Antidepressants and Weight Gain: An Update on the Evidence and Clinical Implications.

Purpose Of Review: To highlight recent research on antidepressant use and weight change and explore best clinical practices for reducing weight gain and obesity risk in individuals with depression.

Recent Findings: Research on antidepressant use and weight gain suggests that genetic and biological factors including metabolizer phenotypes and inflammation can help to predict an individual's threshold for weight change among specific agents. For individuals with increased susceptibility to metabolic complications, medications including bupropion, fluoxetine, and newer agents (e.

Creating a predictive model and online calculator for high-value care outcomes following glioblastoma resection: incorporating neighborhood socioeconomic status index.

Purpose: Social determinants of health including neighborhood socioeconomic status, have been established to play a profound role in overall access to care and outcomes in numerous specialized disease entities. To provide glioblastoma multiforme (GBM) patients with high-quality care, it is crucial to identify predictors of hospital length of stay (LOS), discharge disposition, and access to postoperative adjuvant chemoradiation. In this study, we incorporate a novel neighborhood socioeconomic status index (NSES) and develop three predictive algorithms for assessing post-operative outcomes in GBM patients, offering a tool for preoperative risk stratification of GBM patients.

Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia as a Presentation of a Novel DNMT1 Mutation.

A 50-year-old woman with a 20-year history of gait instability presented with new-onset vertigo and oscillopsia. Examination revealed bilateral vestibular loss, cerebellar ataxia, sensory neuropathy, a "yes-yes" head tremor, nystagmus and a family history of a similar syndrome. Genetic testing for cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (RFC1) was negative, but whole exome sequencing identified a novel mutation in the DNA methyltransferase 1 (DNMT1) gene, broadening the differential diagnosis for this phenotype.

Evolving concepts in intracranial pressure monitoring - from traditional monitoring to precision medicine.

A wide range of acute brain injuries, including both traumatic and non-traumatic causes, can result in elevated intracranial pressure (ICP), which in turn can cause further secondary injury to the brain, initiating a vicious cascade of propagating injury. Elevated ICP is therefore a neurological injury that requires intensive monitoring and time-sensitive interventions. Patients at high risk for developing elevated ICP undergo placement of invasive ICP monitors including external ventricular drains, intraparenchymal ICP monitors, and lumbar drains.

Mathematic Modeling of Tumor Growth During [Lu]Lu-PSMA Therapy: Insights into Treatment Optimization.

The treatment regimen for [Lu]Lu-prostate-specific membrane antigen (PSMA) 617 therapy follows that of chemotherapy: 6 administrations of a fixed activity, each separated by 6 wk. Mathematic modeling can be used to test the hypothesis that the current treatment regimen for a radiopharmaceutical modality is suboptimal. A mathematic model was developed to describe tumor growth during [Lu]Lu-PSMA therapy.

Variability of Psoriatic Arthritis Impact of Disease questionnaire (PsAID12) thresholds in psoriatic arthritis: data from the ReFlaP study.

Objectives: To explore thresholds for the Psoriatic Arthritis (PsA) Impact of Disease questionnaire (PsAID12) score against disease activity measures in an observational setting, in patients with PsA.

Methods: The baseline data from the ReFlaP observational, prospective, multicentre and international study was used (NCT03119805). Cutoffs for PsAID12 were determined against disease activity scores, defining disease impact states (ie remission, low impact, moderate impact and high impact).

Group 3 Innate Lymphoid Cells: A Potential Therapeutic Target for Steroid Resistant Asthma.

Asthma is a chronic airway inflammatory disease that affects millions globally. Although glucocorticoids are a mainstay of asthma treatment, a subset of patients show resistance to these therapies, resulting in poor disease control and increased morbidity. The complex mechanisms underlying steroid-resistant asthma (SRA) involve Th1 and Th17 lymphocyte activity, neutrophil recruitment, and NLRP3 inflammasome activation.

Basic Science and Pathogenesis.

Background: Emerging evidence support the notion that loss of splicing repression by TDP-43, an RNA binding protein that was first implicated in ALS-FTD, underlies their pathogenesis. Previously, we showed that delivery of an AAV9 vector at early postnatal day expressing a fusion protein, termed CTR comprised of the N-terminal region of TDP-43 and an unrelated splicing repressor termed RAVER1 complemented the loss of TDP-43 in mice lacking TDP-43 in spinal motor neurons (ChAT-IRES-Cre;tardbp mice). To translate this potential therapeutic strategy to the clinic, it will be important to demonstrate benefit of such AAV delivery of CTR to motor neurons in adult mice.

Basic Science and Pathogenesis.

Background: Cerebral amyloid angiopathy (CAA), defined as the accumulation of amyloid in cerebral blood vessels causing alterations in the blood brain barrier (BBB) and the gliovascular unit, occurs in over 85% of Alzheimer's disease (AD) cases, positioning CAA as one of the strongest vascular contributors to age-related cognitive decline. However, the specific mechanisms in the microvasculature that become altered due to amyloid deposition and its downstream effects on the brain are complex and incompletely understood. A spatial transcriptomic analysis comparing pathways affected in the gliovascular niche differently in the presence of vascular amyloid could provide critical insight into the mechanisms underlying cerebrovascular changes involved in the deposition of Amyloid in the cerebrovasculature.

Basic Science and Pathogenesis.

Background: "SuperAgers" are older adults (ages 80+) whose cognitive performance resembles that of adults in their 50s to mid-60s. Factors underlying their exemplary aging are underexplored in large, racially diverse cohorts. Using eight cohorts, we investigated the frequency of APOE genotypes in SuperAgers compared to middle-aged and older adults.

Basic Science and Pathogenesis.

Background: Tau aggregates, a hallmark of Alzheimer's disease (AD) and other tauopathies, spread throughout the brain, contributing to neurodegeneration. How this propagation occurs remains elusive. Previous research suggests that tau-seed interactors play a crucial role.

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.

Basic Science and Pathogenesis.

Background: While immune function is known to play a mechanistic role in Alzheimer's disease (AD), whether immune proteins in peripheral circulation influence the rate of amyloid-b (Aβ) progression remains unknown.

Method: Using the Baltimore Longitudinal Study of Aging (BLSA; n = 196; mean follow-up: 5 years/4 scans), we identified immune-related proteins in plasma (candidate proteins) related to rates of change in cortical Aβ levels, as measured by C-PiB PET. Along with identifying genetic variants that contributed to candidate protein associations, characterizing their relationships with tau-PET and changes in ADRD biomarkers (Aβ, NfL, GFAP, pTau-181), and assessing their expression patterns in human microglia, we leveraged data from the Atherosclerosis Risk in Communities (ARIC) study to determine if changes in candidate protein levels precede Ab = β onset (n = 272), and whether they predict 20-year dementia risk during mid-life (n = 11,596) and 8-year dementia risk during late-life (n = 4,288).

Basic Science and Pathogenesis.

Background: Abnormal brain insulin signaling has been associated with Alzheimer's disease pathology and a faster rate of late-life cognitive decline. However, the underlying mechanisms remain unclear. In this study, we examined whether AD-related cortical proteins identified using targeted-proteomics play a role in the association of brain insulin signaling and cognitive decline.

Basic Science and Pathogenesis.

Background: By 2050 the number of Alzheimer's Disease (AD) patients is projected to exceed 150 million worldwide. AD is an incurable, insufficiently understood, and devastating neurodegenerative disease, with high patient heterogeneity in terms of progression, clinical manifestation (including neuropsychiatric symptoms, NPS) and, importantly, responsiveness to treatment options.[1] In the last 20 years, 98% of clinical trials for AD have failed, highlighting the urgent need to drastically change pre-clinical research to develop better predictors of drug safety and effectiveness.

Basic Science and Pathogenesis.

Background: TDP-43 proteinopathy, initially discovered in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), coexists with tauopathy in a variety of neurodegenerative disorders, including Alzheimer's Disease (AD). While such co-pathology is strongly associated with worsened neurodegeneration and steeper cognitive decline, how these two pathologies influence each other to exacerbate neuron loss remains elusive. That loss of TDP-43 splicing repression occurring in presymptomatic ALS-FTD suggests that loss of TDP-43 function could facilitate the pathological conversion of tau to accelerate tauopathy and neuron loss.

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.

Background: Although the rate of Alzheimer's disease (AD) in African-ancestry (AA) Americans is higher than that of persons from European-ancestry (EA) populations, AA participants have been underrepresented in AD neuropathological studies.

Method: Utilizing the AD Research Centers (ADRC) infrastructure, we obtained AA donor pre-frontal cortex (PFC) tissue from brain repositories of 12 ADRC and generated bulk RNA sequencing (RNA-seq) data for 179 samples that met QC and inclusion criteria. Previously generated PFC RNAseq data were obtained for 28 additional AA donors from the Columbia University ADRC.

Clinical Manifestations.

Background: Hearing loss is highly prevalent and can have significant consequences for older adults aging with cognitive impairment. However, few older adults use hearing aids and disparities in care exist by race, ethnicity, and socioeconomic position. To understand the intersection of hearing loss and cognitive impairment with the ultimate goal of developing an affordable, accessible hearing care intervention responsive to the needs of end-users, a series of semi-structured interviews was conducted.

Clinical Manifestations.

Background: Higher level of cognitive reserve (CR), measured using proxies such as years of education or literacy, is associated with reduced risk of Mild Cognitive Impairment (MCI) and dementia. Little is known about how CR and other lifestyle factors impact non-cognitive outcomes, including depression and other neuropsychiatric symptoms (e.g.

Clinical Manifestations.

Background: How clinicians discuss, document, and diagnose health concerns within a visit shapes patient perceptions of their health conditions. Undiagnosed hearing loss among older adults with dementia or cognitive concerns may exacerbate neuropsychiatric symptoms and care challenges. This study investigates clinician documentation of hearing concerns and whether documentation, diagnosis, and referral vary for older adults with dementia/cognitive concerns.

Clinical Manifestations.

Background: Although it is well established that lower cognitive performance, on average, is associated with a greater risk of developing Alzheimer's disease (AD) dementia, it is unclear whether distinct cognitively-defined subgroups exist among non-demented older adults and whether such profiles map onto distinct AD neuroimaging measure profiles.

Method: The sample consisted of 167 non-demented older adults from the BIOCARD study with comprehensive neuropsychological and clinical evaluations, amyloid PET and brain MRI scans. The MRI measure included: global cortical volume in AD-signature regions and a medial-temporal lobe composite; resting-state functional connectivity within 5 large-scale cognitive networks; global white matter microstructure, index by fractional anisotropy (FA) and radial diffusion (RD) on DTI scans; and global white matter hyperintensity (WMH) volume on FLAIR scans.