Neurofilament Light Chain and Differentiation of Behavioral Variant Frontotemporal Dementia From Psychiatric Disorders: A Systematic Review.

Importance: Behavioral variant frontotemporal dementia (bvFTD), the most common subtype of FTD, is a leading form of early-onset dementia worldwide. Accurate and timely diagnosis of bvFTD is frequently delayed due to symptoms overlapping with common psychiatric disorders, and interest has increased in identifying biomarkers that may aid in differentiating bvFTD from psychiatric disorders.

Objective: To summarize and critically review studies examining whether neurofilament light chain (NfL) in cerebrospinal fluid (CSF) or blood is a viable aid in the differential diagnosis of bvFTD vs psychiatric disorders.

Plasma lipidome dysregulation in frontotemporal dementia reveals shared, genotype-specific, and severity-linked alterations.

Introduction: Biomarkers are essential for monitoring the progression of frontotemporal dementia (FTD). Although dysregulated brain lipid metabolism, particularly sphingolipids enriched in the nervous system, is a key feature of neurodegeneration, plasma lipids remain underexplored as biomarkers compared to imaging and serum proteins.

Methods: We examined plasma lipidomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from individuals carrying pathogenic variants linked to autosomal dominant FTD (GRN, C9orf72, MAPT) and non-carriers.

Recent advances in neuroimaging of Alzheimer's disease and related dementias.

This review covers recent advances (2023-2024) in neuroimaging research into the pathophysiology, progression, and treatment of Alzheimer's disease (AD) and related dementias (ADRD). Despite the rapid emergence of blood-based biomarkers, neuroimaging continues to be a vital area of research in ADRD. Here, we discuss neuroimaging as a powerful tool to topographically visualize and quantify amyloid, tau, neurodegeneration, inflammation, and vascular disease in the brain.

A single-cell, long-read, isoform-resolved case-control study of FTD reveals cell-type-specific and broad splicing dysregulation in human brain.

Progranulin-deficient frontotemporal dementia (GRN-FTD) is a major cause of familial FTD with TAR DNA-binding protein 43 (TDP-43) pathology, which is linked to exon dysregulation. However, little is known about this dysregulation in glial and neuronal cells. Here, using splice-junction-covering enrichment probes, we introduce single-nuclei long-read RNA sequencing 2 (SnISOr-Seq2), targeting 3,630 high-interest genes without loss of precision, and complete the first single-cell, long-read-resolved case-control study for neurodegeneration.

Moderating effects of plasma glial fibrillary acidic protein along the Alzheimer's disease continuum.

Introduction: Glial fibrillary acidic protein (GFAP) may contribute to Alzheimer's pathology at early disease stages. GFAP moderation of Alzheimer's disease (AD)-related neurodegeneration and cognition is unclear.

Methods: We examined plasma GFAP moderation of AD biomarkers (amyloid beta [Aβ]-positron emission tomography [PET][A]; plasma phosphorylated tau-181 [p-tau181][T]), neurodegeneration (plasma NfL[N]; structural magnetic resonance imaging [MRI][N]), and cognition (Cog; Cog) in two cohorts: University of California San Francisco (UCSF) (N = 212, 91.

The National Dementia Workforce Study: Development of Questionnaires for Home Care, Assisted Living, and Nursing Home Settings.

The growing aging population and rising prevalence of dementia are driving increased demand for long-term care services and supports in the United States. People with dementia require substantial support and care, often from direct care workers in private homes, assisted living communities, and nursing homes. Despite their crucial role, these workers receive highly variable training, particularly in dementia care, and face significant work-related challenges including stress, injury, and burnout.

CSF total tau as a proxy of synaptic degeneration.

Cerebrospinal fluid (CSF) total tau (t-tau) is considered a biomarker of neuronal degeneration alongside brain atrophy and fluid neurofilament light chain protein (NfL) in biomarker models of Alzheimer's disease (AD). However, previous studies show that CSF t-tau correlates strongly with synaptic dysfunction/degeneration biomarkers like neurogranin (Ng) and synaptosomal-associated protein 25 (SNAP25). Here, we compare the association between CSF t-tau and synaptic degeneration and axonal/neuronal degeneration biomarkers in cognitively unimpaired and impaired groups from two independent cohorts.

Distinct manifestations of excitatory-inhibitory imbalance associated with amyloid-β and tau in patients with Alzheimer's disease.

A growing body of evidence shows that epileptic activity is frequently observed in patients with Alzheimer's disease (AD), implicating underlying excitatory-inhibitory imbalance. The distinction of whether the AD-epileptic phenotype represents a subset of patients or an underdiagnosed manifestation holds major therapeutic implications. Here, we quantified the excitatory-inhibitory imbalance in AD patients using magnetoencephalography and examined the relationships to AD pathophysiology-amyloid-beta and tau, and to epileptic activity.

Concurrent Changes in Plasma Phosphorylated Tau 217, Tau PET, and Cognition in Preclinical Alzheimer Disease.

Importance: Developing disease-modifying treatments is a priority for Alzheimer disease research.

Objective: To determine the potential of plasma phosphorylated tau 217 (p-tau217) and tau positron emission tomography (PET) to assess disease modification in treatment trials.

Design, Setting, And Participants: This diagnostic/prognostic study used longitudinal data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study collected from April 2014 to June 2023.

Cardiovascular contributions to dementia: Examining sex differences and female-specific factors.

Growing evidence underscores the importance of cardiovascular contributions to Alzheimer's disease and related dementias (AD/ADRD). While sex differences in cardiovascular disease (CVD) risk factors and outcomes are well established, the question of whether vascular contributions to AD/ADRD vary by sex has only recently garnered attention. In this narrative review, we discuss sex differences in conventional CVD risk factors (e.

Nasal Aβ42 mirrors brain amyloid dynamics and cognitive decline across the Alzheimer's disease continuum.

Early, non-invasive assessment of Alzheimer's disease (AD) progression remains a key challenge. This study evaluated whether nasal amyloid-β42 (Aβ42) levels reflect brain amyloid dynamics and cognitive decline. Nasal discharge from 161 individuals, ranging from cognitively unimpaired to AD dementia, was analyzed using ELISA, alongside neuropsychological assessments and amyloid PET imaging.

Cocaine polydrug use and its impact on intentional harm recognition: a high-density EEG study.

Background: Cocaine and stimulant consumption constitute a significant global issue and are associated with impaired social skills. However, the relationship between substance abuse and intentional harm recognition remains unclear. Intentional harm recognition is a crucial social cognitive ability that allows individuals to determine whether a harmful action performed by another person is deliberate or accidental.

Connectivity as a universal predictor of tau progression in atypical Alzheimer's disease.

The link between regional tau load and clinical manifestation of Alzheimer's disease (AD) highlights the importance of characterizing spatial tau distribution across disease variants. In typical (memory-predominant) AD, the spatial progression of tau pathology mirrors the functional connections from temporal lobe epicenters. However, given the limited spatial heterogeneity of tau in typical AD, atypical (non-amnestic-predominant) AD variants with distinct tau patterns provide a key opportunity to investigate the universality of connectivity as a scaffold for tau progression.

Association between neuropsychiatric symptoms and neurodegeneration-related plasma biomarkers in older adults with and without clinical dementia in the Democratic Republic of the Congo.

Introduction: Neuropsychiatric symptoms (NPS) are prevalent in dementia, but most studies focus on Western populations. This study examines the association between NPS and neurodegeneration-related plasma biomarkers in older adults with and without dementia in the Democratic Republic of the Congo (DRC).

Methods: Eighty-five individuals (≥65 years) underwent dementia adjudication using the Community Screening Instrument for Dementia (CSID) and Alzheimer's Questionnaire (AQ).

Cognitive Phenotyping of Parkinson's Disease Patients Via Digital Analysis of Spoken Word Properties.

Background: Cognitive symptoms are highly prevalent in Parkinson's disease (PD), often manifesting as mild cognitive impairment (MCI). Yet, their detection and characterization remain suboptimal because standard approaches rely on subjective impressions derived from lengthy, univariate tests.

Objective: We examined whether digital analysis of verbal fluency predicts cognitive status in PD.

White matter hyperintensities and their impact in brain structure and function in alzheimer's disease and behavioral variant frontotemporal dementia across Latin America and the United States: a cross-sectional study.

Background: White matter hyperintensities (WMHs) are a core manifestation of normal and pathological aging and are potentially linked to geographical differences in social and physical exposomes. Previous studies have not examined the impact of WMHs burden on neurodegeneration and cognition in healthy controls (HCs) and patients with Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) across geographic regions. This study addressed this gap by assessing the impact of WMHs burden on participants with and without dementia from Latin America (LA) and the United States (US).

Divergent effects of age on imaging-based ATN biomarkers and cognition in Alzheimer's disease.

Introduction: We investigated whether age of patients with Alzheimer's disease (AD) at first visit to a memory clinic predicts biomarker findings along the amyloid beta deposition, pathologic tau, and neurodegeneration (ATN) scheme and moderates the association between ATN biomarkers and cognition.

Methods: We evaluated [C]Pittsburgh compound B positron emission tomography (PET), florzolotau (F) PET, [F]fluorodeoxyglucose PET, T1-weighted magnetic resonance imaging, and cognitive assessments ( = 190/63/252/687/2198) of a total of 2355 AD patients. We assessed direct and moderating effects of age.

Integrative effects of Telomere Length, Epigenetic Age, and Mitochondrial DNA abundance in Alzheimer's Disease.

Background And Objectives: Biological age, reflecting the cumulative molecular and cellular damage such as telomere attrition, epigenetic alterations and mitochondrial dysfunction, may better capture age-related decline and Alzheimer's disease (AD) risk than chronological age. Most studies have focused on one measure of biological age and not investigated joint or interactive contributions to AD pathogenesis.

Methods: We estimated blood-derived telomere length (TL) via qPCR, epigenetic age (DNAm age) using the CausAge clock, and mitochondrial DNA copy number (mtDNAcn) from whole genome sequencing in 640 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI; Age: 74.

The National Dementia Workforce Study: Methods for Surveying Community Clinicians Who Provide Care to People With Dementia.

People with dementia have complex medical, functional, and social needs and experience highly variable care quality and outcomes across the U.S. health care system.

Early-life Exposure to Punitive School Discipline and Midlife Cognitive Outcomes: 1979 National Longitudinal Survey of Youth Cohort Findings.

Introduction: Suspension and expulsion are common in US schools and disproportionately target structurally marginalized children. No research has examined whether these punitive practices may have long-term cognitive-aging implications.

Methods: In the prospective National Longitudinal Survey of Youth 1979 data (N=8021), we used confounder-adjusted linear models to investigate associations between early-life suspension or expulsion and global cognition, memory, and attention z -scores at age 50.

Psychometric properties of the Dutch version of the social interaction vocabulary task.

Introduction: Social functioning is affected in various ways in behavioral variant frontotemporal dementia (bvFTD), and having tests available to assess aspects of social functioning increases the accuracy of diagnostic evaluation. One such aspect is having an accurate semantic representation of socio-emotional concepts. We designed a clinical test, the social interaction vocabulary task (SIVT), to capture this aspect.

Polygenic Hazard Score for Predicting Age-associated Risk of Alzheimer's Disease in European Populations: Development and Validation.

Objectives: Polygenic hazard score (PHS) models can be used to predict the age-associated risk for complex diseases, including Alzheimer's disease (AD). In this study, we present an improved PHS model for AD that incorporates a large number of genetic variants and demonstrates enhanced predictive accuracy for age of onset in European populations compared to alternative models.

Methods: We used the genotyped European Alzheimer & Dementia Biobank (EADB) sample (n=42,120) to develop and evaluate the performance of the PHS model.

Modernizing diagnosis of Alzheimer's disease: A review of global trends and Asia-specific perspectives.

The landscape of Alzheimer's disease (AD) and related dementias (ADRD) diagnosis is evolving rapidly, driven by advances in disease understanding, biomarker tools, and disease-modifying therapies. Modern diagnostic approaches emphasize biological precision, early detection, and dynamic frameworks that adapt to treatment-induced changes in disease biology. These frameworks enable opportunities for personalized interventions-encompassing pharmacological and non-pharmacological strategies-and for enhanced clinical trial design.

High inter-rater reliability in consensus diagnoses and overall assessment in the Asian Cohort for Alzheimer's Disease Study.

The Asian Cohort for Alzheimer's Disease (ACAD) study is a collaborative investigation of genetic and non-genetic risk factors for AD among Asian Americans and Canadians. Harmonization of diagnostic procedures across recruiting sites will be key to the dataset's efficacy. Forty-two participants who completed the consensus process across seven ACAD recruiting sites were re-reviewed by two further impartial raters.

Multimorbidity in dementia: Current perspectives and future challenges.

Multimorbidity-the co-occurrence of two or more chronic health conditions-affects > 86% of people with dementia. It is associated with cognitive and functional decline, reduced health-related quality of life, increased health-care use, and higher mortality. The relationship between multimorbidity and dementia is potentially bidirectional; conditions such as hypertension and diabetes increase the risk of developing dementia, and cognitive impairment can complicate their management.