “LIfestyle for BRAin health” (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for...

Objectives: To study (i) the prevalence of mild and moderate-to-severe depressive symptoms in the entire spectrum of cognitive ageing in Greece and (ii) the relationship between these symptoms and demographic and clinical data. Methods: The study was based on the randomly selected cohort of the Hellenic Longitudinal Investigation of Aging and Di...

Background Depression is a known risk factor for dementia, and social support may lower the risk of depression in older adults. There is, however, a lack of longitudinal analyses examining the association between emotional versus instrumental support and depressive symptoms in older adults. We analyzed the association of emotional and instrumental...

Current literature on the association between nutrition and cognitive function has focused mainly on total daily dietary intake of nutrients, foods or dietary patterns, while there has been much less focus on the timing of intake, i.e. the distribution of intake throughout the day and/or during specific eating occasions. Meal timing interferes with...

Background Depressive symptoms embody a risk factor for developing age‐related cognitive impairment, while they belong to the most common non‐cognitive symptoms of dementia. The conundrum of the prevalence of depressive symptoms in older adults in the Mediterranean region, but also worldwide is vividly reflected in reported prevalence rates ranging...

https://pubmed.ncbi.nlm.nih.gov/38092509/#full-view-affiliation-41

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is a multinational collaborative research study with >10,000 collaborators around the world. GBD generates a time series of summary measures of health, including prevalence, cause-specific mortality (CSMR), years of life lost (YLLs), years lived with disability (YLDs), and disabi...

Background: The aim of the present study was to investigate the association of prodromal PD (pPD) with trajectories of healthy aging, according to its latest definition by the WHO.Methods: In a sample of 1,226 older adults (704 women), PD diagnosis was reached through standard clinical research procedures. Probability of pPD was calculated accordin...

In the current review we provide a theoretical background on studies examining the association between sleep and brain function. We focus on the association between sleep and cognitive performance, cognitive changes over time and incident dementia as well. We then present some data on the link between sleep and subjective cognitive complaints, in p...

Background Some reports suggest that psychotic features may occur in the early stages of Parkinson’s disease (PD), but sensitive tools have not been utilized. Objective The aim was to evaluate the presence of psychotic symptoms using detailed scales and to assess the association with clinical characteristics. Methods Healthy controls and patients...