Distinct spatiotemporal atrophy patterns in corticobasal syndrome are associated with different underlying pathologies.

Although the corticobasal syndrome was originally most closely linked with the pathology of corticobasal degeneration, the 2013 Armstrong clinical diagnostic criteria, without the addition of aetiology-specific biomarkers, have limited positive predictive value for identifying corticobasal degeneration pathology in life. Autopsy studies demonstrate considerable pathological heterogeneity in corticobasal syndrome, with corticobasal degeneration pathology accounting for only ∼50% of clinically diagnosed individuals. Individualized disease stage and progression modelling of brain changes in corticobasal syndrome may have utility in predicting this underlying pathological heterogeneity, and in turn improve the design of clinical trials for emerging disease-modifying therapies.

Clinical and Imaging Features of Sporadic and Genetic Frontotemporal Lobar Degeneration TDP-43 A and B.

Objective: Certain frontotemporal lobar degeneration subtypes, including TDP-A and B, can either occur sporadically or in association with specific genetic mutations. It is uncertain whether syndromic or imaging features previously associated with these patient groups are subtype or genotype specific. Our study sought to discern the similarities and differences between sporadic and genetic TDP-A and TDP-B.

Copy Number Variation and Haplotype Analysis of 17q21.31 Reveals Increased Risk Associated with Progressive Supranuclear Palsy and Gene Expression Changes in Neuronal Cells.

Background: The 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents the strongest risk locus in progressive supranuclear palsy (PSP).

Objective: To investigate the association between CNVs and structural forms on 17q.

Imaging Synaptic Density in Aging and Alzheimer Disease with [F]SynVesT-1.

Synaptic density imaging with PET is a relatively new approach to monitoring synaptic injury in neurodegenerative diseases. However, there are remaining technical and clinical questions, including questions on reference region selection and on how specific phenotypic presentations and symptoms of Alzheimer disease (AD) are reflected in alterations in synaptic density. Using a synaptic vesicle glycoprotein 2A (SV2A) PET ligand radiolabeled with the F isotope ([F]SynVesT-1), we performed sensitivity analyses to determine the optimal reference tissue modeling approach to derive whole-brain ratio images.

The interplay between age at menopause and synaptic integrity on Alzheimer's disease risk in women.

Menopause is a major biological transition that may influence women's late-life brain health. Earlier estrogen depletion-via earlier menopause-has been associated with increased risk for Alzheimer's disease (AD). Synaptic dysfunction also incites and exacerbates AD progression.

Aging activates escape of the silent X chromosome in the female mouse hippocampus.

Women live longer than men and exhibit less cognitive aging. The X chromosome contributes to sex differences, as females harbor an inactive X (Xi) and active X (Xa), in contrast to males with only an Xa. Thus, reactivation of silent Xi genes may contribute to sex differences.

Semantic variant primary progressive aphasia with ANXA11 p.D40G.

Introduction: Pathogenic variants of annexin A11 (ANXA11) have been identified in patients with amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD). We explored ANXA11 pathogenic variants in a Korean FTD cohort to investigate the prevalence and the role of ANXA11 variation in FTD.

Methods: We used next-generation sequencing (NGS) to search for pathogenic variants in ANXA11 in two nationwide FTD cohorts in Korea.

Considerations in the clinical use of amyloid PET and CSF biomarkers for Alzheimer's disease.

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 research settings to determine Aβ status, biomarker testing in clinical practice requires careful consideration of the strengths and limitations of each modality, as well as the specific clinical context, to identify which test is best suited for each patient. This article provides a comprehensive review of the pathologic processes reflected by Aβ-PET and CSF biomarkers, their performance, and their current and future applications and contexts of use.

Perceptions About Housing and Neighborhood Characteristics Among Aging Adult Black Americans in Two Predominantly Black, Low-Income Neighborhoods in Pittsburgh: A Multi-Method Analysis.

The life expectancy gap between Black and White Americans has narrowed, but progress remains slow due to the persistent consequences of lifetime exposure to structural and interpersonal experiences of racism and discrimination in various settings, for example, disadvantaged housing, neighborhood, and economic conditions. It is important to understand challenges and facilitators to healthy aging among Black Americans, i.e.

2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy.

Valosin-containing protein (VCP/p97) is a ubiquitously expressed AAA+ ATPase associated with numerous protein-protein interactions and critical cellular functions including protein degradation and clearance, mitochondrial homeostasis, DNA repair and replication, cell cycle regulation, endoplasmic reticulum-associated degradation, and lysosomal functions including autophagy and apoptosis. Autosomal-dominant missense mutations in the VCP gene may result in VCP-associated multisystem proteinopathy (VCP-MSP), a rare degenerative disorder linked to heterogeneous phenotypes including inclusion body myopathy (IBM) with Paget's disease of bone (PDB) and frontotemporal dementia (FTD) or IBMPFD, amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), parkinsonism, Charcot-Marie Tooth disease (CMT), and spastic paraplegia. The complexity of VCP-MSP makes collaboration among stakeholders essential and necessitates a multi-disciplinary approach.

Navigating barriers to dementia specialty care among vulnerable populations: Insight from a multidiscipline care navigation team.

The emergency department evaluates many patients with undiagnosed cognitive impairment and presents an opportune setting to facilitate early detection and referral to memory care specialists. We evaluated a novel care navigation pathway that facilitated referrals of ethnoculturally diverse individuals with suspected cognitive impairment from geriatric professionals embedded in the emergency department to dementia specialist care. We compared rates of referrals and successful appointment attendance for patients in this pathway compared to patients in a traditional primary care provider referral pathway.

Validation of the Cognitive-Emotional Perspective Taking test in patients with neurodegeneration.

BackgroundTheory of mind (ToM) is crucial for socioemotional interaction. ToM deficits may explain behavioral changes in dementia, especially Alzheimer's disease (AD) and frontotemporal dementia (FTD).ObjectiveThis study examined the psychometrics of a new ToM test in healthy adults, identified ToM differences in dementia syndromes, and assessed if ToM scores predict neuropsychiatric function and real-life behavior.

Exploring cognitive and neuroimaging profiles of dementia subtypes of individuals with dementia in the Democratic Republic of Congo.

Objective: The 2024 Alzheimer's Association (AA) research diagnostic criteria for Alzheimer's Disease (AD) considers fluid biomarkers, including promising blood-based biomarkers for detecting AD. This study aims to identify dementia subtypes and their cognitive and neuroimaging profiles in older adults with dementia in the Democratic Republic of Congo (DRC) using biomarkers and clinical data.

Methods: Forty-five individuals with dementia over 65 years old were evaluated using the Community Screening Instrument for Dementia and the informant-based Alzheimer's Questionnaire.

Methods to crosswalk between cognitive test scores using data from the Alzheimer's Disease Neuroimaging Cohort.

Introduction: Studies use multiple different instruments to measure dementia-related outcomes, making head-to-head comparisons of interventions difficult.

Methods: To address this gap, we developed two methods to crosswalk estimated treatment effects on cognitive outcomes that are flexible, broadly applicable, and do not rely on strong distributional assumptions.

Results: We present two methods to crosswalk effect estimates using one measure to estimates using another measure, illustrated with global cognitive measures from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Exposure to autoimmune disorders is associated with increased Alzheimer's disease risk in a multi-site electronic health record analysis.

Autoimmunity has been proposed to increase Alzheimer's disease (AD) risk, but evaluating the clinical connection between autoimmune disorders and AD has been difficult in diverse populations. We investigate risk relationships between 26 autoimmune disorders and AD using retrospective observational case-control and cohort study designs based on electronic health records for >300,000 individuals at the University of California, San Francisco (UCSF) and Stanford University. We discover that autoimmune disorders are associated with increased AD risk (odds ratios [ORs] 1.

F-MK-6240 tau PET in patients at-risk for chronic traumatic encephalopathy.

Background: Molecular biomarkers of chronic traumatic encephalopathy (CTE) are lacking. We evaluated F-MK-6240 tau PET as a biomarker for CTE. Two studies were done: (1) H-MK-6240 autoradiography and an in-vitro brain homogenate binding studies on postmortem CTE tissue, (2) an in-vivo F-MK-6240 tau PET study in former American football players.

Machine learning prediction of tau-PET in Alzheimer's disease using plasma, MRI, and clinical data.

Introduction: Tau positron emission tomography (PET) is a reliable neuroimaging technique for assessing regional load of tau pathology in the brain, but its routine clinical use is limited by cost and accessibility barriers.

Methods: We thoroughly investigated the ability of various machine learning models to predict clinically useful tau-PET composites (load and laterality index) from low-cost and non-invasive features, for example, clinical variables, plasma biomarkers, and structural magnetic resonance imaging (MRI).

Results: Models including plasma biomarkers yielded the most accurate predictions of tau-PET burden (best model: R-squared = 0.

Role of tau versus TDP-43 pathology on medial temporal lobe atrophy in aging and Alzheimer's disease.

Hippocampal atrophy on magnetic resonance imaging is an important biomarker in Alzheimer's disease (AD). While hippocampal atrophy was thought to result from tau tangles in AD, different neuropathologies can lead to hippocampal atrophy, especially TAR DNA-binding protein 43 (TDP-43) pathology. In this narrative review, we evaluate existing studies on the relative contribution of tau and TDP-43 pathology to medial temporal lobe (MTL) atrophy.

A semantic strength and neural correlates in developmental dyslexia.

Introduction: Most studies of dyslexia focus on domains of impairment (e.g., reading and phonology, among others), but few examine possible strengths.

Identifying pathways to the prevention of dementia: the Netherlands consortium of dementia cohorts.

Background: Aggregation of cohort data increases precision for studying neurodegenerative disease pathways, but efforts to combine data and expertise are often hampered by infrastructural, ethical and legal considerations. We aimed to unite various cohort studies in the Netherlands to enhance research infrastructure and facilitate research on dementia etiology and its public health implications.

Methods: The Netherlands Consortium of Dementia Cohorts (NCDC) includes participants with initially no established cognitive impairment from 9 Dutch cohorts: the Amsterdam Dementia Cohort (ADC), Doetinchem Cohort Study (DCS), European Medical Information Framework for Alzheimer's Disease (EMIF-AD), Longitudinal Aging Study Amsterdam (LASA), the Leiden Longevity Study (LLS), The Maastricht Study, the Memolife substudy of the Lifelines cohort, Rotterdam Study and Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study.

Detection of Alzheimer Neuropathology in Alzheimer and Non-Alzheimer Clinical Syndromes With Blood-Based Biomarkers.

Importance: Blood-based biomarkers for Alzheimer disease (AD) are clinically available, but their value is not well understood in syndromes typically associated with frontotemporal lobar degeneration syndromes (FTLD).

Objective: To investigate the clinical importance and detectability of AD in FTLD-related neurodegenerative syndromes using 3 plasma biomarkers, phosphorylated tau 217 (p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP).

Design, Setting, And Participants: This clinicopathological study took place at the University of California San Francisco Alzheimer Disease Research Center from August 2008 to July 2022.

Reduced levels of angiogenesis biomarkers predict increased symptom severity in Chinese Americans with Alzheimer's disease with demographic-specific effect.

Alzheimer's disease (AD) symptomatology, while classically studied through the lens of amyloid-β and tau burden, is likely also influenced by multiple-interacting co-pathologies like vascular disease and dysmetabolism. These co-pathologies, especially vascular disease, occur disparately in the Chinese-American population and are often treatable via therapeutics and lifestyle modifications. Given this, we explored whether plasma biomarkers, including an array of vascular-related proteins, associate with cognition in a cohort of 34 Chinese Americans clinically diagnosed as cognitively normal, with mild cognitive impairment, or with AD.

"By the Time We Knew …": Poetic Analysis of End-of-Life Caregiving Experiences for Rapidly Progressive and Slower-Duration Dementia Syndromes.

Background: One in three older adults in the United States dies with or from dementia. Little is known about whether end-of-life caregiving experiences differ by dementia diagnosis.

Methods: We conducted a secondary analysis of two qualitative studies.

Elevated vascular endothelial growth factor a is associated with disruption of default network connectivity in older adults.

Vascular Endothelial Growth Factor A (VEGF-A) is an angiogenic signaling protein involved in the maintenance of the cerebral vasculature. No prior study has explored whether plasma VEGF-A levels may be associated with brain functional connectivity changes, such as disruption of the default mode network (DMN), which often precedes the development of cognitive changes in aging. Seventy-six independently living older adults (mean age = 70.