Neurochemical changes underlying cognitive impairment in olfactory bulbectomized rats and the impact of the mGlu5-positive allosteric modulator CDPPB

2021 ◽  
pp. 147577
Author(s):  
Agata Płoska ◽  
Paulina Cieślik ◽  
Anna Siekierzycka ◽  
Leszek Kalinowski ◽  
Joanna M Wierońska
Author(s):  
Mark Walzer ◽  
Ruishan Wu ◽  
Maha Ahmad ◽  
Jon Freeman ◽  
Gary Zammit ◽  
...  

Abstract Rationale Previous research suggests that sleep polysomnography and EEG endpoints can be used to assess GABAergic activity; however, the impact of GABAB receptor positive allosteric modulators on sleep endpoints remains unclear. Objectives This phase 1 study compared a single dose of ASP8062 (35 mg or 70 mg), a GABAB receptor positive allosteric modulator, with placebo and paroxetine (40 mg). Methods Healthy adult volunteers were randomized to four treatments (35 mg ASP8062, 70 mg ASP8062, paroxetine 40 mg, or matching placebo), each separated by a 14-day washout. Primary endpoints obtained by polysomnography were time in stage N3 or SWS and time in rapid eye movement (REM) sleep. Secondary endpoints included impact on sleep stages and electroencephalography parameters, pharmacokinetics, nighttime growth hormone (GH), and safety/tolerability. Results In 20 randomized volunteers, ASP8062 led to a significant and seemingly dose-dependent increase in SWS over the entire night; this increase was mainly observed during the first third of the night. ASP8062 did not impact time in REM sleep. Paroxetine had no effect on SWS but produced a significant reduction in time spent in REM sleep. A dose-dependent trend in increased GH release was also observed with ASP8062. Headache and nausea were the most commonly reported treatment-emergent adverse events (TEAEs) for ASP8062; most TEAEs were mild in severity. Conclusions Single-dose ASP8062 (35 and 70 mg) appeared to result in CNS penetration and enhanced GABAergic activity as measured by increases in slow-wave sleep and growth hormone release.


2020 ◽  
Vol 477 (2) ◽  
pp. 459-459
Author(s):  
Lalith K. Chaganti ◽  
Shubhankar Dutta ◽  
Raja Reddy Kuppili ◽  
Mriganka Mandal ◽  
Kakoli Bose

2020 ◽  
Author(s):  
Erico Castro-Costa ◽  
Jerson Laks ◽  
Cecilia Godoi Campos ◽  
Josélia OA Firmo ◽  
Maria Fernanda Lima-Costa ◽  
...  

2020 ◽  
Author(s):  
Qing Zhao ◽  
Pei Chen ◽  
Yu Zhang ◽  
Haining Liu ◽  
Xianwen Li

BACKGROUND Mobile health application has become an important tool for healthcare systems. One such tool is the delivery of assisting in people with cognitive impairment and their caregivers. OBJECTIVE This scoping review aims to explore and evaluate the existing evidence and challenges on the use of mHealth applications that assisting in people with cognitive impairment and their caregivers. METHODS Nine databases, including PubMed, EMBASE, Cochrane, PsycARTICLES, CINAHL, Web of Science, Applied Science & Technology Source, IEEE Xplore and the ACM Digital Library were searched from inception through June 2020 for the studies of mHealth applications on people with cognitive impairment and their caregivers. Two reviewers independently extracted, checked synthesized data independently. RESULTS Of the 6101 studies retrieved, 64 studies met the inclusion criteria. Three categories emerged from this scoping review. These categories are ‘application functionality’, ‘evaluation strategies’, ‘barriers and challenges’. All the included studies were categorized into 7 groups based on functionality: (1) cognitive assessment; (2) cognitive training; (3) life support; (4) caregiver support; (5) symptom management; (6) reminiscence therapy; (7) exercise intervention. The included studies were broadly categorized into four types: (1) Usability testing; (2) Pilot and feasibility studies; (3) Validation studies; and (4) Efficacy or Effectiveness design. These studies had many defects in research design such as: (1) small sample size; (2) deficiency in active control group; (3) deficiency in analyzing the effectiveness of intervention components; (4) lack of adverse reactions and economic evaluation; (5) lack of consideration about the education level, electronic health literacy and smartphone proficiency of the participants; (6) deficiency in assessment tool; (7) lack of rating the quality of mHealth application. Some progress should be improved in the design of smartphone application functionality, such as: (1) the design of cognitive measurements and training game need to be differentiated; (2) reduce the impact of the learning effect. Besides this, few studies used health behavior theory and performed with standardized reporting. CONCLUSIONS Preliminary results show that mobile technologies facilitate the assistance in people with cognitive impairment and their caregivers. The majority of mHealth application interventions incorporated usability outcome and health outcomes. However, these studies have many defects in research design that limit the extrapolation of research. The content of mHealth application is urgently improved to adapt to demonstrate the real effect. In addition, further research with strong methodological rigor and adequate sample size are needed to examine the feasibility, effectiveness, and cost-effectiveness of mHealth applications for people with cognitive impairment and their caregivers.


Sign in / Sign up

Export Citation Format

Share Document