Lawrence Honig

• Professor
• Columbia University

Objective Early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) differ in many respects. Here, we address the issue of possible differences in fibrillar amyloid pathology as measured by positron emission tomography (PET), which remains unresolved due to the lack of large‐scale comparative studies. Methods Three hundred n...

Amyloid‐β (Aβ) positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) biomarkers are now established tools in the diagnostic workup of patients with Alzheimer's disease (AD), and their use is anticipated to increase with the introduction of new disease‐modifying therapies. Although these biomarkers are comparable alternatives in r...

We investigated genetic regulators of circulating plasma metabolites to identify pathways underlying biochemical changes in clinical and biomarker-assisted diagnosis of Alzheimer's disease (AD). We computed metabolite quantitative trait loci by using whole genome sequencing and small molecule plasma metabolites from 229 older adults with clinical A...

INTRODUCTION Early‐onset and late‐onset Alzheimer's disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head‐to‐head comparison of cortical atrophy in EOAD and LOAD, using two large and well‐characterized co...

Brain network dynamics have been extensively explored in patients with subjective cognitive decline (SCD). However, these studies are susceptible to individual differences, scanning parameters, and other confounding factors. Therefore, how to reveal subtle SCD-related subtle changes remains unclear. Cross-sectional and longitudinal resting-state fu...

Background Plasma biomarkers for Alzheimer’s disease (AD) are indicators of neuropathological changes. Biomarker cutoffs may not consistently indicate the presence or absence of a pathology. Discrepant biomarker levels are observed in some cognitively normal subjects and patients with clinically diagnosed AD, with some asymptomatic individuals havi...

For Alzheimer’s disease (AD), there are currently two FDA‐approved agents developed as disease‐modifying treatments. Approval of lecanemab (Leqembi®) in 2023, via accelerated approval mechanism, followed by traditional approval accompanied by medical coverage decision by the Center for Medicare Services, has resulted in increasing use of this anti‐...

Background Multi‐omics integration can clarify molecular mechanisms contributing to Alzheimer’s Disease (AD). We conducted a quantitative trait locus (QTL) analysis across three omics layers to identify genetic variants that regulate metabolomics, gene expression, and DNA methylation in AD. Method We analyzed data from Caribbean Hispanic individua...

Background We investigated the relationship between the cerebrospinal fluid (CSF) proteome in Alzheimer’s disease (AD) and the clinical and biomarker‐assisted diagnoses. Methods CSF was collected in 500 individuals of non‐Hispanic white, African Americans, and Caribbean Hispanic individuals from Dominican Republic and New York City. CSF biomarkers...

Background Plasma biomarkers may be utilized to assist in diagnosis of Alzheimer's disease. However, in a cohort of Caribbean Hispanic individuals we have shown that there are both individuals who are biomarker positive but without dementia, and biomarker negative but diagnosed with dementia. Here we examine education and neuropsychological testing...

Background There has been a great advancement in clinical application of blood‐based biomarkers of Alzheimer’s Disease (AD) over the past years. We aimed to examine whether cardiovascular comorbidities may contribute to clinical cognitive impairment in individuals with low level of these biomarkers. Method The current cross‐sectional study include...

Background Blood‐based Alzheimer's disease (AD) biomarkers have been increasingly employed for diagnostic and prognostic purposes, thanks to high diagnostic accuracy in distinguishing AD from healthy controls or other dementia types. p‐tau217 exhibits stronger associations with AD hallmarks in CSF and brain, compared to other p‐tau isoforms. Furthe...

Background Recent advances in diagnostics have made it possible to identify early signs of the pathophysiological changes underlying Alzheimer’s Disease (AD) via blood tests. However, the use of blood‐based biomarkers (BBBMs) for the early detection of AD may be limited in primary care settings despite its potential for wide access and early detect...

Background The earliest recognized biomarker of AD is deposition of Aβ amyloid that leads to formation of plaques and may, over time, trigger or at least be followed by gliosis/neuroinflammation and neurofibrillary tangles, accompanied by neurodegenerative changes including neuronal and synaptic loss. We have previously reported that semaphorin 4D...

Background Blood‐based biomarkers may aid in the diagnosis of Alzheimer’s Disease (AD), but their contribution may be confounded by the presence of multiple chronic conditions and have not been well‐tested in community populations. In the current study, we aimed to determine whether blood‐based biomarkers can aid in refining a multi‐ethnic, urban c...

Background Blood-based Alzheimer’s disease (AD) biomarkers have been increasingly employed for diagnostic, prognostic, and therapeutic monitoring purposes, due to accuracy in distinguishing AD pathophysiologic process. Compared to other p-tau isoforms, plasma p-tau217 exhibits stronger associations with AD hallmarks in CSF and brain. However, most...

Background: Soluble species of multimeric amyloid-beta including globular amyloid-beta oligomers (AβOs) and linear amyloid-beta protofibrils are toxic to neurons. Sabirnetug (ACU193) is a humanized monoclonal antibody, raised against globular species of soluble AβO, that has over 650-fold greater binding affinity for AβOs over monomers and appears...

Genetic risk factors for late-onset Alzheimer’s disease (LOAD) have been extensively studied in the general population of European background. Indeed, significant genetic variants with low to moderate contributions to LOAD have been used to calculate Polygenic Risk Scores (PRS) to identify individuals with a higher genetic risk of LOAD. The Long Li...

Clinical studies have consistently shown that various classes of lipids are involved in the early stages of Alzheimer’s Disease (AD). To better understand the biological processes involved, we examined three layers of omic data from the Long Life Family Study (LLFS), which aimed to investigate the biological basis of familial exceptional longevity....

INTRODUCTION Early‐onset Alzheimer's disease (EOAD) manifests prior to the age of 65, and affects 4%–8% of patients with Alzheimer's disease (AD). The current analyses sought to examine longitudinal cognitive trajectories of participants with early‐onset dementia. METHODS Data from 307 cognitively normal (CN) volunteer participants and those with...

INTRODUCTION Early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) share similar amyloid etiology, but evidence from smaller‐scale studies suggests that they manifest differently clinically. Current analyses sought to contrast the cognitive profiles of EOAD and LOAD. METHODS Z‐score cognitive‐domain composites for 311 am...

INTRODUCTION Psychotropic medication (PM) use in behavioral‐variant frontotemporal dementia (bvFTD) is higher than in other dementias. However, no information exists on whether PM use differs between sporadic and genetic bvFTD. METHODS We analyzed data from sporadic and genetic bvFTD participants with PM prescriptions in the Advancing Research and...

The availability of anti-amyloid therapy for mild cognitive impairment (MCI) due to Alzheimer’s disease and mild Alzheimer’s dementia (AD) has underscored the need for realistic estimates of the population with AD/MCI within the healthcare system to assure adequate preparedness. We hypothesize that administrative databases can provide real-world ep...

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...

Introduction: Polygenic risk score (PRS) is effective in predicting AD risk among Europeans but remains understudied in Hispanics. Diverse genome-wide association studies (GWAS) data across multiple ancestries may improve PRS predictions. We evaluated PRS performance to predict AD disease risk using novel methods in the largest available African, E...

Background and objectives: TMEM106B has been proposed as a modifier of disease risk in FTLD-TDP, particularly in GRN pathogenic variant carriers. Furthermore, TMEM106B has been investigated as a disease modifier in the context of healthy aging and across multiple neurodegenerative diseases. The objective of this study was to evaluate and compare t...

By age 40 years, over 90% of adults with Down syndrome have Alzheimer’s disease pathology and most progress to dementia. Despite having few systemic vascular risk factors, individuals with Down syndrome have elevated cerebrovascular disease markers that track with the clinical progression of Alzheimer’s disease, suggesting a role of cerebrovascular...

Background Plasma neurofilament light chain (NfL) is a blood biomarker of neurodegeneration, including Alzheimer’s disease. However, its usefulness may be influenced by common conditions in older adults, including amyloid-β (Aβ) deposition and cardiometabolic risk factors like hypertension, diabetes mellitus (DM), impaired kidney function, and obes...

INTRODUCTION Cardiovascular health is important for brain aging, yet its role in the clinical manifestation of autosomal dominant or atypical forms of dementia has not been fully elucidated. We examined relationships between Life's Simple 7 (LS7) and clinical trajectories in individuals with autosomal dominant frontotemporal lobar degeneration (FTL...

INTRODUCTION Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early Alzheimer's disease (AD) pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify cerebrospinal fluid (CSF) biomarkers for AD‐related central...

Purpose of Review The most common four neurodegenerative atypical parkinsonian disorders (APDs) are progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal syndrome (CBS), and dementia with Lewy bodies (DLB). Their formal diagnostic criteria often require subspecialty experience to implement as designed and all require exc...

Background: This study compared the mortality risk of long-lived siblings with the U.S. population average and their spouse controls, and investigated the leading causes of death and the familial effect in death pattern. Methods: In the Long Life Family Study (LLFS), 1,264 proband siblings (Mean age 90.1, SD 6.4) and 172 spouses (83.8, 7.2) from...

Background: Focused ultrasound (FUS) in combination with microbubbles has recently shown great promise in facilitating blood-brain barrier (BBB) opening for drug delivery and immunotherapy in Alzheimer's disease (AD). However, it is currently limited to systems integrated within the MRI suites or requiring post-surgical implants, thus restricting i...

Background and objectives: The clinical diagnosis of dementia with Lewy bodies (DLB) depends on identifying significant cognitive decline accompanied by core features of parkinsonism, visual hallucinations, cognitive fluctuations, and REM sleep behavior disorder (RBD). Hyposmia is one of the several supportive features. α-Synuclein seeding amplifi...

Background Amyloid beta protein (Aβ) is a treatment target in Alzheimer’s Disease (AD). Lowering production of its parent protein, APP, has benefits in preclinical models. Posiphen, an orally administered small molecule, binds to an iron-responsive element in APP mRNA and decreases translation of APP and Aβ. To augment human data for Posiphen, we e...

Background Frontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged <65 years. Several challenges to conducting in-person evaluations in FTLD illustrate an urgent need to develop remote, accessible, and low-burden assessment techniques. Studies of unobtrusive monitoring of at-home computer use in older adults with...

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 cases and...

INTRODUCTION: Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early AD pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify CSF biomarkers for AD-related CNS pathophysiologic changes using tissue and flui...

Cerebrovascular and α-synuclein pathologies are frequently observed alongside Alzheimer disease (AD). The heterogeneity of AD necessitates comprehensive approaches to postmortem studies, including the representation of historically underrepresented ethnic groups. In this cohort study, we evaluated small vessel disease pathologies and α-synuclein de...

Background Alzheimer disease (AD) is a major health problem of aging, with tremendous burden on healthcare systems, patients, and families globally. Lecanemab, an FDA-approved amyloid beta (Aβ)-directed antibody indicated for the treatment of early AD, binds with high affinity to soluble Aβ protofibrils, which have been shown to be more toxic to ne...

Background and Objectives: TMEM106B has been proposed as a modifier of disease risk in FTLD-TDP, particularly in GRN mutation carriers. Furthermore, TMEM106B has been investigated as a disease modifier in the context of healthy aging and across multiple neurodegenerative diseases. The objective of this study is to evaluate and compare the effect of...

Alzheimer's disease (AD) is a neurodegenerative disease that commonly causes dementia. Identifying biomarkers for the early detection of AD is an emerging need, as brain dysfunction begins two decades before the onset of clinical symptoms. To this end, we reanalyzed untargeted metabolomic mass spectrometry data from 905 patients enrolled in the AD...

The pathophysiological mechanisms driving disease progression of frontotemporal lobar degeneration (FTLD) and corresponding biomarkers are not fully understood. We leveraged aptamer-based proteomics (> 4,000 proteins) to identify dysregulated communities of co-expressed cerebrospinal fluid proteins in 116 adults carrying autosomal dominant FTLD mut...

Background: Amyloid beta protein (A-beta) is a treatment target in Alzheimer Disease (AD). Lowering production of its parent protein, APP, has benefits in preclinical models. Posiphen binds to an iron-responsive element in APP mRNA and decreases translation of APP and Aβ. To augment human data for Posiphen, we evaluated safety, tolerability and pha...

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...

Background Polygenic effects have been proposed to account for some disease phenotypes; these effects are calculated as a polygenic risk score (PRS). This score is correlated with Alzheimer’s disease (AD)-related phenotypes, such as biomarker abnormalities and brain atrophy, and is associated with conversion from mild cognitive impairment (MCI) to...

INTRODUCTION Increasing evidence suggests that amyloid reduction could serve as a plausible surrogate endpoint for clinical and cognitive efficacy. The double‐blind phase 3 DIAN‐TU‐001 trial tested clinical and cognitive declines with increasing doses of solanezumab or gantenerumab. METHODS We used latent class (LC) analysis on data from the Domin...

BACKGROUND Alzheimer's disease (AD) biomarkers can help differentiate cognitively unimpaired (CU) individuals from mild cognitive impairment (MCI) and dementia. The role of AD biomarkers in predicting cognitive impairment and AD needs examination. METHODS In 628 CU individuals from a multi‐ethnic cohort, amyloid beta (Aβ)42, Aβ40, phosphorylated t...

Background Genetic Studies of Alzheimer’s Disease in Caribbean Hispanics (CH) has been ongoing for over 20 years. Our primary goal was to identify genes in large well‐phenotyped, multiplex families, and sporadic cases and controls. This longitudinal collection of data represents a unique resource for the scientific community. The project is led by...

Background Genetic Studies of Alzheimer’s Disease in Caribbean Hispanics (CH) has been ongoing for over 20 years. Our primary goal was to identify genes in large well‐phenotyped, multiplex families, and sporadic cases and controls. This longitudinal collection of data represents a unique resource for the scientific community. The project is led by...

Background Neuropathological hallmarks of AD, amyloid plaques and neurofibrillary tangles, have been described in dementia with Lewy bodies (DLB). Less is known about changes in pre‐mortem cerebrospinal fluid (CSF) amyloid and tau biomarker status in DLB. CSF biomarkers for amyloid (A), tau (T), and neurodegeneration (N) can be utilized to define p...

Background Posiphen has been reported to decrease translation of beta amyloid precursor protein (APP) mRNA, resulting in decreased production of Aβ. ¹ The pharmacodynamics of Posiphen require further clarification to better assess its therapeutic potential. Method The DISCOVER phase 1b placebo controlled RCT enrolled patients with MCI or mild AD d...

Background Energy, amino acid, and lipid metabolism are dysregulated in Alzheimer’s Disease. We investigated circulating plasma metabolites to capture systemic biochemical changes associated with Alzheimer’s disease (AD) using the clinical diagnosis and followed by the addition of plasma‐based biomarkers. Method Exogenous and endogenous metabolite...

In order to provide a comprehensive evaluation of the non‐genetic factors involved in the development of Alzheimer’s disease and related disorders it is necessary to develop a systematic process to capture the range of environmental and social influences. Exposomics has emerged as an approach to do this. Using high‐resolution mass spectrometry and...

Background Blood‐based biomarkers have the unique potential to make diagnoses along the Alzheimer’s Disease (AD) continuum. The value of these plasma‐based biomarkers in AD among different race and ethnicity, sex, and genetic status groups needs to be evaluated. Method The study included 603 participants of the Washington Heights Inwood Columbia A...

Background The utility of plasma‐based Alzheimer’s biomarkers in differentiating cognitively healthy individuals from those with Mild Cognitive Impairment (MCI) or Alzheimer’s disease (AD) has been widely investigated in cross‐sectional studies. There are fewer data on longitudinal change of these biomarkers over time, particularly in multi‐ethnic...

Background We examined neuropsychiatric symptoms (NPS) and psychotropic medication use at the midway point of data collection of the Longitudinal Early‐onset Alzheimer’s Disease Study (LEADS). We compared amyloid‐positive early‐onset Alzheimer’s disease (EOAD) participants and amyloid‐negative early‐onset non‐Alzheimer’s disease [EOnonAD]) particip...

Background Approximately 10‐25% of amnestic early‐onset dementia are negative for amyloid (Early‐onset non‐Alzheimer’s Disease, EOnonAD). EOnonAD is a heterogenous group with various etiologies. In order to better understand the traits of EOnonAD, we clustered amnestic EOnonAD individuals according to cognitive patterns. Method Cognitive data of 6...

Background Dementia with Lewy Bodies (DLB) is defined by abnormal deposits of alpha‐synuclein (Lewy bodies), in the brain. DLB may be accompanied by variable co‐pathology, especially Alzheimer’s Disease (AD). DLB is diagnosed clinically, with definitive diagnosis only possible at autopsy. Misdiagnosis may occur due to overlapping symptoms in differ...

Background Intake of key nutrients is associated with improved cognitive performance and reduced risk of Alzheimer’s dementia (AD). We examined whether omega‐3 polyunsaturated fatty acid (O‐3 PUFA), omega‐6 (O‐6) PUFA, and monounsaturated fat (MUFA) from foods are associated with plasma biomarkers for AD. Method We selected 695 participants in a c...

Background Hippocampal and amygdala subfields variably affect cognitive impairment in neurodegenerative diseases. Subfields of these regions can be well segmented using modern neuroimaging tools but their role in neurodegenerative disease is under active investigation. In this study, we identified hippocampal and amygdala subregions predictive of c...

Background Genetic risk factors have been explored extensively for late onset Alzheimer’s Disease (LOAD). The largest meta‐analysis GWAS studies to date (Bellenguez et al., 2022) identified 83 single nucleotide polymorphisms (SNPs) associated with LOAD in the general population. The Long Life Family Study (LLFS) is aimed to identify factors associa...

Background Focused ultrasound (FUS) in combination with microbubbles has recently shown great promise in facilitating blood-brain barrier (BBB) opening for drug delivery and immunotherapy in Alzheimer’s disease (AD). However, it is currently limited to systems integrated within the MRI suites or requiring post-surgical implants, thus restricting it...

INTRODUCTION Magnetic resonance imaging (MRI) research has advanced our understanding of neurodegeneration in sporadic early‐onset Alzheimer's disease (EOAD) but studies include small samples, mostly amnestic EOAD, and have not focused on developing an MRI biomarker. METHODS We analyzed MRI scans to define the sporadic EOAD‐signature atrophy in a...

Introduction: One goal of the Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is to investigate the genetic etiology of early onset (40-64 years) cognitive impairment. Toward this goal, LEADS participants are screened for known pathogenic variants. Methods: LEADS amyloid-positive early-onset Alzheimer's disease (EOAD) or negative earl...

Background: Comorbidities may influence the levels of blood-based biomarkers for Alzheimer’s disease (AD). We investigated whether differences in risk factors or comorbid conditions might explain the discordance between clinical diagnosis and biomarker classifications in a multi-ethnic cohort of elderly individuals. Aims: To evaluate the relationsh...

INTRODUCTION The National Institute on Aging – Alzheimer's Association (NIA‐AA) ATN research framework proposes to use biomarkers for amyloid (A), tau (T), and neurodegeneration (N) to stage individuals with AD pathological features and track changes longitudinally. The overall aim was to utilize this framework to characterize pre‐mortem ATN status...

BACKGROUND Frontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged <65 years. Several challenges to conducting in-person evaluations in FTLD illustrate an urgent need to develop remote, accessible, and low-burden assessment techniques. Studies of unobtrusive monitoring of at-home computer use in older adults with...

Background We profiled circulating plasma metabolites to identify systemic biochemical changes in clinical and biomarker-assisted diagnosis of Alzheimer’s disease (AD). Methods We used an untargeted approach with liquid chromatography coupled to high-resolution mass spectrometry to measure small molecule plasma metabolites from 150 clinically diagn...

Introduction: We aimed to describe baseline amyloid-beta (Aβ) and tau-positron emission tomograrphy (PET) from Longitudinal Early-onset Alzheimer's Disease Study (LEADS), a prospective multi-site observational study of sporadic early-onset Alzheimer's disease (EOAD). Methods: We analyzed baseline [18F]Florbetaben (Aβ) and [18F]Flortaucipir (tau)...

Introduction: The Rey Auditory Verbal Learning Test (RAVLT) is a useful neuropsychological test for describing episodic memory impairment in dementia. However, there is limited research on its utility in early-onset Alzheimer's disease (EOAD). We assess the influence of amyloid and diagnostic syndrome on several memory scores in EOAD. Methods: W...

Background: We investigated systemic biochemical changes in Alzheimer's disease (AD) by investigating the relationship between circulating plasma metabolites and both clinical and biomarker-assisted diagnosis of AD. Methods: We used an untargeted approach with liquid chromatography coupled to high-resolution mass spectrometry to measure exogenous a...

INTRODUCTION: Alzheimer's disease (AD) biomarkers can help differentiate cognitively unimpaired (CU) individuals from mild cognitive impairment (MCI) and dementia. The role of AD biomarkers in predicting cognitive impairment and AD needs examination. METHODS: In 628 CU individuals from a multi-ethnic cohort, Aβ42, Aβ40, phosphorylated tau-181 (P-ta...

Cerebrovascular injury frequently occurs in children with sickle cell anaemia (SCA). Limited access to magnetic resonance imaging and angiography (MRI‐MRA) in sub‐Saharan Africa impedes detection of clinically unapparent cerebrovascular injury. Blood‐based brain biomarkers of cerebral infarcts have been identified in non‐SCA adults. Using plasma sa...

Introduction: We used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early-onset Alzheimer's disease (EOAD). Methods: We included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non-Alzheimer's disease (EOnonAD) participants from the Longitudinal Early-Onset Alzheimer's Disease Study...

Introduction: We compared white matter hyperintensities (WMHs) in early-onset Alzheimer's disease (EOAD) with cognitively normal (CN) and early-onset amyloid-negative cognitively impaired (EOnonAD) groups in the Longitudinal Early-Onset Alzheimer's Disease Study. Methods: We investigated the role of increased WMH in cognition and amyloid and tau...

Introduction: One goal of the Longitudinal Early Onset Alzheimer's Disease Study (LEADS) is to define the fluid biomarker characteristics of early-onset Alzheimer's disease (EOAD). Methods: Cerebrospinal fluid (CSF) concentrations of Aβ1-40, Aβ1-42, total tau (tTau), pTau181, VILIP-1, SNAP-25, neurogranin (Ng), neurofilament light chain (NfL), a...

Rationale: Bilateral sonication with focused ultrasound (FUS) in conjunction with microbubbles has been shown to separately reduce amyloid plaques and hyperphosphorylated tau protein in the hippocampal formation and the entorhinal cortex in different mouse models of Alzheimer's disease (AD) without any therapeutic agents. However, the two pathologi...

Despite the increasing demographic diversity of the United States’ aging population, there remain significant gaps in post-mortem research investigating the ethnoracial heterogeneity in the neuropathological landscape of Alzheimer Disease (AD). Most autopsy-based studies have focused on cohorts of non-Hispanic White decedents (NHWD), with few studi...

Introduction: We examined neuropsychiatric symptoms (NPS) and psychotropic medication use in a large sample of individuals with early-onset Alzheimer's disease (EOAD; onset 40-64 years) at the midway point of data collection for the Longitudinal Early-onset Alzheimer's Disease Study (LEADS). Methods: Baseline NPS (Neuropsychiatric Inventory - Qu...

Objective: The Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) seeks to provide comprehensive understanding of early-onset Alzheimer's disease (EOAD; onset <65 years), with the current study profiling baseline clinical, cognitive, biomarker, and genetic characteristics of the cohort nearing the data-collection mid-point. Methods: Data...

Purpose Pittsburgh Compound-B (¹¹C-PiB) and ¹⁸F-florbetapir are amyloid-β (Aβ) positron emission tomography (PET) radiotracers that have been used as endpoints in Alzheimer’s disease (AD) clinical trials to evaluate the efficacy of anti-Aβ monoclonal antibodies. However, comparing drug effects between and within trials may become complicated if dif...

Importance: Cerebrospinal fluid (CSF) and plasma biomarkers can detect biological evidence of Alzheimer disease (AD), but their use in low-resource environments and among minority ethnic groups is limited. Objective: To assess validated plasma biomarkers for AD among adults of Caribbean Hispanic ethnicity. Design, setting, and participants: In...

Introduction: Lecanemab is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that preferentially targets soluble aggregated Aβ species (protofibrils) with activity at amyloid plaques. Amyloid-related imaging abnormalities (ARIA) profiles appear to differ for various anti-amyloid antibodies. Here, we present ARIA data from a large phase 2 le...

Previously, we found that female sex is associated with greater pathology burden in early‐onset Alzheimer’s disease (EOAD) in the Longitudinal EOAD Study (LEADS). Here, we have expanded our analyses by adding APOE‐ε4 carrier status as a further predictor of EOAD pathologic burden. We included 180 EOAD LEADS participants with available APOE genotype...

Anti‐amyloid antibodies administered to patients with Alzheimer’s disease can result in marked reduction of brain amyloid as measured by neuroimaging with amyloid PET ligands. However, there is a lack of pathological data. Here we present neuropathological findings in a patient who received ∼173 weeks of (interrupted) treatment with lecanemab (BAN2...

18F‐Florbetaben (FBB) is a PET radioligand approved for determining binary amyloid status. According to the product label, FBB images may be acquired anytime 45‐130 minutes post injection. Protocols vary in the acquisition of FBB with respect to use of Early (50‐70 minutes‐post‐injection) or Late (90‐110 minutes‐post‐injection) frames. Identifying...

18F‐Florbetaben (FBB) is a PET radioligand approved for determining binary amyloid status. According to the product label, FBB images may be acquired anytime 45‐130 minutes post injection. Protocols vary in the acquisition of FBB with respect to use of Early (50‐70 minutes‐post‐injection) or Late (90‐110 minutes‐post‐injection) frames. Identifying...

Background: Genome-wide Association Studies (GWAS) have reshaped our understanding of the genetic bases of complex diseases in general and neurodegenerative diseases in particular. Despite being a common disorder, dementia with Lewy bodies (DLB), which, together with Parkinson's disease dementia (PDD), comprise the umbrella term Lewy body dementias...