The Pelvic Floor Disorders Network: Evolution Over Two Decades of Female Pelvic Floor Research.

Importance: This review aimed to describe research initiatives, evolution, and processes of the Eunice Kennedy Shriver National Institute of Child Health and Human Development-supported Pelvic Floor Disorders Network (PFDN). This may be of interest and inform researchers wishing to conduct multisite coordinated research initiatives as well as to provide perspective to all urogynecologists regarding how the PFDN has evolved and functions.

Study Design: Principal investigators of several PFDN clinical sites and Data Coordinating Center describe more than 20 years of development and maturation of the PFDN.

Prediction of Retention Indices in LC-HRMS for Enhanced Structural Identification of Organic Micropollutants in Water: Selectivity-Based Filtration.

Addressing the global challenge of ensuring access to safe drinking water, especially in developing countries, demands cost-effective, eco-friendly, and readily available technologies. The persistence, toxicity, and bioaccumulation potential of organic pollutants arising from various human activities pose substantial hurdles. While high-performance liquid chromatography coupled with high-resolution mass spectrometry (HPLC-HRMS) is a widely utilized technique for identifying pollutants in water, the multitude of structures for a single elemental composition complicates structural identification.

Nicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway.

Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited.

Basic Science and Pathogenesis.

Background: Neuropsychiatric Symptoms (NPS) including aggression, psychosis, anxiety, apathy and depression are highly prevalent in Alzheimer's Disease patients and are associated with accelerated decline and a detrimental impact on suffering and quality of life of both patients and caregivers. There are no effective pharmaceutical interventions targeting these symptoms, making a better understanding of the etiologic mechanisms underlying NPS in AD critical to develop improved treatments.

Method: To facilitate identification of genetic loci and mechanistic pathways underlying NPS in AD, we have initiated an effort (NIH: U01AG079850) to collate and harmonize all available NPS data in over 70 cohorts (>80,000 samples) of diverse ancestries with whole-genome sequencing data from the Alzheimer's Disease Sequencing Project (ADSP), and analyze these data to identify genetic loci and mechanistic pathways associated with NPS in AD.

Basic Science and Pathogenesis.

Background: Currently, it is unclear to what extent late-onset Alzheimer's disease (AD) risk variants contribute to early-onset AD (EOAD). One method to clarify the contribution of late-onset AD genetic risk to EOAD is to investigate the association of AD polygenic risk scores (PRS) with EOAD. We hypothesize that in the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS), EOAD participants will have greater PRS than early-onset amyloid-negative cognitively-impaired participants (EOnonAD) and controls, and investigate the association of AD PRS with age of disease onset (AoO) and cognitive performance.

Basic Science and Pathogenesis.

Background: Chitinase-3-like protein 1 (CHI3L1, or YKL-40) is an important regulator of immunity and, in the brain, is primarily secreted by activated astrocytes and heralds a neurotoxic inflammatory state. While it has been well known as a high-profile biomarker for Alzheimer's disease (AD) and inflammatory brain conditions (e.g.

Basic Science and Pathogenesis.

Background: TBI is the 3rd greatest risk factor for developing AD, behind genetics and aging. TBI is associated with a 3-4 year earlier onset of cognitive impairment, and increased cortical thinning and amyloid plaques in people with AD. The underlying mechanisms of this relationship are not understood, and as a result there are no treatments that protect patients from accelerated AD after TBI.

Tissue-resident NK cells do their own glandscaping.

In this issue of JEM, Sparano et al. (https://doi.org/10.

Basic Science and Pathogenesis.

Background: Autosomal dominant progranulin (GRN) mutations are a common genetic cause of frontotemporal lobar degeneration. Though clinical trials for GRN-related therapies are underway, there is an unmet need for biomarkers that can predict symptom onset and track disease progression. We previously showed that presymptomatic GRN carriers exhibit thalamocortical hyperconnectivity that increases with age when they are presumably closer to symptom onset.

Basic Science and Pathogenesis.

ARIA-E/H (amyloid-related imaging abnormalities-Edema/Hemorrhage) is an umbrella term that defines the radiographic appearance of MRI images abnormality during treatments with Aβ-lowering monoclonal antibodies (mAbs) for Alzheimer's disease immunotherapy. Today, it is well-recognized that ARIA-E events can also occur spontaneously in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri), a rare autoimmune encephalopathy associated with raised cerebrospinal fluid (CSF) concentrations of spontaneous auto-antibodies against Aβ (aAbs). In this framework, the last years of research and experience of the iCAB international Network generated an increased consensus that therapy-induced ARIA is the iatrogenic manifestation of CAA-ri.

Basic Science and Pathogenesis.

Background: The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is analyzing the genetic etiology of early onset (40-64 years) cognitive impairment, including amyloid-positive early-onset Alzheimer's disease (EOAD) and amyloid-negative early-onset Alzheimer's disease (EOnonAD). One goal of this investigation is to identify novel or under-characterized genetic variants.

Methods: Cognitively impaired (CI) LEADS participants, including amyloid-positive and amyloid-negative early-onset cases, were whole exome or genome sequenced (N = 361).

Clinical Manifestations.

Background: Frontotemporal dementia (FTD) presents with heterogeneous neuropsychiatric symptoms (NPS). These symptoms often begin prior to the onset of FTD, and progress throughout the prodromal stages of FTD. Particularly, familial FTD due to autosomal dominant genetic mutations might display mutation-specific NPS profiles.

Clinical Manifestations.

Background: It has been shown that dysbiosis, or dysfunction of the gastrointestinal (gut) microbiome is associated with Alzheimer's disease (AD). Here, we aimed to expand on beyond our previously reported findings of the gut microbiome associating with AD and explore if the gut microbiome is predictive of cognitive performance in individuals with AD. We sought to identity what cognitive domains are associated with the microbiome in our cohort of AD patients and healthy controls without dementia.

Clinical Manifestations.

Background: Widespread cognitive impairments have previously been documented in Early-Onset Alzheimer's Disease (EOAD) relative to cognitively normal (CN) same-aged peers or those with cognitive impairment without amyloid pathology (Early-Onset non-Alzheimer's Disease; EOnonAD; Hammers et al., 2023). Prior preliminary work has similarly observed worse cognitive performance being associated with earlier ages in EOAD participants enrolled in the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS; Apostolova et al.

Clinical Manifestations.

Background: Traditional cognitive and daily functioning measures that utilize episodic assessment schedules are less sensitive to subtle within-person change in those at risk for Alzheimer's disease (AD). This study aimed to evaluate whether longitudinal trajectories of high frequency cognitive assessments (HFA) and passively assessed higher order instrumental activities of daily living (IADLs) differ between those with intact cognition (CN, n = 59) and mild cognitive impairment (MCI, n = 45). An exploratory aim evaluated whether the use of person-specific distributions would detect differences in longitudinal trajectories not captured by traditional between-group analyses.

Clinical Manifestations.

Background: Recent studies showed that neuroinflammation plays a key role in triggering specific neuropsychiatric symptoms (NPS), such as irritability and agitation, in individuals with Alzheimer's disease (AD). While prior studies showed an association between tau pathology and all NPS domains, the extent to which tau influences each specific NPS domain remains unclear. Here, we aim to investigate the association of tau and NPS domains in the AD continuum.

Clinical Manifestations.

Background: Early-Onset Alzheimer's Disease (EOAD) is a rare condition that affects only 5% of patients with Alzheimer's Disease (AD). At present, only basic information is known about the impact of AD risk variants on EOAD, and the effects of more subtle genetic contributions to cognitive decline have yet to be investigated. Genetic variants for brain derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) have both been implicated in cognitive change (Fiocco et al.

Clinical Manifestations.

Background: Early Onset Alzheimer's Disease (EOAD) is a rare condition that manifests prior to the age of 65, and affects approximately 5% of patients with Alzheimer's disease. The Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) is the largest prospectively-evaluated cohort of participants with sporadic EOAD in the United States, initiated to better understand the features of this condition. The current analyses sought to examine longitudinal cognitive trajectories of patients with EOAD over time.

Clinical Manifestations.

Background: Pathological changes of Alzheimer's disease (AD) occur in the locus coeruleus (LC) years before clinical symptoms. This may affect LC activity that can be indexed by changes in pupil dilation. AD also disrupts connections between related but functionally distinct cortical areas leading to visual feature binding deficits.

Clinical Manifestations.

Background: Informant reports can complement standardized cognitive assessment and improve accuracy of dementia diagnosis. Although informant reports correlate moderately with objective measures of decline, the influence of informant factors, such as gender, on these relationships is unclear. This study assessed the hypothesis that informant gender would emerge as an independent predictor in the relationship between informant ratings of cognitive function (i.

Clinical Manifestations.

Background: Subjective cognitive concerns (SCC) are possibly one of the earliest clinical symptoms of dementia. There is growing interest in applying mobile app-based assessment to remotely screen for cognitive status in preclinical dementia, but the relationship between SCC and relevant mobile assessment metrics remains unclear. To address this gap, we characterize the relationship between SCC and adherence, satisfaction, and performance on digital cognitive assessment in cognitively unimpaired older adults.

Clinical Manifestations.

Background: Early-onset Alzheimer's disease (EOAD) manifests prior to the age of 65. Clinical presentation of EOAD is distinct from that of late-onset Alzheimer's disease, and is characterized as having a more aggressive disease course with greater heterogeneity. Recent publications from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) described their sample as predominantly amnestic, though this phenotypic description was based solely on clinical judgment.

Clinical Manifestations.

Background: "SuperAgers" (SA) are older adults who perform significantly better than their peers and comparable to young adults on objective memory measures. Longitudinal studies show that many do not maintain their SA status over time. The fluctuation in SA stability may reflect changes in executive functioning, hypothesized to contribute to variance of episodic memory scores in SA.

Clinical Manifestations.

Background: The newly proposed criteria by the AA working group incorporates both biological and clinical stages to characterize the progression of AD. In this study, we aim to evaluate the agreement between these two complementary systems.

Methods: Using 188 participants from McGill TRIAD and 139 from the HEAD cohorts, we categorized participants into biological (0-4) and clinical (0-4) stages using amyloid PET, tau PET(MK-6240), and clinical measures as described by the working group.