James B Leverenz

• MD
• Director Center for Brain Health at Cleveland Clinic

INTRODUCTION Human herpesvirus (HHV) has been linked to Alzheimer's disease (AD), but the underlying mechanisms remain unknown. METHODS We leveraged functional genomics data from Religious Orders Study or the Rush Memory and Aging Project (ROS/MAP) and Mount Sinai Brain Bank (MSBB) brain biobanks and single‐cell RNA‐sequencing data from HHV‐infect...

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder. However, current treatments only manage symptoms and lack the ability to slow or prevent disease progression. We utilized a systems genetics approach to identify potential risk genes and repurposable drugs for PD. First, we leveraged non-coding genome-wide association...

Lewy body dementia (LBD) clinically is characerized by a complex myriad of cognitive, behavioral, motor, sleep and autonomic symptoms that can be challenging to manage, particularly in the context of the fluctuations that are so characteristic for these patients. The DIAMOND Lewy Toolkits offer a resource to support clinicians in recognizing and ma...

Background Although investment in biomedical and pharmaceutical research has increased significantly over the past two decades, there are no oral disease‐modifying treatments for Alzheimer’s disease (AD). Method We performed comprehensive human genetic and multi‐omics data analyses to test likely causal relationship between EPHX2 (encoding soluble...

Background This study set to determine if 123I‐ioflupane SPECT striatal binding ratio (SBR) correlated with parkinsonian symptoms measured on Movement Disorder Society – Unified Parkinson’s Disease Rating Scale Part III (UPDRS‐III) in a dementia with Lewy bodies (DLB) cohort and if SBR measured at baseline could predict progression of parkinsonian...

Background Synuclein Aggregate Assays (SAA) in cerebrospinal fluid (CSF) and in skin biopsy have been shown to successfully identify underlying synuclein (Lewy body) pathology in patients with Parkinson's disease. Data in Lewy Body Dementia (LBD) is limited, particularly with pathologic confirmation and staging of underlying Lewy body pathology, an...

Background Inflammatory changes are a key element of Alzheimer’s disease (AD)pathophysiology. However, there is lack of clarity regarding key gene drivers of the cytokines identified as playing a role in clinical AD progression and their relationship to AD biomarkers to understand their clinical role. Method We investigated transcriptomic datasets...

Background This study set to determine if 123I‐ioflupane SPECT striatal binding ratio (SBR) correlated with parkinsonian symptoms measured on Movement Disorder Society – Unified Parkinson’s Disease Rating Scale Part III (UPDRS‐III) in a dementia with Lewy bodies (DLB) cohort and if SBR measured at baseline could predict progression of parkinsonian...

Background Alzheimer’s disease (AD) is a pathologically heterogeneous disease making it a challenge to develop effective treatments. Emerging evidence suggests that there are pathological differences between women and men with AD. More biomarkers are needed to enhance sex‐specific precision medicine in AD. Cerebrospinal fluid (CSF) biomarkers for a...

Background International collaboration is crucial to the future of research in dementia with Lewy bodies (DLB). Although it is hoped that a single global DLB cohort can be created through combination of data from the many longitudinal studies conducted internationally, a high likelihood of phenotypic heterogeneity may prohibit harmonisation and ana...

Background Amnestic initial symptoms are common in Alzheimer’s disease(AD). However initial non‐amnestic (language, executive or visuospatial) symptoms are seen in ∼20% and associated with faster progression. Given racial differences in clinical and biomarker characteristics in AD, we explored if initial cognitive symptoms differed by race of the p...

Background Although high‐throughput DNA/RNA sequencing technologies have generated massive genetic and genomic data in human disease, translation of these findings into new patient treatment has not materialized by lack of effective approaches, such as Artificial Intelligence (AL) and Machine Learning (ML) tools. Method To address this problem, we...

Background Microglia have been implicated as a key aspect of the pathology of Alzheimer’s disease (AD). However, high microglial heterogeneities, including disease‐associated microglia (DAM), tau microglia (tau‐pathology related), and neuroinflammation‐like microglia (NIM), hinder the development of microglia‐targeted treatment. Method In this stu...

Background The emerging tools of protein‐protein interactome network offer a platform to explore not only the molecular complexity of human diseases, but also to identify risk genes and drug targets. Integration of the genome, transcriptome, proteome, and the interactome networks are essential for such identification, including Alzheimer’s disease...

Investigating the mechanism of differentiating similar representations, known as pattern separation, has primarily focused on the hippocampus. The roles of cortical regions and their interaction with the hippocampus remain largely unclear. In this study, we address this topic by analyzing whole-brain, high-resolution mnemonic similarity task (MST)...

INTRODUCTION High microglial heterogeneities hinder the development of microglia‐targeted treatment for Alzheimer's disease (AD). METHODS We integrated 0.7 million single‐nuclei RNA‐sequencing transcriptomes from human brains using a variational autoencoder. We predicted AD‐relevant microglial subtype‐specific transition networks for disease‐assoc...

Background Rapidly progressive Alzheimer's disease (rpAD) is a clinical subtype distinguished by its rapid cognitive decline and shorter disease duration. rpAD, like typical AD (tAD), is characterized by underlying neuropathology of amyloid plaques and neurofibrillary tangles. There is early evidence that the composition of amyloid plaques could va...

INTRODUCTION Transposable element (TE) dysregulation is associated with neuroinflammation in Alzheimer's disease (AD) brains. Yet, TE quantitative trait loci (teQTL) have not been well characterized in human aged brains with AD. METHODS We leveraged large‐scale bulk and single‐cell RNA sequencing, whole‐genome sequencing (WGS), and xQTL from three...

Background Alzheimer’s disease (AD) is the most common form of dementia characterized by amyloid beta (Abeta) plaques and neurofibrillary tau tangles in the brain. Cerebrospinal fluid (CSF) biomarkers Abeta42, total tau (tTau), and phosphorylated tau (pTau181) offer a high degree of sensitivity and specificity in the diagnosis of AD and have utilit...

Introduction Informed decisions to enrol in the clinical investigations of Alzheimer’s disease and related dementias (ADRD) require careful consideration of complex risks and uncertain benefits. Decisions regarding whether to receive information about biomarker status are complicated by lack of scientific consensus regarding biomarkers as surrogate...

Background and Objectives It is widely cited that dementia occurs in up to 80% of patients with Parkinson disease (PD), but studies reporting such high rates were published over two decades ago, had relatively small samples, and had other limitations. We aimed to determine long-term dementia risk in PD using data from two large, ongoing, prospectiv...

Although human cerebellum is known to be neuropathologically impaired in Alzheimer’s disease (AD) and AD-related dementias (ADRD), the cell type-specific transcriptional and epigenomic changes that contribute to this pathology are not well understood. Here, we report single-nucleus multiome (snRNA-seq and snATAC-seq) analysis of 103,861 nuclei isol...

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder. However, current treatments are directed at symptoms and lack ability to slow or prevent disease progression. Large-scale genome-wide association studies (GWAS) have identified numerous genomic loci associated with PD, which may guide the development of disease-modify...

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...

Introduction: Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) deposition in brain vessels, leading to hemorrhagic phenomena and cognitive impairment. Magnetic resonance imaging (MRI)-based criteria allow a diagnosis of probable CAA in vivo, but such a diagnosis cannot predict the eventual development of CAA. Methods: We cond...

In addition to Alzheimer’s disease (AD), the hippocampus is now known to be affected in variants of frontotemporal degeneration (FTD). In semantic variant primary progressive aphasia (svPPA), characterized by language impairments, hippocampal atrophy is greater in the left hemisphere. Nonverbal impairments (e.g., visual object recognition) are prom...

INTRODUCTION Cerebral amyloid angiopathy (CAA) often accompanies dementia‐associated pathologies and is important in the context of anti‐amyloid monoclonal therapies and risk of hemorrhage. METHODS We conducted a retrospective neuropathology‐confirmed study of 2384 participants in the National Alzheimer Coordinating Center cohort (Alzheimer's dise...

As a protective measure, organizations should perform regular data risk assessments to review and protect sensitive information. But what is a data risk assessment and what are good ways to perform it?

The high failure rate of clinical trials in Alzheimer’s disease (AD) and AD-related dementia (ADRD) is due to a lack of understanding of the pathophysiology of disease, and this deficit may be addressed by applying artificial intelligence (AI) to “big data” to rapidly and effectively expand therapeutic development efforts. Recent accelerations in c...

Despite its high prevalence among dementias, Lewy body dementia (LBD) remains poorly understood with a limited, albeit growing, evidence base. The public‐health burden that LBD imposes is worsened by overlapping pathologies, which contribute to misdiagnosis, and lack of treatments. For this report, we gathered and analyzed public‐domain information...

Background The criteria for diagnosis of dementia with Lewy bodies (DLB) remain predominantly clinical. However, use of striatal dopamine transporter visualization is suggested as an “indicative” biomarker for DLB under the most recent published DLB criteria (McKeith, Neurology, 2017). The objective of this study is to determine if 123I‐ioflupane S...

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 Transposable elements (TEs), known as “jumping genes” or “viral elements”, constitute approximately 45% of the human genome. However, transposable element (TE) dysregulation of quantitative trait loci (QTL) has not been well‐characterized in human disease, such as Alzheimer’s disease (AD). Method In this study, we present the first cata...

Background Mild cognitive impairment (MCI) reflects cognitive deficits without significant functional decline in activities of daily living. MCI subtypes correspond to phenotypic cognitive impairment patterns in memory, attention, language, executive, and visuospatial compared to age‐adjusted norms: Amnestic single domain (ASD) or multi‐domain (AMD...

Background Cerebrospinal fluid (CSF) biomarkers for amyloid (A), tau (T), and neurodegeneration (N) can be utilized to define pre‐mortem pathological status (ATN research framework). However, potential differences across methods present challenges when comparing studies. Our objective was to determine the ATN status in an AD/ADRD cohort using two d...

Background Although Alzheimer’s disease (AD) is sexually dimorphic in prevalence, incidence, symptomology, and neuropathology, the molecular mechanisms underlying AD sex differences are incompletely understood. Method In this study, we investigated the interplay between cellular metabolism and immune responses (termed the “ immunometabolism endoph...

Background Translation of massive genetic and genomic data into Alzheimer’s target and drug discovery has not materialized. One challenge in this process is ethnicity‐based differences in the field of Alzheimer’s disease (AD). For example, African Americans (AAs) and European Americans (EAs) differ in AD prevalence, risk factors, and symptomatic pr...

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 Resting state functional connectivity measured with MRI (rsfMRI) is disrupted in Alzheimer’s Disease (AD), although reports of rsfMRI changes in adults with the apolipoprotein E ( APOE ) ε4 genotype (e4+) have been inconsistent. Here, we compare default mode network (DMN) connectivity between e4+ and non‐carriers (e4‐) groups and assess...

Background Microglia have been implicated in the pathophysiology of Alzheimer’s disease (AD) for over 100 years, and substantial progress has been made in characterizing microglial heterogeneities and biology, including disease‐associated microglia (or DAM, amyloid‐pathology related, neuro‐protective), tau microglia (tau‐pathology related), and inf...

Background Mild cognitive impairment (MCI) reflects cognitive deficits without significant functional decline in activities of daily living. MCI subtypes correspond to phenotypic cognitive impairment patterns in memory, attention, language, executive, and visuospatial compared to age‐adjusted norms: Amnestic single domain (ASD) or multi‐domain (AMD...

Background Mild cognitive impairment (MCI) reflects cognitive deficits without significant functional decline in activities of daily living (1). MCI subtypes correspond to phenotypic cognitive impairment patterns in memory, attention, language, executive, and visuospatial compared to age‐adjusted norms: Amnestic single domain (ASD) or multi‐domain...

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 Informed decisions to enroll in clinical investigations of Alzheimer’s disease and related dementias (ADRD) require careful consideration of complex risks and uncertain benefits. Decisions regarding scope of research participation and whether to receive information about biomarker status are complicated by lack of scientific consensus re...

Background Dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) are the among the most common neuropathologies. Amyloid and tau biomarker changes are often incorporated in the clinical diagnosis of AD. The current DLB criteria does not include robust biofluid biomarkers. However differences in amyloid plaque and CSF neurogranin in DLB has b...

Lewy body dementia is the second most common neurodegenerative dementia after Alzheimer’s disease. Disease-modifying therapies for this disabling neuropsychiatric condition are critically needed. To identify drugs associated with risk of developing Lewy body dementia, we performed a population-based case-control study of 148,170 United States Medic...

INTRODUCTION The molecular mechanisms that contribute to sex differences, in particular female predominance, in Alzheimer's disease (AD) prevalence, symptomology, and pathology, are incompletely understood. METHODS To address this problem, we investigated cellular metabolism and immune responses (“immunometabolism endophenotype”) across AD individ...

In 2022, Bruce Willis’ family released a statement saying that he had been diagnosed with aphasia (an acquired language impairment) and would no longer be acting. Ten months later, the Willis family released another statement indicating that he received a more specific diagnosis of frontotemporal degeneration (FTD). This resulted in an explosion of...

Objective Pareidolias represent visual illusions of meaningful objects in ambiguous stimuli. Prior research has demonstrated phenomenological similarities between pareidolias and visual hallucinations (VH) and the potential clinical utility of pareidolias in discriminating dementia with Lewy bodies (DLB) from Alzheimer’s dementia (ad). Though parei...

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...

Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in non-European ancestry groups in genome-wide association studies (GWAS). We constructed and analyzed a multi-ancestry GWAS dataset in the Alzheimer Disease (AD) Genetics Consortium (ADGC) to test for novel shared and ancestry-specific AD susceptibility loc...

We characterized the role of structural variants, a largely unexplored type of genetic variation, in two non-Alzheimer's dementias, namely Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced structural variant calling pipeline (GATK-SV) to short-read whole-genome sequenc...

Background The relationship between biomarkers of metabolic syndrome and insulin resistance, plasma triglyceride/HDL cholesterol (TG/HDL-C) ratio, on the rate of cognitive decline in mild cognitive impairment (MCI) and dementia stages of Alzheimer’s disease (AD) is unknown. The role of peripheral and cerebrospinal fluid (CSF) levels of Apolipoprote...

Background The self-administered iPad-based Cleveland Clinic Cognitive Battery (C3B) was designed specifically for the efficient screening of cognitive functioning of older adults in a primary care setting. Objective 1) Generate regression-based norms from healthy participants to enable demographic corrections to facilitate clinical interpretation...

Unlabelled: The regulatory path for drug approval is increasingly well defined. Drugs for the treatment of Alzheimer disease (AD) need to show statistically significant benefit over placebo with respect to cognitive and functional measures, with the Clinical Dementia Rating scale and Alzheimer's Disease Assessment Scale-Cognitive Subscale being am...

Introduction: The relationship between initial cognitive symptoms and subsequent rate of clinical decline is important in clinical care and the design of dementia clinical trials. Methods: This retrospective longitudinal, autopsy-confirmed, cohort study among 2426 participants in the National Alzheimer's Coordinating Center database included Alz...

Although Alzheimer’s disease (AD) is sexually dimorphic in prevalence, incidence, symptomology, and neuropathology, the molecular mechanisms underlying these sex differences are not well understood. We presented a multimodal omics analytic framework to inspect sex differences in susceptibility to inflammation, cellular metabolism, and disease patho...

Transposable elements (TEs), known colloquially as “jumping genes” or “viral elements”, constitute approximately 45% of the human genome. Recent evidences showed that TEs are activated in AD by age‐associated epigenetic alterations or retroviral infection; yet, mechanisms of AD‐risk TE activation remain elusive. We investigated TE activation underl...

Discerning Dementia with Lewy Bodies (DLB) from Alzheimer's disease (AD) can be a challenge for the clinician and represents a critical unmet medical need. Diagnosis of DLB is especially challenging in early stages due to variable core features and coexistent pathologies such as AD. A variable immune response has been implicated in AD/ADRD. Soluble...

Human genome sequencing studies have identified numerous loci associated with complex diseases, including Alzheimer’s disease (AD). However, translating human genetic and genomic findings (i.e., genome‐wide association studies [GWAS]) to pathobiology and therapeutic discovery remains a major challenge. Today, artificial intelligence and deep learni...

Diagnostic guidelines currently exist for typical and atypical Alzheimer’s disease (AD). Significant heterogeneity exists among initial predominant clinical symptoms among Lewy body‐related pathology (LRP) in addition to primary AD pathology (ADP) and. However, the clinical relevance of initial amnestic or non‐amnestic cognitive symptoms among them...

An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases w...

Elevated incidences of Alzheimer’s disease (AD) and disease progression may be associated with African American (AA)‐specific disease comorbidities, such as hypertension, diabetes, and chronic kidney disease. Treatments and management of these comorbidities — such as antihypertensive angiotensin‐II receptor blockers (ARBs) — may reduce risk of AD i...

Recent advances in massive single‐cell/nucleus (sc/sn) transcriptomic data have great potential for identification of cell‐type specific Alzheimer’s disease (AD) pathobiology, as well as target discovery for drug repurposing. We designed and implemented a multimodal omics analytic framework for the processing of sc/sn transcriptomic datasets, analy...

Drug repositioning and repurposing has proved useful in identifying new treatments for many diseases, which can then rapidly be brought into clinical practice. Currently, there are few effective pharmacological treatments for Lewy body dementia (which includes both dementia with Lewy bodies and Parkinson’s disease dementia) apart from cholinesteras...

Introduction African Americans (AAs) and European Americans (EAs) differ in Alzheimer's disease (AD) prevalence, risk factors, and symptomatic presentation and AAs are less likely to enroll in AD clinical trials. Methods We conducted race‐conscious pharmacoepidemiologic studies of 5.62 million older individuals (age ≥60) to investigate the associa...

Translating human genetic findings (genome-wide association studies [GWAS]) to pathobiology and therapeutic discovery remains a major challenge for Alzheimer’s disease (AD). We present a network topology-based deep learning framework to identify disease-associated genes (NETTAG). We leverage non-coding GWAS loci effects on quantitative trait loci,...

Dementia with Lewy bodies (DLB) is clinically defined by the presence of visual hallucinations, fluctuations, rapid eye movement (REM) sleep behavioral disorder, and parkinsonism. Neuropathologically, it is characterized by the presence of Lewy pathology. However, neuropathological studies have demonstrated the high prevalence of coexistent Alzheim...

Introduction: Recent advances in generating massive single-cell/nucleus transcriptomic data have shown great potential for facilitating the identification of cell type-specific Alzheimer's disease (AD) pathobiology and drug-target discovery for therapeutic development. Methods: We developed The Alzheimer's Cell Atlas (TACA) by compiling an AD br...

Accumulating evidence suggests that gut-microbiota metabolites contribute to human disease pathophysiology, yet the host receptors that sense these metabolites are largely unknown. Here, we developed a systems pharmacogenomics framework that integrates machine learning (ML), AlphaFold2-derived structural pharmacology, and multi-omics to identify di...

Alzheimer's disease (AD) has been linked to multiple immune system-related genetic variants. Triggering receptor expressed on myeloid cells 2 (TREM2) genetic variants are risk factors for AD and other neurodegenerative diseases. In addition, soluble TREM2 (sTREM2) isoform is elevated in cerebrospinal fluid in the early stages of AD and is associate...

The APOE locus is strongly associated with risk for developing Alzheimer's disease and dementia with Lewy bodies. In particular, the role of the APOE ϵ4 allele as a putative driver of α-synuclein pathology is a topic of intense debate. Here, we performed a comprehensive evaluation in 2466 dementia with Lewy bodies cases versus 2928 neurologically h...

Background: The criteria for PD-MCI allow the use of global cognitive tests. Their predictive value for conversion from PD-MCI to PDD, especially compared to comprehensive neuropsychological assessment, is unknown. Methods: The MDS PD-MCI Study Group combined four datasets containing global cognitive tests as well as a comprehensive neuropsychol...

Background and objectives: Evaluating and understanding the heterogeneity in dementia course has important implications for clinical practice, healthcare decision-making, and research. However, inconsistent findings have been reported with regard to the disease courses of the two most common dementias, Alzheimer's disease (AD) and Dementia with Le...

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 ris...

Genetics play an important role in late-onset Alzheimer’s Disease (AD) etiology and dozens of genetic variants have been implicated in AD risk through large-scale GWAS meta-analyses. However, the precise mechanistic effects of most of these variants have yet to be determined. Deeply phenotyped cohort data can reveal physiological changes associated...

Importance: Behavioral and psychological symptoms of dementia (BPSDs) in association with amnestic and nonamnestic cognitive phenotypes have not been evaluated across diagnoses of Alzheimer disease pathology (ADP), Lewy body-related pathology (LRP), and mixed pathology (ADP-LRP). Objectives: To determine the clinical phenotypes at the initial vi...

The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLBs) and Parkinson's disease dementia (PDD). The meeting featured eight internationally known scientists from Eu...

Background Genome-wide association studies (GWAS) have identified numerous susceptibility loci for Alzheimer’s disease (AD). However, utilizing GWAS and multi-omics data to identify high-confidence AD risk genes (ARGs) and druggable targets that can guide development of new therapeutics for patients suffering from AD has heretofore not been success...

In 2019, the Lewy Body Dementia Association formed an Industry Advisory Council to bring together a collaborative group of stakeholders with the goal of accelerating clinical research into Lewy body dementia treatments. At the second annual meeting of the Industry Advisory Council, held virtually on June 18, 2020, the key members presented ongoing...

Background Alzheimer’s disease (AD) is the 6th leading cause of death in the US, and currently lacks a blood‐based biomarker for early detection. Triggering receptor expressed on myeloid cells 2 (TREM2) is an immune regulator shown to be protective against AD; a soluble form (sTREM2) circulates in peripheral blood and is a potential indicator of di...

Background: Systematic identification of molecular networks in disease relevant immune cells of the nervous system is critical for elucidating the underlying pathophysiology of Alzheimer's disease (AD). Two key immune cell types, disease-associated microglia (DAM) and disease-associated astrocytes (DAA), are biologically involved in AD pathobiolog...

Dementia with Lewy bodies (DLB) research has seen a significant growth in international collaboration over the last three decades. However, researchers face a challenge in identifying large and diverse samples capable of powering longitudinal studies and clinical trials. The DLB research community has begun to focus efforts on supporting the develo...

The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy Body Dementia (LBD), which includes Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD). The meeting featured eight internationally known scientists from Eur...

Alzheimer's disease (AD) has been linked to multiple immune system genetic variants, implicating potential broad alterations in inflammatory profiles in the disease. Triggering receptor expressed on myeloid cells 2 (TREM2) genetic variants are risk factors for AD and other neurodegenerative diseases. A soluble TREM2 isoform (sTREM2) is elevated in...

Studies of resting-state functional connectivity MRI in Alzheimer’s disease suggest that disease stage plays a role in functional changes of the default mode network. Individuals with the genetic disorder Down syndrome show an increased incidence of early-onset Alzheimer’s-type dementia, along with early and nearly universal neuropathologic changes...

Introduction: Mid-life dietary patterns are associated with Alzheimer's disease (AD) risk, although few controlled trials have been conducted. Methods: Eighty-seven participants (age range: 45 to 65) with normal cognition (NC, n = 56) or mild cognitive impairment (MCI, n = 31) received isocaloric diets high or low in saturated fat, glycemic inde...

Inflammatory changes are among the key markers of Alzheimer's disease (AD) related pathological changes. Pro-inflammatory analytes have been related to cognitive decline while others have been related to attenuating neuronal death. Among them, changes in cerebrospinal fluid (CSF) levels of soluble triggering receptor expressed on myeloid cells 2 (s...

Background Dementia-like cognitive impairment is an increasingly reported complication of SARS-CoV-2 infection. However, the underlying mechanisms responsible for this complication remain unclear. A better understanding of causative processes by which COVID-19 may lead to cognitive impairment is essential for developing preventive and therapeutic i...

Background There is significant interest in understanding the role of modifiable vascular risk factors contributing to dementia risk across age groups. Objective Risk of dementia onset was assessed in relation to vascular risk factors of hypertension and hypercholesterolemia among cognitively normal APOE ɛ4 carriers and non-carriers. Methods In a...

Introduction Although sleep disruption in Alzheimer’s disease (AD) pathogenesis has been described, the role of circadian rhythm dysfunction (CRD) is less understood. We hypothesize greater CRD and sleep disruption with poorer cognitive function in AD compared to normal cognition. Methods We examined 3 groups:1)mild cognitive impairment with posit...

Zonisamide is an anti-epileptic medication with multiple mechanisms of action and a favorable safety profile. Zonisamide may interact with Lewy body dementia pathophysiology through a mechanism unrelated to its original indication. Zonisamide has shown efficacy as adjunct therapy for the management of motor symptoms in patients with Parkinson’s dis...