Adults with Down syndrome are genetically predisposed to developing Alzheimer's disease after the age of 40. The cholinergic system, which is critical for cognitive functioning, known decline in and although first investigated individuals 40 years ago, remains relatively understudied. Existing studies suggest have an intact system at birth that declines through adulthood alongside development pathology. present study provides description terminals vivo non-demented adults utilizing...

<title>Abstract</title> The development of cholinergic neurotransmitter based cognitive enhancers for Alzheimer’s disease and other neuropsychiatric disorders have focused recently on allosteric modulation specific muscarinic acetylcholine receptor (mAChR) subtypes to reduce dose-limiting side-effects that been the hallmark earlier orthosteric mAChR agonists. VU0467319 (VU319) is an investigational positive modulator M₁ mAChR. A Phase 1 first-in-human study was conducted assessing...

Abstract BACKGROUND Adults with Down syndrome (DS) have increased risk of Alzheimer's disease (AD). The cholinergic system declines in AD, underlying many cognitive deficits. We investigated the relationship between amyloid accumulation and terminal density adults DS compared to amyloid‐matched controls. METHODS A total 15 non‐demented healthy controls were assessed for [ 18 F]‐FEOBV uptake differences relationships performance. RESULTS displayed greater than controls, a similar pattern....

Purpose: Research popularity and scope for the application of transcranial direct current stimulation have been steadily increasing yet many fundamental questions remain unanswered.We sought to determine if anodal either hemisphere leads improved performance contralateral hand and/or altered function ipsilateral hand, or affects movement preparation, in older subjects.Method: In this cross-over, double blind, sham controlled study, 34 healthy aged participants (age range 40-86) were...

Sensory over-responsivity (SOR) refers to excessively intense and/or prolonged behavioral responses environmental stimuli typically perceived as non-aversive. SOR is prevalent in several neurodevelopmental disorders, including chronic tic disorders (CTDs) and obsessive-compulsive disorder (OCD). Few studies have examined the extent clinical correlates of across limiting insights into phenomenon's transdiagnostic biological relevance. Such cross-disorder comparisons are particular interest...

Late-life depression (LLD) is characterized by poor antidepressant response and cognitive dysfunction. This study examined whether transdermal nicotine benefits mood symptoms performance in LLD.

Sensory hypersensitivity, defined as heightened awareness of and reactivity to external stimuli, is a bothersome symptom that affects up 80% adults with Tourette syndrome (TS). Such widespread prevalence suggests sensory hypersensitivity core feature the disorder, but its severity association other clinical features TS remain largely unexplored. Complicating matters, has been observed in two neurodevelopmental disorders commonly comorbid TS: obsessive-compulsive disorder (OCD) attention...

Anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has been proposed as a possible therapeutic rehabilitation technique for impairment. However, despite extensive investigation into effects of anodal tDCS on output, there is little information how affects response processes. In this study, we used cued go/nogo task with both directional and non-directional cues to assess dominant (left) prepared unprepared responses. Three experiments explored whether...

Anodal transcranial direct current stimulation (tDCS) over the motor cortex is considered a potential treatment for rehabilitation following stroke and other neurological pathologies. However, both context under which this effective underlying mechanisms remain to be determined. In study, we examined by anodal tDCS may affect performance recording event-related potentials (ERPs) during cued go/nogo task after dominant M1 in young adults (Experiment 1) non-dominant old 2). experiments, had no...

Abstract Adults with Down syndrome are genetically predisposed to developing Alzheimer’s disease after the age of 40. The cholinergic system, which is critical for cognitive functioning, known decline in and although first investigated individuals 40 years ago, remains relatively understudied. Existing studies suggest have an intact system at birth that declines through adulthood alongside development pathology. present study provides description terminals vivo non-demented adults utilizing...

Abstract Objective: Menopause is associated with increasing cognitive complaints and older women are at increased risk of developing Alzheimer disease compared to men. However, there difficulty in early markers using objective performance measures. We investigated the impact subjective on cortical structure a sample younger postmenopausal women. Methods: Data for this cross-sectional study were drawn from baseline visit longer double-blind examining estrogen-cholinergic interactions normal...

Event-related potential (ERP) studies using the task-switching paradigm show that multiple ERP components are modulated by activation of proactive control processes involved in preparing to repeat or switch task and reactive implementation current new task. Our understanding functional significance these has been hampered variability their robustness, as well temporal scalp distribution across studies. The aim this study is examine effect choice reference electrode spatial filter on number,...

Purpose Chemotherapy-related cognitive impairment (CRCI) is a distressing and increasingly recognized long-term sequela reported by breast cancer patients following treatment. There an urgent but unmet clinical need for treatments that improve CRCI. In this context, we proposed the use of novel enhancement strategy called Neuroflex to target CRCI experienced survivors. Methods The primary aim pilot study was evaluate feasibility acceptability Neuroflex, digital strategy, in gynecologic...

Aging is associated with increased prevalence of vascular health conditions. These are changes in the cardiac vasculature and detrimental to cerebral structure function, most strikingly white matter. Previous research has shown that arterial pulsatility related decreased matter microstructural organization impaired cognitive functioning. However, this relationship was only significant people cardiovascular risk factors. Conversely, absence factors thought relate better long-term health. This...

Abstract Background VU319 is an investigational positive allosteric modulator of the M 1 muscarinic acetylcholine receptor developed for cognitive enhancement in Alzheimer’s disease (AD) and other disorders. Cognitive tasks including test attention, speed, memory event‐related potentials (ERPs) were used during double‐blind, placebo controlled Single Ascending Dose (SAD) study VU319. The main pharmacodynamic objectives SAD to identify early markers functional engagement. Following ascending...

Transcranial direct current stimulation (tDCS) has been proposed as a tool to enhance stroke rehabilitation; however, evidence support its use is lacking. The aim of this study was investigate the effects anodal and cathodal tDCS on upper limb function in chronic patients. Twenty five participants were allocated receive 20 min 1 mA anodal, or sham cortical random, counterbalanced order. Patients assessors blinded intervention at each time point. primary outcome performance measured by Jebsen...

Older women are at increased risk of developing Alzheimer's disease compared to men. One proposed reason is that following menopause there a decline in estrogens. Estrogens important for cholinergic functioning and attenuate the impact antagonists on cognitive performance postmenopausal women. Self-reported or subjective complaints middle older age may represent harbinger those who endorse appear more likely develop future impairment. However, response individuals with after estrogen...

M1 is the primary muscarinic acetylcholine receptor (mAChR) subtype involved in domains of cognitive function impaired Alzheimer's disease. Previous orthosteric and allosteric agonists developed to activate mAChRs have failed clinical development due a lack true specificity for resulting dose-limiting adverse effects. We focused on modulation less highly conserved binding sites avoid these difficulties. Our investigational lead (VU319) has robust M1-mediated effects hippocampal synaptic...

Introduction Women are at a higher risk of developing Alzheimer’s disease (AD), and the decline in estrogens post-menopause is thought as factor increasing this risk. Estradiol (E2) important supporting cholinergic neuronal integrity, functioning may be negatively impacted following loss E2 post-menopause. The use exogenous has been observed to enhance cholinergically mediated cognitive performance healthy post-menopausal women, which indicates potentially protective mechanism. However,...