Longitudinal clinical, cognitive and biomarker profiles in dominantly inherited versus sporadic early-onset Alzheimer's disease.

Approximately 5% of Alzheimer's disease cases have an early age at onset (<65 years), with 5-10% of these cases attributed to dominantly inherited mutations and the remainder considered as sporadic. The extent to which dominantly inherited and sporadic early-onset Alzheimer's disease overlap is unknown. In this study, we explored the clinical, cognitive and biomarker profiles of early-onset Alzheimer's disease, focusing on commonalities and distinctions between dominantly inherited and sporadic cases.

Association of Systemic Lupus Erythematosus Disease Activity With Choroidal Thickness.

Objective: To determine the association between disease activity and choroidal thickness in patients with systemic lupus erythematosus (SLE).

Methods: We conducted a cohort study of 24 SLE patients and 13 healthy controls recruited at Washington University School of Medicine between June 2019 and November 2021. SLE disease activity was assessed using the SLE Disease Activity Index-2000 Responder Index-50 (S2K RI-50).

Retention of Study Partners in Longitudinal Studies of Alzheimer Disease.

Background: Study partners are required for all participants at Alzheimer's Disease Research Centers (ADRCs). Study partners' attitudes and beliefs may contribute to missed visits and negatively impact retention of participants in longitudinal AD studies.

Objective: Study partners (N = 212) of participants (Clinical Dementia Rating® [CDR]≤2) at four ADRCs were randomly surveyed to examine their facilitators and barriers to continued participation in AD studies.

Assessing deviations for HPCs obtained during COVID-19 (ADHOC): Evaluating impact of the COVID-19 pandemic on cellular therapy products and processes, the BEST collaborative study.

Background: The success of allogeneic hematopoietic stem cell transplantation is dependent on a world-wide network of collection centers providing donations that predominantly have been infused as fresh cells. The logistics chain that supports the just-in-time delivery model for stem cell and immunotherapy products was severely stressed by the COVID pandemic, and in early 2020 a number of national and international bodies recommended that cells should be cryopreserved at the collection or transplant center to avoid interruptions in their acquisition or delivery to patients who had started conditioning.

Study Design: To assess the potential consequences of such pandemic-related deviations to normal practice, we surveyed nine international laboratories to determine if the characteristics or transplant outcomes of allogeneic stem cell donations differed in the immediate periods before and after the switch to routine cryopreservation.

Cross-sectional and longitudinal comparisons of biomarkers and cognition among asymptomatic middle-aged individuals with a parental history of either autosomal dominant or late-onset Alzheimer's disease.

Background: Comparisons of late-onset Alzheimer's disease (LOAD) and autosomal dominant AD (ADAD) are confounded by age.

Methods: We compared biomarkers from cerebrospinal fluid (CSF), magnetic resonance imaging, and amyloid imaging with Pittsburgh Compound-B (PiB) across four groups of 387 cognitively normal participants, 42 to 65 years of age, in the Dominantly Inherited Alzheimer Network (DIAN) and the Adult Children Study (ACS) of LOAD: DIAN mutation carriers (MCs) and non-carriers (NON-MCs), and ACS participants with a positive (FH+) and negative (FH-) family history of LOAD.

Results: At baseline, MCs had the lowest age-adjusted level of CSF Aβ42 and the highest levels of total and phosphorylated tau-181, and PiB uptake.

Preclinical Alzheimer's disease biomarkers accurately predict cognitive and neuropathological outcomes.

Alzheimer's disease biomarkers are widely accepted as surrogate markers of underlying neuropathological changes. However, few studies have evaluated whether preclinical Alzheimer's disease biomarkers predict Alzheimer's neuropathology at autopsy. We sought to determine whether amyloid PET imaging or CSF biomarkers accurately predict cognitive outcomes and Alzheimer's disease neuropathological findings.

Perceptions of Research Burden and Retention Among Participants in ADRC Cohorts.

Objectives: Alzheimer disease (AD) and related dementias clinical research is associated with significant participant burden. The Perceived Research Burden Assessment (PeRBA) measures participants' perceptions of logistical, psychological, and physical burdens. The purpose of this study was to assess PeRBA's psychometric properties, perceptual sources, and behavioral consequences with participants in a multisite study of participant retention in longitudinal cohort studies of Alzheimer disease and related dementias.

Autosomal dominant and sporadic late onset Alzheimer's disease share a common in vivo pathophysiology.

The extent to which the pathophysiology of autosomal dominant Alzheimer's disease corresponds to the pathophysiology of 'sporadic' late onset Alzheimer's disease is unknown, thus limiting the extrapolation of study findings and clinical trial results in autosomal dominant Alzheimer's disease to late onset Alzheimer's disease. We compared brain MRI and amyloid PET data, as well as CSF concentrations of amyloid-β42, amyloid-β40, tau and tau phosphorylated at position 181, in 292 carriers of pathogenic variants for Alzheimer's disease from the Dominantly Inherited Alzheimer Network, with corresponding data from 559 participants from the Alzheimer's Disease Neuroimaging Initiative. Imaging data and CSF samples were reprocessed as appropriate to guarantee uniform pipelines and assays.

Retaining Participants in Longitudinal Studies of Alzheimer's Disease.

Background: Retention of study participants is essential to advancing Alzheimer's disease (AD) research and developing therapeutic interventions. However, recent multi-year AD studies have lost 10% to 54% of participants.

Objective: We surveyed a random sample of 443 participants (Clinical Dementia Rating [CDR]≤1) at four Alzheimer Disease Research Centers to elucidate perceived facilitators and barriers to continued participation in longitudinal AD research.

IL-33 signaling in sensory neurons promotes dry skin itch.

Background: Chronic pruritus, or itch, is common and debilitating, but the neuroimmune mechanisms that drive chronic itch are only starting to be elucidated. Recent studies demonstrate that the IL-33 receptor (IL-33R) is expressed by sensory neurons. However, whether sensory neuron-restricted activity of IL-33 is necessary for chronic itch remains poorly understood.

Predicting Symptom Onset in Sporadic Alzheimer Disease With Amyloid PET.

Background And Objectives: To predict when cognitively normal individuals with brain amyloidosis will develop symptoms of Alzheimer disease (AD).

Methods: Brain amyloid burden was measured by amyloid PET with Pittsburgh compound B. The mean cortical standardized uptake value ratio (SUVR) was transformed into a timescale with the use of longitudinal data.

Inclusion of Thyroid Nodule Location in American College of Radiology TI-RADS Scoring: Impact on System Performance.

Emerging data suggest that the location of thyroid nodules influences malignancy risk. The purpose of this study was to explore the impact of including location in American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) scoring. Four of five revised scoring algorithms that added 1 or 2 points to higher-risk locations were associated with lowered accuracy due to lower specificity.

Ante- and postmortem tau in autosomal dominant and late-onset Alzheimer's disease.

Antemortem tau positron emission tomography imaging suggests elevated tau pathology in autosomal dominant versus late-onset Alzheimer's disease at equivalent clinical stages, but does not implicate the specific tau pathologies responsible. Here we made stereological measurements of tau neurofibrillary tangles, neuritic plaques, and neuropil threads and found compared to late-onset Alzheimer's disease, autosomal dominant Alzheimer's disease showed even greater tangle and thread burdens. Regional tau burden resembled that observed in tau imaging of a separate cohort at earlier clinical stages.

Socioeconomic Status Mediates Racial Differences Seen Using the AT(N) Framework.

Objectives: African Americans are at greater risk for developing Alzheimer's disease (AD) dementia than non-Hispanic whites. In addition to biological considerations (eg, genetic influences and comorbid disorders), social and environmental factors may increase the risk of AD dementia. This paper (1) assesses neuroimaging biomarkers of amyloid (A), tau (T), and neurodegeneration (N) for potential racial differences and (2) considers mediating effects of socioeconomic status (SES) and measures of small vessel and cardiovascular disease on observed race differences.

Complex interactions underlie racial disparity in the risk of developing Alzheimer's disease dementia.

Introduction: We aim to determine racial disparities and their modifying factors in risk for Alzheimer's disease (AD) dementia among cognitively normal individuals 65 years or older.

Methods: Longitudinal data from the National Alzheimer's Coordinating Center Uniform Data Set on 1229 African Americans (AAs) and 6679 whites were analyzed for the risk of AD using competing risk models with death as a competing event.

Results: Major AD risk factors modified racial differences which, when statistically significant, occurred only with older age among APOE ε4 negative individuals, but also with younger age among APOE ε4 positive individuals.

Comparative Performance and Neuropathologic Validation of the AD8 Dementia Screening Instrument.

Background/objective: The AD8 informant-based screening instrument has been validated with molecular biomarkers of Alzheimer disease (AD) but not with the gold standard of neuropathologic AD. The objective of this study was to validate the AD8 with neuropathologic AD and compare its predictive performance with that of the Mini-Mental State Examination and both participant-derived and informant-derived subjective memory complaint (SMC) regarding the participant.

Methods: This longitudinal cohort study at the Knight Alzheimer Disease Research Center at Washington University included 230 participants, ages 50 to 91 years, who later had a neuropathologic examination.

Association of Acquired and Heritable Factors With Intergenerational Differences in Age at Symptomatic Onset of Alzheimer Disease Between Offspring and Parents With Dementia.

Importance: Acquired and heritable traits are associated with dementia risk; however, how these traits are associated with age at symptomatic onset (AAO) of Alzheimer disease (AD) is unknown. Identifying the associations of acquired and heritable factors with variability in intergenerational AAO of AD could facilitate diagnosis, assessment, and counseling of the offspring of parents with AD.

Objective: To quantify the associations of acquired and heritable factors with intergenerational differences in AAO of AD.

Dural lymphatics regulate clearance of extracellular tau from the CNS.

Background: Alzheimer's disease is characterized by two main neuropathological hallmarks: extracellular plaques of amyloid-β (Aβ) protein and intracellular aggregates of tau protein. Although tau is normally a soluble monomer that bind microtubules, in disease it forms insoluble, hyperphosphorylated aggregates in the cell body. Aside from its role in AD, tau is also involved in several other neurodegenerative disorders collectively called tauopathies, such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), some forms of frontotemporal dementia, and argyrophilic grain disease (AGD).

Staging biomarkers in preclinical autosomal dominant Alzheimer's disease by estimated years to symptom onset.

Introduction: Staging preclinical Alzheimer disease (AD) by the expected years to symptom onset (EYO) in autosomal dominant AD (ADAD) through biomarker correlations is important.

Methods: We estimated the correlation matrix between EYO/cognition and imaging/CSF biomarkers, and searched for the EYO cutoff where a change in the correlations occurred before and after the cutoff among the asymptomatic mutation carriers of ADAD. We then estimated the longitudinal rate of change for biomarkers/cognition within each preclinical stage defined by the EYO.

Effect of apolipoprotein E4 on clinical, neuroimaging, and biomarker measures in noncarrier participants in the Dominantly Inherited Alzheimer Network.

The apolipoprotein E ε4 allele (APOE4) is the major genetic risk factor for sporadic Alzheimer's disease (AD). APOE4 may have effects on cognition and brain atrophy years before the onset of symptomatic AD. We analyzed the effects of APOE4 in a unique cohort of young adults who had undergone comprehensive assessments as part of the Dominantly Inherited Alzheimer Network (DIAN), an international longitudinal study of individuals from families with autosomal dominant AD.

Examining the Complicated Relationship Between Depressive Symptoms and Cognitive Impairment in Preclinical Alzheimer Disease.

Introduction: The relationships between Alzheimer disease (AD), cognitive performance, and depression are poorly understood. It is unclear whether depressive features are a prodrome of AD. In addition, some studies of aging exclude depressed individuals, which may inappropriately limit generalizability.

Association of Preclinical Alzheimer Disease With Optical Coherence Tomographic Angiography Findings.

Importance: Biomarker testing for asymptomatic, preclinical Alzheimer disease (AD) is invasive and expensive. Optical coherence tomographic angiography (OCTA) is a noninvasive technique that allows analysis of retinal and microvascular anatomy, which is altered in early-stage AD.

Objective: To determine whether OCTA can detect early retinal alterations in cognitively normal study participants with preclinical AD diagnosed by criterion standard biomarker testing.

Prevalence, management, and outcome of problem residents among neurosurgical training programs in the United States.

OBJECTIVE: The challenging nature of neurosurgical residency necessitates that appropriate measures are taken by training programs to ensure that residents are properly progressing through their education. Residents who display a pattern of performance deficiencies must be identified and promptly addressed by faculty and program directors to ensure that resident training and patient care are not affected. While studies have been conducted to characterize these so-called "problem residents" in other specialties, no current data regarding the prevalence and management of such residents in neurosurgery exist.

A survival model for unthinned loblolly pine plantations that incorporates non-planted tree competition, site quality, and incidence of fusiform rust.

Future biomass yields are functionally related to the number of trees surviving at a given age. A stand level survival model was developed that incorporates competition of non-planted trees, site quality, and the incidence of fusiform rust (Cronartium quercuum [Berk.] Miyabe ex Shirai f.