Jorge Jesús Llibre Guerra

• MD,MS
• Washington University in St. Louis

We conducted an in-depth longitudinal study on an individual carrying the presenilin 2 p.Asn141Ile mutation, traditionally associated with dominantly inherited Alzheimer's disease (AD), who has remarkably remained asymptomatic past the expected age of clinical onset. This study combines genetic, neuroimaging and biomarker analyses to explore the un...

We present a comprehensive global analysis of genetic variants associated with autosomal-dominant Alzheimer's disease (ADAD). A total of 550 variants in the APP, PSEN1, and PSEN2 genes were identified, of which 279 were classified as pathogenic or likely pathogenic based on ACMG-AMP criteria, utilizing data from the Dominantly Inherited Alzheimer N...

Background and Objectives While Hispanic/Latino populations in the U.S. are remarkably diverse in terms of birthplace and age at migration, we poorly understand how these factors are associated with cognitive aging. Our research seeks to operationalize a life course perspective of migration and health and contribute new understanding of Alzheimer’s...

Background Genetic testing for individuals with dominantly inherited Alzheimer’s disease (DIAD) is now of greater relevance due to the existence of therapeutic trials available to this population. However, the impact and main drivers influencing the decision to seek genetic testing are relatively unknown in Latin America (LatAm). Here we present re...

Background In autosomal dominant Alzheimer disease (ADAD), the position of a pathogenic genetic variant within the presenilin‐1 (PSEN1) coding sequence influences how amyloid‐beta accumulates and how dementia progresses (Joseph‐Mathurin et al, 2024). In the first trial of anti‐amyloid monoclonal antibodies in individuals at risk for ADAD (Dominantl...

Background Autosomal dominant Alzheimer disease (ADAD) is characterized by genetic mutations affecting the beta‐amyloid (Aß) pathway. However, vascular and immune factors play important roles which are not completely understood. Understanding the function of the neurovascular unit (NVU) comprised of neurons, glial cells, and vasculature, at differe...

Background Brain‐predicted age estimates are used to quantify an individual's brain age compared to a normative trajectory. We have recently shown that brain age from structural MRI is elevated in autosomal dominant Alzheimer disease (ADAD), a unique sample that allows the study of AD progression independently of age‐related confounds. Resting‐stat...

Background Amyloid‐plaque removal by monoclonal antibody therapies slows progression in symptomatic Alzheimer’s disease (AD), but effects on preventing the onset of symptoms and dementia in asymptomatic people with amyloid plaques are unknown. We report the final primary and secondary outcomes of the Dominantly Inherited Alzheimer Network Trials Un...

Background Amyloid‐related Imaging Abnormalities (ARIA) are side effects of beta‐amyloid plaque‐lowering monoclonal antibody drugs (APLmAbs). Understanding of ARIA mechanisms, risks, nature, evolution and optimal approaches to mitigation and management remains incomplete. Sporadic Alzheimer’s Disease (AD) trials support ARIA risk factors including...

Background Anti‐amyloid monoclonal antibody therapies have successfully removed amyloid plaque as measured using imaging techniques. However, the characteristic fluid biomarker trajectories following plaque removal remains understudied, particularly during the preclinical phases of disease. We investigated biomarker trajectories in the context of t...

Background Anti‐amyloid monoclonal antibody therapies for AD have documented plaque removal on amyloid PET scans. We evaluate the findings for amyloid PET, tau PET, FDG PET and volumetric MRI over the course the open label extension (OLE) for the DIAN‐TU gantenerumab treatment, compared to the last imaging obtained prior to the OLE (to evaluate for...

Background The double‐blind (DB) period of the DIAN–TU‐001 phase 3 trial with gantenerumab provided evidence of significant but incomplete reduction of amyloid plaques, cerebrospinal fluid total tau, and phospho‐tau181 in dominantly inherited Alzheimer’s disease (DIAD).¹Subsequently, eligible participants transitioned to an open‐label extension (OL...

Background The 2021 WHO report highlights the importance of global planning for dementia. Initiatives that unite and support young leaders and stakeholders from diverse backgrounds in dementia care & research are crucial. The G8 Summit on Dementia in 2013 led to the creation of the World Dementia Council and the World Young Leaders in Dementia (WYL...

Background While two‐thirds of the 57 million people with dementia worldwide live in low‐ and middle‐income countries, research to inform dementia‐related policy in these regions remains scarce. We aimed to increase early dementia diagnosis and the use of standardized cognitive assessment by PCP in primary care settings in Cuba Method We selected...

Background Cross‐national comparisons of dementia prevalence are essential for identifying unique determinants and cultural‐specific risk factors, but methodological differences in dementia ascertainment across countries hinder global comparisons. This study maps the 10/66 Dementia Research Group algorithm for dementia ascertainment, widely used an...

Background Brain‐predicted age estimates are used to quantify an individual's brain age compared to a normative trajectory. We have recently shown that brain age from structural MRI is elevated in autosomal dominant Alzheimer disease (ADAD), a unique sample that allows the study of AD progression independently of age‐related confounds. Resting‐stat...

Background Autosomal dominant Alzheimer disease (ADAD) is characterized by genetic mutations affecting the beta‐amyloid (Aβ) pathway. However, vascular and immune factors play important roles which are not completely understood. Understanding the function of the neurovascular unit (NVU) comprised of neurons, glial cells, and vasculature, at differe...

Background Cognitive reserve (CR) has emerged as a critical factor in understanding clinical‐cognitive heterogeneity in Alzheimer’s disease (AD). However, there is limited evidence of the effect of CR during asymptomatic phases of the disease, age at symptom onset (AAO) and longitudinal decline. In this study, we elucidate the impact of CR on AAO a...

Background Alzheimer’s disease and related dementias (ADRD) disproportionately affect Latinos compared to non‐Latino whites. Leveraging the non‐monolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aimed to determine contributors to ADRD dispariti...

Tau pathology in Alzheimer disease (AD) is often evaluated in regions associated with episodic memory impairment. However, heterogeneous spreading patterns of tau are observed and correspond to impairment in different cognitive domains. We have previously developed a metric to quantify tau spread extent that is robustly sensitive to atypical spread...

Hub regions in the brain, recognized for their roles in ensuring efficient information transfer, are vulnerable to pathological alterations in neurodegenerative conditions, including Alzheimer’s disease (AD). Computational simulations and animal experiments have hinted at the theory of activity-dependent degeneration as the cause of this hub vulner...

Objectives: Population ageing will lead to a dramatic increase in dementia prevalence globally. Recent evidence suggests a decline in dementia incidence in HIC due to increasing education levels and improvements in cardiovascular health. Although, most of the increase will occur in low and middle-income countries (LMICs), there are no recent estima...

Objectives: Leveraging the non-monolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aim to evaluate the relative contributions of SDoH and genetic ancestry in predicting dementia risk in Latin American populations Methods: Community-dwelling part...

Objectives: Because of the continued transition to older populations, various strategies have been developed to estimate the social impact and burden of health care. Regarding mental health, a strategy in the elderly is the measurement of neuropsychiatric symptoms (NPS), these include a wide range of behavioral and psychological manifestations. The...

Disease-modifying therapies for Alzheimer’s disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. H...

INTRODUCTION: Alzheimer disease (AD)-modifying therapies are approved for treatment of early-symptomatic AD. Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals. METHODS: Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for vario...

Background: Amyloid-plaque removal by monoclonal antibody therapies slows clinical progression in symptomatic Alzheimer disease (AD), however the potential for delaying the onset of clinical symptoms in asymptomatic people are unknown. We conducted a trial of gantenerumab to evaluate whether amyloid-plaque removal delays symptom onset and AD progre...

Background Little is known about the relationship between parkinsonism or Parkinson's disease (PD) and frailty in Latin America. Objective The study aimed to determine the cross‐sectional and prospective associations between parkinsonism and PD with frailty in a large multi‐country cohort in Latin America. Frailty was assessed using three differen...

Background and objectives: It remains unknown whether the associations between protective lifestyles and sporadic dementia risk reported in observational studies also affect age at symptom onset (AAO) in autosomal dominant Alzheimer disease (ADAD) with predominant genetic influences. We investigated the associations between resilience-related life...

In this high-throughput proteomic study of autosomal dominant Alzheimer’s disease (ADAD), we sought to identify early biomarkers in cerebrospinal fluid (CSF) for disease monitoring and treatment strategies. We examined CSF proteins in 286 mutation carriers (MCs) and 177 non-carriers (NCs). The developed multi-layer regression model distinguished pr...

This manuscript describes and summarizes the Dominantly Inherited Alzheimer Network Observational Study (DIAN Obs), highlighting the wealth of longitudinal data, samples, and results from this human cohort study of brain aging and a rare monogenic form of Alzheimers disease (AD). DIAN Obs is an international collaborative longitudinal study initiat...

INTRODUCTION Estimating treatment effects as time savings in disease progression may be more easily interpretable than assessing the absolute difference or a percentage reduction. In this study, we investigate the statistical considerations of the existing method for estimating time savings and propose alternative complementary methods. METHODS We...

INTRODUCTION Leveraging the nonmonolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aim to evaluate the relative contributions of SDoH and genetic ancestry in predicting dementia prevalence in Latin American populations. METHODS Community‐dwelli...

INTRODUCTION While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. METHODS In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and...

Approximately 5% of Alzheimer’s disease patients develop symptoms before age 65 (early-onset Alzheimer’s disease), with either sporadic (sporadic early-onset Alzheimer’s disease) or dominantly inherited (dominantly inherited Alzheimer’s disease) presentations. Both sporadic early-onset Alzheimer’s disease and dominantly inherited Alzheimer’s diseas...

This study explored the role of the ubiquitin-proteasome system (UPS) in dominantly inherited Alzheimer’s disease (DIAD) by examining changes in cerebrospinal fluid (CSF) levels of UPS proteins along with disease progression, AD imaging biomarkers (PiB PET, tau PET), neurodegeneration imaging measures (MRI, FDG PET), and Clinical Dementia Rating® (...

Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Al...

INTRODUCTION Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin‐1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre‐/postcodon 200) influences these pathologic features and dementia at different...

Background To date, there is no high throughput proteomic study in the context of Autosomal Dominant Alzheimers disease (ADAD). Here, we aimed to characterize early CSF proteome changes in ADAD and leverage them as potential biomarkers for disease monitoring and therapeutic strategies. Methods We utilized Somascan 7K assay to quantify protein level...

Background Studies suggest distinct differences in the development, presentation and longitudinal progression of Alzheimer’s Disease (AD) between women and men. However, most of these sex‐specific differences have been explored in symptomatic stages of sporadic AD. We investigated cross‐sectional sex differences in clinical‐cognitive assessments as...

Background Previous studies in the Cuban population suggest that Alzheimer’s Disease and related dementias (ADRD) are under‐diagnosed at primary care relative to population estimates. Recent interventions aimed to introduce the use of technology based cognitive assessments have been validated for primary care (e.g., Brain Health Assessment).However...

Background Autosomal dominant Alzheimer’s disease (ADAD) is caused by known genetic mutations that start a cascade of events leading to Aβ deposition, tau pathology and neurodegeneration. Mutation carriers (MCs) are characterized by substantial amyloid accumulation, and dementia onset at or around the age of parental dementia onset. CSF, plasma Aβ,...

Background Clinical presentation of dominantly inherited Alzheimer disease (DIAD) varies across individuals with Presenilin‐1 ( PS1) pathogenic mutations. Previous findings suggest that individuals with a PS1 mutation after codon 200 have more small vessel disease (SVD) pathology (Mann et al., 2001; Ryan et al., 2015). We investigated the effect of...

Background Both sporadic and dominantly inherited Alzheimer’s disease (DIAD) present with similar pathobiology and symptoms. A loss of proteostasis in AD has been identified with recent studies highlighting the role of ubiquitin‐dependent mechanisms in brain homeostasis and neurodegenerative diseases. The Ubiquitin Proteasome System (UPS) is respon...

Background Estimates of “brain‐predicted age” quantify apparent brain age compared to normative trajectories of neuroimaging features. Brain‐predicted age is elevated in sporadic Alzheimer disease (AD), but is underexplored in autosomal dominant AD (ADAD). We used a previously‐trained model (DeepBrainNet [DBN], Bashyam et al., 2020), which requires...

Background Population ageing will lead to a dramatic increase in dementia prevalence globally. Recent evidence suggest a decline in dementia incidence in High Income Countries due to increasing education levels and improvements in cardiovascular health. Although, most of the increase will occur in low and middle‐income countries (LMICs), there are...

Background Ethno‐racial differences are observed in amyloid (A), tau (T), and neurodegeneration (N) plasma biomarkers of Alzheimer’s disease (AD). In neuroimaging studies, structural and social determinant of health (SSDOH) factors and associated health outcomes may mediate observed racial differences in neurodegeneration markers. However, little i...

Background Alzheimer Disease (AD), the most common type of dementia, is accompanied by a generalized loss of neurons and cause severe changes in brain’s structure and function. Mild Cognitive Impairment is associated with a higher risk of developing dementia. This clinical classification is particularly relevant because each subtype is linked to a...

There are fundamental knowledge gaps about normal aging, cognitive decline, and the roles of Alzheimer’s Disease (AD) biomarkers in the Latino population. Previous studies report, ethno‐racial differences in amyloid (A), tau (T), and neurodegeneration (N) biomarkers and genetics of AD. However, most studies including Latino populations consider tho...

Background Clinical presentation of dominantly inherited Alzheimer disease (DIAD) varies across individuals with Presenilin‐1 (PS1) pathogenic mutations. Previous findings suggest that individuals with a PS1 mutation after codon 200 have more small vessel disease (SVD) pathology (Mann et al., 2001; Ryan et al., 2015). We investigated the effect of...

Background Estimates of “brain‐predicted age” quantify apparent brain age compared to normative trajectories of neuroimaging features. Brain‐predicted age is elevated in sporadic Alzheimer disease (AD), but is underexplored in autosomal dominant AD (ADAD). We used a previously‐trained model (DeepBrainNet [DBN], Bashyam et al., 2020), which requires...

Background “Brain-predicted age” estimates biological age from complex, nonlinear features in neuroimaging scans. The brain age gap (BAG) between predicted and chronological age is elevated in sporadic Alzheimer disease (AD), but is underexplored in autosomal dominant AD (ADAD), in which AD progression is highly predictable with minimal confounding...

Background Parkinson's disease (PD) is a rapidly growing neurodegenerative disorder, but up‐to‐date epidemiological data are lacking in Latin America. We sought to estimate the prevalence and incidence of PD and parkinsonism in Latin America. Methods We searched Medline, Embase, Scopus, Web of Science, Scientific Electronic Library Online, and Lit...

Background Little is known about the burden of parkinsonism and Parkinson’s disease (PD) in Latin America. Better understanding of health service use and clinical outcomes in PD is needed to improve its prognosis. Objective The aim of the study was to estimate the burden of parkinsonism and PD in six Latin American countries. Methods 12,865 parti...

Hub regions in the brain, recognized for their roles in ensuring efficient information transfer, are vulnerable to pathological alterations in neurodegenerative conditions, including Alzheimer Disease (AD). Given their essential role in neural communication, disruptions to these hubs have profound implications for overall brain network integrity an...

Approximately 5% of Alzheimer's disease cases have an early age at onset (<65 years), with 5-10% of these cases attributed to dominantly inherited mutations and the remainder considered as sporadic. The extent to which dominantly inherited and sporadic early onset Alzheimer’s disease overlap is unknown. In this study, we explored the clinical, cogn...

Background Despite the high burden of Alzheimer’s disease and other dementias among the Hispanic population worldwide, little is known about how dementia affects healthcare utilizations among this population outside of the US, in particular among those in the Caribbean region. Objective This study examines healthcare utilization associated with Al...

INTRODUCTION Studies suggest distinct differences in the development, presentation, progression, and response to treatment of Alzheimer's disease (AD) between females and males. We investigated sex differences in cognition, neuroimaging, and fluid biomarkers in dominantly inherited AD (DIAD). METHODS Three hundred twenty‐five mutation carriers (55...

Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation of the amyloid-β (Aβ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)—are hallmarks of the disease. However, other pathological brain processes are thought to be key disease m...

Background intrinsic capacity (IC) is a construct encompassing people’s physical and mental abilities. There is an implicit link amongst IC domains: cognition, locomotion, nutrition, sensory and psychological. However, little is known about the integration of the domains. Objectives to investigate patterns in the presentation and evolution of IC d...

Background: Neuropsychiatric symptoms (NPSs) are common in neurodegenerative diseases; however, little is known about the prevalence of NPSs in Hispanic populations. Methods: Using data from community-dwelling participants age 65 years and older enrolled in the 10/66 study (N = 11,768), we aimed to estimate the prevalence of NPSs in Hispanic pop...

Background: The burden of Alzheimer’s disease and related dementia (ADRD) is projected to disproportionally impact low-middle-income countries (LMICs). However, there is a systematic under-representation of LMICs in ADRD clinical trial platforms. Methods: We aimed to determine the global distribution of ADRD clinical trials and identify existing b...

Latin America and the Caribbean (LAC) countries are experiencing unprecedentedly rapid demographic ageing. Growing evidence shows that cardiovascular health (CVH) is associated with brain health. Little is known about this topic among older adults in Latin America, where the number of people living with dementia is rising. The present study aimed t...

More than 300 variants in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) genes have been reported to cause Dominantly Inherited Alzheimer Disease (DIAD). However, most of these reports come from non‐Hispanic whites and the full extent of DIAD remains understudied in Latin American (LatAm) countries. Here we descr...

Pre‐symptomatic genetic testing for individuals with dominantly inherited Alzheimer’s disease (DIAD) is now attracting interest due to the existence of therapeutic trials available to this population. Although the impact and the main drivers influencing the decision to seek genetic testing have been widely studied in High‐Income Countries, these re...

Although Alzheimer disease (AD) related changes of tau can be measured in fluids and by positron emission tomography (PET), it remains unclear how these two are associated across the AD spectrum. To further explore the association between soluble tau related biomarkers‐ cerebrospinal fluid (CSF) total tau and p‐tau181‐ and neurofibrillary tangles (...

Prevention of Alzheimer’s dementia may encompass both avoiding the AD pathological processes (resistance) and coping with AD pathology (resilience). Increasing evidence implicates resistance/resilience factors (e.g., level of education, socio‐economic status [SES], physical activity [PA]) occurring through life as potential modifiers of age at symp...

Researchers working on studies of dementia in Latin American and Caribbean (LAC) countries encounter numerous challenges, in particular, access to financial resources due to limited funding and operational barriers which limit the possibility of recruiting a diverse cohort from the LAC. Addressing challenges to access research is important to ensur...

In the absence of clinically meaningful disease‐modifying treatments, the number of adults with dementia worldwide is projected to more than triple. Much of this increase will occur in low and middle‐income countries (LMICs); by 2050, 68% of adults living with dementia will be in LMICs. However, there is a gross under‐representation of LMICs in his...

Objective: To determine the characteristics of participants with amyloid-related imaging abnormalities (ARIA) in a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease (DIAD). Methods: 142 DIAD mutation carriers received either gantenerumab SC (n=52), solanezumab IV (n=50), or placebo (n=40). Participants underwent asse...

Background In fewer than 1% of patients, AD is caused by autosomal dominant mutations in either the presenilin 1 ( PSEN1 ), presenilin 2 ( PSEN2 ), or amyloid precursor protein ( APP ) genes. The full extent of familial AD and frequency of these variants remains understudied in Latin American (LatAm) countries. Due to the rare nature of these varia...

Between 2018 and 2019, multiple clinical trials ended earlier than planned, resulting in calls to improve communication with and support for participants and their study partners (“dyads”). The multidisciplinary Participant Follow‐Up Improvement in Research Studies and Trials (Participant FIRST) Work Group met throughout 2021. Its goals were to ide...

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most commonly diagnosed human prion disease caused by the abnormal misfolding of the 'cellular' prion protein (PrPC) into the transmissible 'scrapie-type' prion form (PrPSc). Neuropathologic evaluation of brains with sCJD reveals abnormal PrPSc deposits in grey matter structures, often associated wit...

Introduction: Apolipoprotein E (APOE) is considered the major susceptibility gene for developing Alzheimer's disease. However, the strength of this risk factor is not well established across diverse Hispanic populations. Methods: We investigated the associations among APOE genotype, dementia prevalence, and memory performance (immediate and dela...

Background Because of high prevalence of Alzheimer’s disease (AD) in low- and middle-income countries (LMICs), there is an urgent need for inexpensive and minimally invasive diagnostic tests to detect biomarkers in the earliest and asymptomatic stages of the disease. Blood-based biomarkers are predicted to have the most impact for use as a screenin...

Background: Age and gender specific prevalence rates for parkinsonism and Parkinson's disease (PD) are important to guide research, clinical practice, and public health planning; however, prevalence estimates in Latin America (LatAm) are limited. We aimed to estimate the prevalence of parkinsonism and PD and examine related risk factors in a cohor...

The Alzheimer's Association hosted the second Latinos & Alzheimer's Symposium in May 2021. Due to the COVID‐19 pandemic, the meeting was held online over 2 days, with virtual presentations, discussions, mentoring sessions, and posters. The Latino population in the United States is projected to have the steepest increase in Alzheimer's disease (AD)...

Background Rapid technological advances offer a possibility to develop cost‐effective digital cognitive assessment tools. However, it is unclear whether these measures are suitable for application in populations from Low and Middle‐Income Countries (LMIC). Methods In this cross‐sectional study, we examined the accuracy and validity of the Brian He...

Background Previous research showed that up to 56% of all dementia cases in Latin America could potentially be prevented if all modifiable risk factors were eliminated. Trends of studies in Latin America show, however, that lifestyles are declining. In absence of a cure, prevention is crucial. The aim was to develop a tool that can be used in prima...

Background In addition to anti‐Aβ immunization therapeutics completing phase II/III clinical trials ¹ , drugs targeting tau, inflammation, and apolipoprotein E, are in clinical development. Due to its close association with cognitive and clinical impairment, tau is one of the most promising targets currently ready for phase II trials. In this study...

Background Tau pathology is closely associated with the onset and progression of Alzheimer’s disease. Recent advances in drugs that target tau suggest the potential to prevent or attenuate the pathophysiology and pathology of tau. Novel CSF and blood tau species including specific phospho‐tau (p‐tau) and truncated species containing the microtubule...

Background Amyloid‐related imaging abnormalities (ARIA), edema (E) or hemorrhagic (H) type, have been reported in trials of anti‐β‐amyloid passive immunotherapies in sporadic and dominantly inherited Alzheimer Disease (DIAD). However, beyond APOE‐ɛ4 the risk factors and clinical implications of ARIA are not well understood, especially in DIAD popul...

Background Approximately 5% of Alzheimer disease (AD) occurs before the age of 65, known as early onset AD (EOAD); 5‐10% of the patients with EOAD are caused by dominantly inherited mutations (DIAD) and the remainder appear to be sporadic EOAD (sEOAD). The extent to which clinical presentations, cognitive and biomarker profiles in DIAD and sEOAD ov...

Background Alzheimer’s disease (AD) is a neurodegenerative disease that is characterized by extracellular amyloid plaques, intracellular neurofibrillary tangles, and progressive cognitive decline. More than 200 mutations in APP , PSEN1 , and PSEN2 cause autosomal dominant AD (ADAD). However, common and rare variants also exist within these genes th...

Background: A small proportion of Alzheimer disease (AD), known as early onset AD (EOAD), has symptomatic age at onset (AAO) before age 65. About 5-10% of EOAD is dominantly inherited (DIAD); the rest is termed to be sporadic (sEOAD). Although DIAD and sEOAD share the hallmark plaques and tangles that define AD neuropathologic change (ADNC), the r...

Background Approximately 5% of patients with Alzheimer’s Disease (AD) develop symptoms before age 65, with this early‐onset presentation attributed to either sporadic (sEOAD) or dominantly‐inherited (DIAD) etiology. Both sEOAD and DIAD are characterized by brain amyloid‐beta (Aβ) accumulation and neurodegeneration, but differences in topography and...

Background: Latinos represent the fastest growing proportion of dementia cases among different ethnic groups. Most of the studies in Alzheimer's Disease (AD) include Latino populations within the same group, failing to sufficiently account for the real richness of linguistic, ethnic, ancestry, cultural, and socioeconomic diversity represented acro...

Background: APOE-ε4 allele is the most significant genetic risk factor for late-onset Alzheimer disease (AD). The magnitude of the association between the APOE-ε4 allele, AD, and cognitive decline has been shown to be stronger in populations of European descent relative to populations of African descent. However, these associations have been under...

Alzheimer’s disease (AD) and dementia has emerged as a significant societal issue and a global priority. The prevalence of dementia is rising more rapidly in low and middle income countries (LMIC) than in high income countries. A growing body of evidence shows that prevention through risk factor management is the key to reducing the burden of demen...

Background The World Health Organization (WHO) has reframed health and healthcare for older people around achieving the goal of healthy ageing. The recent WHO Integrated Care for Older People (ICOPE) guidelines focus on maintaining intrinsic capacity, i.e., addressing declines in neuromusculoskeletal, vitality, sensory, cognitive, psychological, an...

Introduction: The historical development, frequency, and impact of frontotemporal dementia (FTD) are less clear in Latin America than in high-income countries. Although there is a growing number of dementia studies in Latin America, little is known collectively about FTD prevalence studies by country, clinical heterogeneity, risk factors, and genet...

Introduction: Despite high dementia prevalence in Hispanic populations globally, especially Caribbean Hispanics, no study has comparatively examined the association between education and dementia among Hispanics living in the Caribbean Islands and older adults in the United States. Methods: We used data on 6107 respondents aged 65 and older in t...

Alzheimer disease (AD) prevention trials hold the promise to delay or prevent cognitive decline and dementia onset by intervening before significant neuronal damage occurs. In recent years, the first AD prevention trials have launched and are yielding important findings on the biology of targeting asymptomatic AD pathology. However, there are limit...