Blood biomarker profiles in young-onset neurocognitive disorders: A cohort study.

Introduction: Young-onset neurocognitive symptoms result from a heterogeneous group of neurological and psychiatric disorders which present a diagnostic challenge. To identify such factors, we analysed the Biomarkers in Younger-Onset Neurocognitive Disorders cohort, a study of individuals <65 years old presenting with neurocognitive symptoms for a diagnosis and who have undergone cognitive and biomarker analyses.

Methods: Sixty-five participants (median age at assessment of 56 years, 45% female) were recruited during their index presentation to the Royal Melbourne Hospital Neuropsychiatry Centre, a tertiary specialist service in Melbourne, Australia, and categorized as either early-onset Alzheimer's disease ( = 18), non-Alzheimer's disease neurodegeneration ( = 23) or primary psychiatric disorders ( = 24).

Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival.

Glioma is a highly fatal and heterogeneous brain tumor with few known risk factors. Our study examines genetically predicted variability in blood cell indices in relation to glioma risk and survival in 3418 cases and 8156 controls. We find that increased platelet to lymphocyte ratio (PLR) confers an increased risk of glioma (odds ratio (OR) = 1.

Identifying the most effective acute stress induction methods for producing SAM- and HPA-related physiological responses: a meta-analysis.

Background And Objectives: Laboratory-based stress inductions are commonly used to elicit acute stress but vary widely in their procedures and effectiveness. We compared the effects of stress induction techniques on measures of two major biological stress systems: the early sympathetic-adrenal-medullary (SAM) and the delayed hypothalamic-pituitary-adrenal (HPA) axis response.

Design: A review and meta-analysis to examine the relationship between stress induction techniques on cardiorespiratory and salivary measures of SAM and HPA system activity.

Repurposing of a gill gene regulatory program for outer ear evolution.

How novel structures emerge during evolution has long fascinated biologists. A dramatic example is how the diminutive bones of the mammalian middle ear arose from ancestral fish jawbones. In contrast, the evolutionary origin of the outer ear, another mammalian innovation, remains a mystery, in part because it is supported by non-mineralized elastic cartilage rarely recovered in fossils.

Biological sex matters in brain aging.

Every cell in the body has a biological sex. The expansion of aging research to investigate female- and male-specific biology heralds a major advance for human health. Unraveling and harnessing mechanistic etiologies of sex differences may reveal new diagnostics and therapeutics for the aging brain.

Association of Medial Temporal Lobe Cerebrovascular Reactivity and Memory Function in Older Adults With and Without Cognitive Impairment.

Background And Objectives: Cerebrovascular reactivity (CVR) represents the ability of cerebral blood vessels to regulate blood flow in response to vasoactive stimuli and is related to cognition in cerebrovascular and neurodegenerative conditions. However, few studies have examined CVR in the medial temporal lobe, known to be affected early in Alzheimer disease and to influence memory function. We aimed to examine whether medial temporal CVR is associated with memory function in older adults with and without mild cognitive impairment (MCI).

A data-driven model of disability progression in progressive multiple sclerosis.

This study applies the Gaussian process progression model, a Bayesian data-driven disease progression model, to analyse the evolution of primary progressive multiple sclerosis. Utilizing data from 1521 primary progressive multiple sclerosis participants collected within the International Progressive Multiple Sclerosis Alliance Project, the analysis includes 18 581 longitudinal time-points (average follow-up time: 28.2 months) of disability assessments including the expanded disability status scale, symbol digit modalities, timed 25-foot-walk, 9-hole-peg test and of MRI metrics such as T1 and T2 lesion volume and normalized brain volume.

Who will benefit from vorasidenib? Review of data from the literature and open questions.

The clinical efficacy of isocitrate dehydrogenase (IDH) inhibitors in the treatment of patients with grade 2 IDH-mutant (mIDH) gliomas is a significant therapeutic advancement in neuro-oncology. It expands treatment options beyond traditional radiation therapy and cytotoxic chemotherapy, which may lead to significant long-term neurotoxic effects while extending patient survival. The INDIGO study demonstrated that vorasidenib, a pan-mIDH inhibitor, improved progression-free survival for patients with grade 2 mIDH gliomas following surgical resection or biopsy compared to placebo and was well tolerated.

Modifying Informed Consent to Help Address Functional Unmasking in Psychedelic Clinical Trials.

Importance: There is unprecedented clinician, industry, and patient interest in the therapeutic development of psychedelic drugs. This is due to a combination of promising clinical trial results, positive media coverage, and the lack of novel pharmacologic treatments for psychiatric disorders in recent decades. However, the field faces a key methodological challenge: masking participants to treatment conditions in psychedelic clinical trials has been largely unsuccessful.

Rectangular Repetitive Transcranial Magnetic Monophasic vs Biphasic Stimulation for Major Depressive Disorder: A Randomized Controlled Pilot Trial.

Objectives: Biphasic sinusoidal repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation treatment that has been approved by the US Food and Drug Administration for treatment-resistant depression (TRD). Recent advances suggest that standard rTMS may be improved by altering the pulse shape; however, there is a paucity of research investigating pulse shape, owing primarily to the technologic limitations of currently available devices. This pilot study examined the feasibility, tolerability, and preliminary efficacy of biphasic and monophasic rectangular rTMS for TRD.

Dissemination of the Care Ecosystem Collaborative Care Model for Dementia.

Background: Dementia represents a growing healthcare challenge in the United States. The Care Ecosystem, an effective collaborative care model, bridges medical and social care needs for individuals with dementia. The purpose of this study was to describe how the Care Ecosystem has been disseminated and the lessons learned from this experience.

Priority Clinical Actions for Outpatient Management of Nonhospitalized Traumatic Brain Injury.

Outpatient care following nonhospitalized traumatic brain injury (TBI) is variable, and often sparse. The National Academies of Sciences, Engineering, and Medicine's 2022 report on highlighted the need to improve the consistency and quality of TBI care in the community. In response, the present study aimed to identify existing evidence-based guidance and specific clinical actions over the days to months following nonhospitalized TBI that should be prioritized for implementation in primary care.

Feasibility and psychometric quality of smartphone administered cognitive ecological momentary assessments in women with metastatic breast cancer.

Objective: Metastatic breast cancer (MBC) is associated with burdensome side effects, including cognitive changes that require ongoing monitoring. Cognitive ecological momentary assessments (EMAs) allow for assessment of individual cognitive functioning in natural environments and can be administered via smartphones. Accordingly, we sought to establish the feasibility, reliability, and validity of a commercially available cognitive EMA platform.

Ecological Momentary Assessment for Adolescents With Anorexia Nervosa and Their Parents/Caregivers in Family-Based Treatment.

Introduction: Studies have shown that early weight gain in family-based treatment (FBT) predicts treatment response in adolescents with anorexia nervosa (AN); however, research examining factors associated with early weight gain in FBT is limited. This study tested the feasibility and acceptability of ecological momentary assessment (EMA) in early FBT, particularly to capture momentary data on family climate during mealtimes.

Methods: Using multiple methods, quantitative (EMA) and qualitative (interviews) data were collected in the first 4 weeks of FBT.

Functional germline variants in DNA damage repair pathways are associated with altered survival in adults with glioma treated with temozolomide.

Background: Temozolomide (TMZ) treatment has demonstrated, but variable, impact on glioma prognosis. This study examines associations of survival with DNA repair gene germline polymorphisms among glioma patients who did and did not have TMZ treatment. Identifying genetic markers which sensitize tumor cells to TMZ could personalize therapy and improve outcomes.

A single-cell compendium of human cerebrospinal fluid identifies disease-associated immune cell populations.

Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples.

The fungal gut microbiota in pediatric-onset multiple sclerosis.

Evidence suggests that the gut microbiome may play a role in multiple sclerosis (MS). However, the majority of the studies have focused on gut bacterial communities; none have examined the fungal microbiota (mycobiota) in persons with pediatric-onset multiple sclerosis (POMS). We examined the gut mycobiota in persons with and without POMS through a cross-sectional examination of the gut mycobiota from 46 participants' stool samples (three groups: 18 POMS, 13 acquired monophasic demyelinating syndromes [monoADS], and 15 unaffected controls).

Quantitative evaluation of electrographic response to electroconvulsive therapy in super-refractory status epilepticus.

Objective: Electroconvulsive therapy (ECT) has been occasionally applied as a treatment for super-refractory status epilepticus (SRSE). However, the effects of ECT on electrographic activity and related clinical outcomes are largely unknown. Here, we use quantitative approaches on electroencephalography (EEG) data to evaluate the neurophysiological influences of ECT and how they may relate to patient survival.

Identification of a T2-hyperintense Perivascular Space in Brain Arteriovenous Malformations.

Background/aim: Brain arteriovenous malformations (AVMs) are vascular malformations characterized by dysmorphic, aberrant vasculature. During previous surgeries of compact nidus brain AVMs (representing the majority of cases), we have observed a "shiny" plane between nidal and perinidal AVM vessels and the surrounding grey and white matter and hypothesized that preoperative neuroimaging of brain AVMs may show a neuroradiological correlate of these intraoperative observations.

Patients And Methods: We retrospectively reviewed and analyzed multiplanar and multisequence 3-Tesla magnetic resonance (3T MR) imaging in five consecutive brain AVMs with special attention on imaging characteristics of the brain-AVM interface, i.

Gut-derived appetite regulating hormones across the anorexia nervosa spectrum.

Background: Appetite-regulating hormones are implicated in anorexia nervosa (AN) pathophysiology, however, data are limited for appetite-regulating hormones across the AN weight spectrum. We aimed to investigate fasting and post-prandial concentrations of appetite-regulating hormones - peptide YY (PYY), cholecystokinin (CCK), and ghrelin - among adolescent and young adult females across the AN weight spectrum, specifically those with AN and Atypical AN, and healthy controls (HC).

Methods: Participants (N = 95; ages 11-22 years) included 33 with AN, 25 with Atypical AN, and 37 HC.

Disrupted callosal connectivity underlies long-lasting sensory-motor deficits in an NMDAreceptor antibody encephalitis mouse model.

NMDA receptor mediated autoimmune encephalitis (NMDAR-AE) frequently results in persistent sensory-motor deficits, especially in children, yet the underlying mechanisms remain unclear. This study investigated the long- term effects of exposure to a patient-derived GluN1-specific monoclonal antibody (mAb) during a critical developmental period (from postnatal day 3 to day 12) in mice. We observed long-lasting sensory-motor deficits characteristic of NMDAR-AE, along with permanent changes in callosal axons within the primary somatosensory cortex (S1) in adulthood, including increased terminal branch complexity.

Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer's disease, and primary age-related tauopathy hippocampi.

Introduction: Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition.

Methods: We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non-NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5).

Results: There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders.