Search results for " AD"

Frailty as a predictor of adverse outcomes in hospitalized older adults: A systematic review and meta-analysis.

2019

Frailty syndrome is prevalent among hospitalized older adults as are the occurrence of adverse outcomes. This systematic review and meta-analysis investigated whether frailty in older adults at hospital admission predicts adverse outcomes. Manual (ProQuest, conferences annals and references) and electronic searches (PUBMED, EMBASE, Web of Science, Lilacs, CINAHL, PsycINFO and Google Scholar) were performed. We included prospective studies of hospitalized older adults. Primary outcomes were functional decline at hospital discharge and mortality after discharge. Other data were considered secondary outcomes. Methodological quality was evaluated by the Quality Assessment Tool for Observational…

Interactive effects of aging and aerobic capacity on energy metabolism-related metabolites of serum, skeletal muscle, and white adipose tissue

2021

ABSTRACTAerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging and their interaction on metabolism, we utilized rat models of low and high intrinsic aerobic capacity (LCRs/HCRs) and assessed the metabolomics of serum, muscle, and white adipose tissue (WAT). We compared LCRs and HCRs at two time points: Young rats were sacrificed at 9 months, and old rats were sacrificed at 21 months. Targeted and semi-quantitative metabolomics analysis was performed on ultra-pressure Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS)…

The Early Indicators of Functional Decrease in Mild Cognitive Impairment

2016

OBJECTIVES: Motor deficiency is associated with cognitive frailty in patients with Mild Cognitive Impairments (MCI). In this study we aimed to test the integrity of the muscle synergy involved in an arm-pointing movement in MCI patients, non-impaired functionally. Thus, we were able to test the hypothesis that early motor indicators exist in this population at a preclinical level. METHODS: The electromyographic signals were collected for 11 muscles in 3 groups: Young Adults (YA), Aged Adults (AA), and MCI patients. The AA and MCI groups presented the same functional status. Each subject performed twenty arm-pointing movements from a standing position. RESULTS: The main differences were (1) …

2020

Healthy aging is associated with deterioration of the sensorimotor system, which impairs balance and somatosensation. However, the exact age-related changes in the cortical processing of sensorimotor integration are unclear. This study investigated primary sensorimotor cortex (SM1) oscillations in the 15-30 Hz beta band at rest and following (involuntary) rapid stretches to the triceps surae muscles (i.e., proprioceptive stimulation) of young and older adults. A custom-built, magnetoencephalography (MEG)-compatible device was used to deliver rapid (190°·s-1) ankle rotations as subjects sat passively in a magnetically-shielded room while MEG recorded their cortical signals. Eleven young (age…

Evidence of resistance training-induced neural adaptation in older adults

2021

The deleterious effects of aging on force production are observable from the age of 40 upwards, depending on the measure. Neural mechanisms contributing to maximum force production and rate of force development have been suggested as descending drive from supraspinal centers, spinal motoneuron excitability, and corticospinal inhibition of descending drive; all of which influence motor unit recruitment and/or firing rate. Resistance-trained Master athletes offer a good source of information regarding the inevitable effects of aging despite the countermeasure of systematic resistance-training. However, most evidence of neural adaptation is derived from longitudinal intervention studies in pre…

Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mP…

2016

Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal n…

Do β3-adrenoceptor agonists cause urinary bladder smooth muscle relaxation by inhibiting acetylcholine release?

2017

The mechanisms leading to improvement of overactive bladder syndrome upon treatment with a β3-adrenoceptor agonist remain controversial. New research points to a role of inhibition of neuronal acetylcholine release. Whether this occurs by a direct effect on prejunctional β3-adrenoceptors or indirectly by formation of adenosine and activation of A1 adenosine receptors is being discussed.

β3-Adrenoceptor agonists for overactive bladder syndrome: Role of translational pharmacology in a repositioning clinical drug development project

2016

β3-Adrenoceptor agonists were originally considered as a promising drug class for the treatment of obesity and/or type 2 diabetes. When these development efforts failed, they were repositioned for the treatment of the overactive bladder syndrome. Based on the example of the β3-adrenoceptor agonist mirabegron, but also taking into consideration evidence obtained with ritobegron and solabegron, we discuss challenges facing a translational pharmacology program accompanying clinical drug development for a first-in-class molecule. Challenges included generic ones such as ligand selectivity, species differences and drug target gene polymorphisms. Challenges that are more specific included changin…

β(3)‐Adrenoceptors in the normal and diseased urinary bladder—What are the open questions?

2019

β(3)‐Adrenoceptor agonists are used in the treatment of overactive bladder syndrome. Although the relaxant response to adrenergic stimulation in human detrusor smooth muscle cells is mediated mainly via β(3)‐adrenoceptors, the plasma concentrations of the therapeutic dose of mirabegron, the only clinically approved β(3)‐adrenoceptor agonist, are considerably lower than the EC(50) for causing direct relaxation of human detrusor, suggesting a mechanism of action other than direct relaxation of detrusor smooth muscle. However, the site and mechanism of action of β(3)‐adrenoceptor agonists in the bladder have not been firmly established. Postulated mechanisms include prejunctional suppression o…

A 300 IR sublingual tablet is an effective, safe treatment for house dust mite-induced allergic rhinitis: An international, double-blind, placebo-con…

2021

Background: Allergic rhinitis induced by house dust mites (HDMs) is a highly prevalent but often underdiagnosed and undertreated/untreated chronic disease. It often has a negative impact on sleep, work, leisure activities, and health-related quality of life. Allergen immunotherapy is a proven, safe treatment for respiratory allergies. Objective: We sought to assess the efficacy and safety of a 300 index of reactivity (IR) sublingual tablet formulation of Dermatophagoides pteronyssinus:Dermatophagoides farinae 1:1 extract in adolescents (aged >_12) and adults with moderate to severe HDM-induced allergic rhinitis. Methods: In a phase III, international, double-blind, placebo controlled, rando…