Emerging evidence has connected Alzheimer's disease (AD) to systemic inflammation, intestinal abnormalities, and altered gut microbiota, highlighting the significance of the gut–brain axis. Here, we investigated the impact of acute experimental colitis (acute colitis) on AD pathology.

Widespread use of retinal optical coherence tomography angiography (OCT-A) imaging requires methodological and analytical consensus to ensure reproducible and accurate results in epidemiological studies on Alzheimer's disease and related dementias (ADRD).

Alzheimer's & Dementia publishes a set of papers exploring the diagnostic and prognostic capabilities of a novel cutting-edge multiplexed biomarker measurement technology across neurodegenerative dementias.

Dementia impairs driving skills, but the specific driving behaviors affected are not fully understood. This project reviewed the literature on driving behaviors more common among people with dementia compared to age-matched healthy controls. A search of Scopus, Medline All, and Embase databases (1994 to September 2024) identified relevant studies. Articles were included if they addressed driving behaviors

The morphological and molecular changes associated with the degeneration of arterioles in cerebral amyloid angiopathy (CAA) are incompletely understood.

We addressed whether higher education plays a causal role in reducing dementia risk by comparing two indices of cognitive reserve: education and young adult general cognitive ability (GCA).

Synapse loss is a key driver of cognitive decline in Alzheimer's disease (AD), yet its direct relationship with neurofibrillary tau tangle (NFT) burden remains unclear. This study leveraged positron emission tomography (PET) imaging to investigate the link between NFT accumulation and synaptic density in older adults with and without AD pathology.

Alzheimer's disease (AD) plasma biomarkers are non-invasive measures of the key amyloid beta (Aβ) and tau pathologies. Validation and generalization studies are needed to fully understand their potential for AD prediction and diagnosis in the elderly population.

Analyzing the proteomes of different brain cell types is fundamental for understanding the pathophysiology of Alzheimer's disease (AD). However, spatial analysis of these diverse and limited cell populations poses significant challenges.

We aimed to examine the global impact of brain small vessel disease (SVD) on cognitive performance.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by macroscopic features such as cortical atrophy, narrowing of the gyri, widening of the sulci, and enlargement of the ventricles. At the cellular level, the pathological characteristics include the extracellular aggregation of β-amyloid (Aβ) forming senile plaques, and the intracellular accumulation of hyperphosphorylated tau proteins

Alzheimer’s disease (AD) is a complex neurodegenerative disorder that is characterized by the accumulation of pathologic tau and beta-amyloid proteins. UFMylation is an emerging ubiquitin-like post-translational modification that is crucial for healthy brain development. The UFM1 cascade was recently identified as a major modifier of tau aggregation in vitro and in vivo. Moreover, post-mortem AD brain

Alzheimer’s disease (AD) is characterized by amyloid plaques, neurofibrillary tangles, and synaptic and neuronal loss. Recently, a rare autosomal dominant coding mutation, T835M, in the Un-coordinated 5c (UNC5C) netrin receptor gene was segregated with late-onset AD (LOAD). Overexpression of T835M in primary hippocampal neurons increased cell death in response to neurotoxic stimuli including beta-amyloid

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative disorders with overlapping clinical, genetic and pathological features. A large body of evidence highlights the critical role of RNA-binding proteins (RBPs) – in particular TAR DNA-binding protein 43 (TDP-43) and Fused in sarcoma (FUS) – in the pathogenesis of these diseases. These RBPs normally

Polymorphisms in the gene encoding CD2-associated protein (CD2AP) are associated with an increased risk for developing Alzheimer’s disease (AD). Intriguingly, variants in the gene also cause a pattern of kidney injury termed focal segmental glomerulosclerosis. Recent studies have investigated the cell types and mechanisms by which CD2AP gene dosage contributes to the key pathological features of AD

INTRODUCTIONThe study aimed to develop and validate the Emergency Department Dementia Algorithm (EDDA) to detect dementia among older adults (65+) and support clinical decision‐making in the emergency department (ED).METHODSIn a multisite retrospective study of 759,665 ED visits, electronic health record data from Yale New Haven Health (2014–2022) were used to train three supervised and semi‐unsupervised

Drawing on two decades of clinical experience with affective disorders, Jesús Ramírez-Bermúdez— runner up in the Brain Essay Competition 2024—explores the cultural significance of melancholy, with the aid of historical archives from the Inquisition and the introspections of a 17th century poet.

Matt Butler, runner up in the Brain Essay Competition 2024, considers what happens when memories fragment and certainties fade in this fictional tale of a professor of literature who loses her grasp on time.

BackgroundHereditary ataxias are genetically diverse, yet up to 75% remain undiagnosed due to technological and financial barriers. The GGC repeat expansion in ZFHX3, responsible for spinocerebellar ataxia type 4 (SCA4), has only been described in individuals of Northern Europeandescent.ObjectiveUncover the genetic etiology of suspected hereditary movement disorders.MethodsWe performed Oxford Nanopore

ImportancePrevious studies have described a potential association between epilepsy and frontotemporal dementia (FTD), but no systematic data are available.ObjectiveTo determine whether epilepsy is more prevalent in patients with FTD than in healthy controls (HCs) or patients with Alzheimer disease (AD).Design, Setting, and ParticipantsIn this case-control study, we compared the prevalence of epilepsy

This study investigates outcomes in patients undergoing surgery for chronic subdural hematoma comparing those receiving vs not receiving antithrombotic therapy.

ImportanceMidlife vascular risk factors are associated with an elevated risk of dementia. However, the total contribution of vascular risk factors in midlife and late life with incident dementia is uncertain.ObjectiveTo quantify the proportion of incident dementia attributable to modifiable vascular risk factors measured in midlife and late life and to examine differences by apolipoprotein ε4 genotype

The historical understanding of cerebrospinal fluid (CSF) production and flow comprises CSF production primarily in the choroid plexus of the 1st-3rd ventricles, flow through the aqueduct of Sylvius en route to the 4th ventricle, circulation around the subarachnoid space, and ultimately resorption into the blood circulation through arachnoid granulations. Since the discovery of a perivascular CSF clearance

Apathy is a common neuropsychiatric symptom (NPS) in Alzheimer’s disease (AD) but can emerge earlier in prodromal and even preclinical stages as part of mild behavioural impairment (MBI-apathy), a syndrome defined by emergent and persistent NPS. In dementia, apathy is associated with higher morbidity, mortality, and caregiver distress. However, the significance of MBI-apathy in dementia-free persons

Monoallelic pathogenic variants in LGI1 cause autosomal dominant epilepsy with auditory features with onset in childhood/adolescence. LGI1 is a secreted neuronal protein, functions as a ligand for ADAM22/23, and regulates excitatory synaptic transmission and neuronal excitability in the brain. While biallelic ADAM22 variants cause developmental and epileptic encephalopathy (DEE), the whole picture

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β plaques, tau hyperphosphorylation, and neuroinflammation. The choroid plexus (ChP), serving as the blood-cerebrospinal fluid-brain barrier, plays essential roles in immune response to stress and brain homeostasis. However, the cellular and molecular contributions of the ChP to AD progression

INTRODUCTIONThis study assessed the heterogeneous treatment effects (HTEs) of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) on the risk of Alzheimer's disease and related dementias (ADRD).METHODSThis target trial emulation study included adults (≥ 50 years) with type 2 diabetes (T2D) and newly prescribed a GLP‐1RA, SGLT2i, or other second‐line

INTRODUCTIONEnd‐of‐life (EOL) caregiving is associated with stress and burden, especially for persons with dementia. Little is known, however, about how dementia diagnosis, family structure, and co‐residence influence the prevalence of antidepressants and anxiolytics (psychiatric prescriptions) among spouses and adult children during EOL caregiving.METHODSThis was a retrospective cohort study of spouses

INTRODUCTIONDementia family caregivers face a significant burden due to the progressive nature of the disease, which places them at high risk for depression. Because a lack of information is available on the social determinants of health that impact depression, this study investigated this relationship.METHODSThis study was a secondary data analysis using the 2017 National Health and Aging Trends Study

BackgroundFunctional speech disorder (FND‐speech) is a subtype of functional neurological disorder, yet quantitative characterization of its motor and cognitive‐linguistic features remains underexplored.ObjectiveThis study aimed to quantitatively characterize FND‐speech by comparing acoustic and linguistic features in individuals with FND‐speech with healthy control subjects (HCs). The potential of

BackgroundIn some patients with parkinsonism and abnormal dopamine transporter (DAT) imaging using [123I]FP‐CIT single‐photon emission computed tomography (SPECT), subsequent clinical evolution does not fit well with a neurodegenerative diagnosis.ObjectiveThe objective was to analyze the results of positron emission tomography (PET) with the recently developed DAT radioligand [18F]FE‐PE2I in patients

INTRODUCTIONWe report the feasibility and cognitive outcomes of a stage 1b randomized trial testing 3 months of home‐delivered high polyphenol snacks (e.g., nuts, berries) and online speed of processing training among older adults with 12 or fewer years of education.METHODSOne hundred eighty participants were randomized to polyphenol‐rich snacks and online cognitive training, polyphenol snacks and

INTRODUCTIONHeterogeneity of clinical progression in Alzheimer's disease (AD) complicates the assessment of disease progression and treatment effects in trials. This study evaluates the potential of plasma phosphorylated tau‐217 (p‐tau217) to capture this heterogeneity.METHODSWe used k‐means clustering to analyze cognitive trajectories in amyloid beta –positive (Aβ+) cognitively normal (CN) and mild

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a preCGG repeat expansion in the FMR1 gene. Individuals with the FMR1 premutation often exhibit neuropsychiatric symptoms before FXTAS onset, leading to the identification of fragile X-associated neuropsychiatric disorders (FXAND). Rodent models of FXTAS show motor impairments, pathological intranuclear

BackgroundStimulation‐induced dyskinesias (SID) from deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) are uncommon; however, they are increasingly recognized. Once considered transient and indicative of effective neuromodulation, SID are now seen as potential therapy‐limiting side effects, akin to internal capsule activation. The mechanism and anatomical

BackgroundExcessive daytime sleepiness (EDS) is a disabling symptom of Lewy body disorders (LBD). The hypothalamus is a key sleep–wake regulator and is involved in Lewy pathology, but its contribution to EDS in LBD remains unclear.ObjectivesTo use diffusion‐weighted magnetic resonance imaging (MRI) to detect hypothalamic microstructure and determine its relationship to EDS symptoms in LBD in an exploratory

BackgroundParkinson disease (PD) disease‐modifying therapy (DMT) trials generally recruit individuals from teaching hospitals. Whether these participants represent the broader PD population is unclear.ObjectiveThe objective was to compare individuals with PD seen by neurologists in teaching hospitals early in their disease—a proxy for DMT trial‐eligible cohorts—with individuals seen in other settings

Alzheimer’s disease (AD) is increasingly recognized as a systemic disorder with a substantial metabolic disorder component, where the liver significantly impacts the brain via the liver-brain axis. Key mechanisms include the liver’s role in clearing peripheral β-amyloid (Aβ), the influence of hepatic enzymes and metabolites on cognitive decline, and the systemic effects of metabolic disorders on AD

Recent years have seen major advances in tau‐associated brain disorders through interdisciplinary research spanning molecular biology, neuroimaging, clinical trials, and therapeutic development. The Tau2024 Global Conference, hosted by the Alzheimer's Association, CurePSP, and Rainwater Charitable Foundation, showcased these efforts by bringing together researchers and experts worldwide to discuss

Dilmore AH, Martino C, Neth BJ, et al. Effects of a ketogenic and low-fat diet on the human metabolome, microbiome, and foodome in adults at risk for Alzheimer's disease. Alzheimer's Dement. 2023;4805-4816. https://doi.org/10.1002/alz.13007 The Conflict of Interest Statement is incomplete. The full Conflict of Interest Statement should be: Rima Kaddurah-Daouk is an inventor of key patents in the field

A number of neuropeptides including pituitary adenylate cyclase-activating polypeptide (PACAP) play an important role in the pathophysiology of migraine. Infusions of PACAP in patients with migraine can provoked migraine attacks. A placebo-controlled study with a monoclonal antibody directed against the PACAP-receptor failed to show efficacy. In a small, short, proof of concept study a monoclonal antibody

Neuroimaging with positron emission tomography (PET) has been instrumental in elucidating neurobiological mechanisms behind therapeutical trials in Parkinson's disease (PD). A variety of medical and neurosurgical interventions have been evaluated using many radioligands that reveal molecular basis for target engagement and brain responses in relation to clinical outcome measures. This review article

BackgroundPlasma phosphorylated tau181 (pTau181) is proving to be a useful predictor of Alzheimer's disease (AD). AD co‐pathology is frequently observed across the Lewy body disease (LBD) spectrum.ObjectiveTo determine whether pTau181 in LBD is associated with postmortem Alzheimer's disease neuropathologic changes (ADNC) and with antemortem positron emission spectrometry measurements of β‐amyloid and

Asparagine endopeptidase (AEP) is implicated in the pathogenesis of Alzheimer’s disease (AD) by cleaving Tau at residue N368, accelerating its hyperphosphorylation and aggregation. The Tau N368/t-Tau ratio in cerebrospinal fluid (CSF) serves as a superior biomarker compared to established biomarkers (p-Tau 181/217) for correlating with tau pathology and synaptic dysfunction in patients with AD, highlighting

INTRODUCTIONWe investigated the associations of longitudinal synaptic loss and cognitive decline with tau burden and plasma biomarkers in Alzheimer's disease (AD).METHODSTwenty cognitively impaired (CI) individuals and 16 healthy controls (HC) underwent cognitive and plasma biomarker assessments, amyloid positron emission tomography (PET), tau PET, and synaptic density PET; after 1 year, tau and synaptic

Targeting of tau pathology has long been proposed as a potential therapeutic strategy for Alzheimer’s disease (AD). Semorinemab is a humanized IgG4 monoclonal antibody that binds to all known isoforms of full-length tau with high affinity and specificity. Semorinemab’s safety and efficacy have been studied in two Phase 2 randomized, double-blind, placebo-controlled, parallel-group clinical trials:

Thalamic atrophy already occurs in the early stages of multiple sclerosis (MS) and continues progressively throughout the disease. Demyelination is one of the main pathological hallmarks of MS and yet, thalamic demyelination does not correlate well with thalamic atrophy. By combining post-mortem magnetic resonance imaging with immunohistochemistry of thalami from 13 control and 13 MS donors, we investigated

BACKGROUND AND OBJECTIVES Disturbed sleep is common after stroke, yet its relationship with cerebral small vessel disease (SVD) and cognitive performance in the stroke population, particularly patients with TIA/mild stroke who are on the milder end of the cerebrovascular spectrum, remains understudied. We aim to examine the associations of self-reported sleep metrics with neuroimaging markers of SVD

BackgroundObject‐location memory impairment in Huntington's disease (HD) occurs from premanifest period and declines as HD progresses, however, pathogenesis of object‐location memory is unknown. The striatum and hippocampus are affected in HD, functionally interacting allowing intact object‐location memory.ObjectivesThe present study investigated if object location memory impairment in premanifest

ImportanceRecent research suggests a plausible biological link between autism spectrum disorder (ASD) and Parkinson disease (PD). Nonetheless, large longitudinal studies examining the risk of PD following ASD are lacking.ObjectiveTo examine the association between ASD and future PD risk.Design, Setting, and ParticipantsA nationwide population-based prospective cohort study was performed using data