Basic Science and Pathogenesis.

Background: We recently found region-specific patterns of iron-rich gliosis in frontotemporal lobar degeneration (FTLD) groups with tau (FTLD-Tau; PSP) and TDP-43 (FTLD-TDP) pathology using iron-sensitive MRI of whole-hemispheres. These patterns largely corresponded to regions of early pathology reported in previous traditional histopathologic staging schemes of protein inclusions for FTLD-Tau and FTLD-TDP. Ferritin light chain (FLC) reactivity highlights activated glia but has not been studied extensively in FTLD.

Posterior hippocampal sparing in Lewy body disorders with Alzheimer's copathology: An in vivo MRI study.

Background: Lewy body disorders (LBD), encompassing Parkinson disease (PD), PD dementia (PDD), and dementia with Lewy bodies (DLB), are characterized by alpha-synuclein pathology but often are accompanied by Alzheimer's disease (AD) neuropathological change (ADNC). The medial temporal lobe (MTL) is a primary locus of tau accumulation and associated neurodegeneration in AD. However, it is unclear the extent to which AD copathology in LBD (LBD/AD+) contributes to MTL-specific patterns of degeneration.

ADNI Biomarker Core: A review of progress since 2004 and future challenges.

Background: We describe the Alzheimer's Disease Neuroimaging Initiative (ADNI) Biomarker Core major activities from October 2004 to March 2024, including biobanking ADNI cerebrospinal fluid (CSF), plasma, and serum biofluid samples, biofluid analyses for Alzheimer's disease (AD) biomarkers in the Biomarker Core and various non-ADNI laboratories, and continuous assessments of pre-analytics.

Results: Validated immunoassay and mass spectrometry-based assays were performed in CSF with a shift to plasma, a more accessible biofluid, as qualified assays became available. Performance comparisons across different CSF and plasma AD biomarker measurement platforms have enriched substantially the ADNI participant database enabling method performance determinations for AD pathology detection and longitudinal assessments of disease progression.

The accuracy of parent/carer proxy-reporting of caries experience in children and association with socioeconomic circumstances: a cross-sectional data linkage study.

Objectives: To compare parent/carer proxy-reported dental caries experience of their 5-year-old child with epidemiological survey clinician examination of caries experience in the same children. To determine any differences in the accuracy by area-based socioeconomic group.

Methods: A cross-sectional data linkage study linked data from the Growing Up in Scotland (GUS) study and the National Dental Inspection Programme (NDIP) school epidemiology survey.

Cytoarchitectonic gradients of laminar degeneration in behavioral variant frontotemporal dementia.

Behavioral variant frontotemporal dementia (bvFTD) is a clinical syndrome primarily caused by either tau (bvFTD-tau) or TDP-43 (bvFTD-TDP) proteinopathies. We previously found lower cortical layers and dorsolateral regions accumulate greater tau than TDP-43 pathology; however, patterns of laminar neurodegeneration across diverse cytoarchitecture in bvFTD is understudied. We hypothesized that bvFTD-tau and bvFTD-TDP have distinct laminar distributions of pyramidal neurodegeneration along cortical gradients, a topologic order of cytoarchitectonic subregions based on increasing pyramidal density and laminar differentiation.

Pathologic and cognitive correlates of plasma biomarkers in neurodegenerative disease.

Introduction: We investigate pathological correlates of plasma phosphorylated tau 181 (p-tau), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) across a clinically diverse spectrum of neurodegenerative disease, including normal cognition (NormCog) and impaired cognition (ImpCog).

Methods: Participants were NormCog (n = 132) and ImpCog (n = 461), with confirmed β-amyloid (Aβ+/-) status (cerebrospinal fluid, positron emission tomography, autopsy) and single molecule array plasma measurements. Logistic regression and receiver operating characteristic (ROC) area under the curve (AUC) tested how combining plasma analytes discriminated Aβ+ from Aβ-.

Automatic classification of AD pathology in FTD phenotypes using natural speech.

Introduction: Screening for Alzheimer's disease neuropathologic change (ADNC) in individuals with atypical presentations is challenging but essential for clinical management. We trained automatic speech-based classifiers to distinguish frontotemporal dementia (FTD) patients with ADNC from those with frontotemporal lobar degeneration (FTLD).

Methods: We trained automatic classifiers with 99 speech features from 1 minute speech samples of 179 participants (ADNC = 36, FTLD = 60, healthy controls [HC] = 89).

Greater white matter degeneration and lower structural connectivity in non-amnestic vs. amnestic Alzheimer's disease.

Introduction: Multimodal evidence indicates Alzheimer's disease (AD) is characterized by early white matter (WM) changes that precede overt cognitive impairment. WM changes have overwhelmingly been investigated in typical, amnestic mild cognitive impairment and AD; fewer studies have addressed WM change in atypical, non-amnestic syndromes. We hypothesized each non-amnestic AD syndrome would exhibit WM differences from amnestic and other non-amnestic syndromes.

Evaluation of ATN Framework and Biofluid Markers to Predict Cognitive Decline in Early Parkinson Disease.

Background And Objectives: In Parkinson disease (PD), Alzheimer disease (AD) copathology is common and clinically relevant. However, the longitudinal progression of AD CSF biomarkers-β-amyloid 1-42 (Aβ), phosphorylated tau 181 (p-tau), and total tau (t-tau)-in PD is poorly understood and may be distinct from clinical AD. Moreover, it is unclear whether CSF p-tau and serum neurofilament light (NfL) have added prognostic utility in PD, when combined with CSF Aβ.

Tau maturation in the clinicopathological spectrum of Lewy body and Alzheimer's disease.

Objective: Alzheimer's disease neuropathologic change and alpha-synucleinopathy commonly co-exist and contribute to the clinical heterogeneity of dementia. Here, we examined tau epitopes marking various stages of tangle maturation to test the hypotheses that tau maturation is more strongly associated with beta-amyloid compared to alpha-synuclein, and within the context of mixed pathology, mature tau is linked to Alzheimer's disease clinical phenotype and negatively associated with Lewy body dementia.

Methods: We used digital histology to measure percent area-occupied by pathology in cortical regions among individuals with pure Alzheimer's disease neuropathologic change, pure alpha-synucleinopathy, and a co-pathology group with both Alzheimer's and alpha-synuclein pathologic diagnoses.

Changes in Digital Speech Measures in Asymptomatic Carriers of Pathogenic Variants Associated With Frontotemporal Degeneration.

Background And Objectives: Clinical trials developing therapeutics for frontotemporal degeneration (FTD) focus on pathogenic variant carriers at preclinical stages. Objective, quantitative clinical assessment tools are needed to track stability and delayed disease onset. Natural speech can serve as an accessible, cost-effective assessment tool.

Comparison of category and letter fluency tasks through automated analysis.

Introduction: Category and letter fluency tasks are commonly used neuropsychological tasks to evaluate lexical retrieval.

Methods: This study used validated automated methods, which allow for more expansive investigation, to analyze speech production of both category ("Animal") and letter ("F") fluency tasks produced by healthy participants ( = 36) on an online platform. Recordings were transcribed and analyzed through automated pipelines, which utilized natural language processing and automatic acoustic processing tools.

Alzheimer Disease Biomarkers: Moving from CSF to Plasma for Reliable Detection of Amyloid and tau Pathology.

Background: Development of validated biomarkers to detect early Alzheimer disease (AD) neuropathology is needed for therapeutic AD trials. Abnormal concentrations of "core" AD biomarkers, cerebrospinal fluid (CSF) amyloid beta1-42, total tau, and phosphorylated tau correlate well with neuroimaging biomarkers and autopsy findings. Nevertheless, given the limitations of established CSF and neuroimaging biomarkers, accelerated development of blood-based AD biomarkers is underway.

The lived experience of reconstructing identity in response to genetic risk of frontotemporal degeneration and amyotrophic lateral sclerosis.

With the increasing availability of predictive genetic testing for adult-onset neurodegenerative conditions, it is imperative that we better understand the impact of learning one's risk status. Frontotemporal degeneration (FTD) is the second most prevalent cause of early-onset dementia. About one-third of patients have an identifiable genetic etiology, and some genetic variants that cause FTD can also cause amyotrophic lateral sclerosis (ALS).

Building resilient hospital information technology services through organizational learning: Lessons in CIO leadership during an international systemic crisis in the United States and Abu Dhabi, United Arab Emirates.

Background: The COVID-19 pandemic was an international systemic crisis which required an unprecedented response to quickly drive the digital transformation of hospitals and health care systems to support high quality health care while adhering to contagion management protocols.

Objective: To identify and assess the best practices during the COVID-19 pandemic by Chief Information Officers (CIOs) about how to build resilient healthcare IT (HIT) to improve pandemic preparedness and response across global settings and to develop recommendations for future pandemics.

Methods: We conducted a qualitative, interview-based study to sample CIOs in hospitals.

The role of oxylipins in NSAID-exacerbated respiratory disease (N-ERD).

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is characterized by nasal polyp formation, adult-onset asthma, and hypersensitivity to all cyclooxygenase-1 (COX-1) inhibitors. Oxygenated lipids are collectively known as oxylipins and are polyunsaturated fatty acids (PUFA) oxidation products. The most extensively researched oxylipins being the eicosanoids formed from arachidonic acid (AA).

Evaluation of an educational conference for persons affected by hereditary frontotemporal degeneration and amyotrophic lateral sclerosis.

Objective: There are limited studies exploring the support and education needs of individuals at-risk for or diagnosed with hereditary frontotemporal degeneration (FTD) and/or amyotrophic lateral sclerosis (ALS). This study evaluated a novel conference for this population to assess conference efficacy, probe how participants assessed relevant resources, and identify outstanding needs of persons at-risk/diagnosed.

Methods: We implemented a post-conference electronic survey that probed participants' satisfaction, prior experience with resources, and unmet needs.

Detection of SARS-CoV-2 Antibodies in Immunoglobulin Products.

Background: For patients with primary antibody deficiency, the first line of therapy is replacement with immunoglobulin (Ig) products. Prior to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, Ig products did not contain antibodies with specificity for this virus, and there have been limited data on the antibodies present in the Ig products in current use.

Objective: To quantitatively examine SARS-CoV-2 antibodies in current Ig products.

Plasma GFAP associates with secondary Alzheimer's pathology in Lewy body disease.

Objective: Within Lewy body spectrum disorders (LBSD) with α-synuclein pathology (αSyn), concomitant Alzheimer's disease (AD) pathology is common and is predictive of clinical outcomes, including cognitive impairment and decline. Plasma phosphorylated tau 181 (p-tau ) is sensitive to AD neuropathologic change (ADNC) in clinical AD, and plasma glial fibrillary acidic protein (GFAP) is associated with the presence of β-amyloid plaques. While these plasma biomarkers are well tested in clinical and pathological AD, their diagnostic and prognostic performance for concomitant AD in LBSD is unknown.