Neuroscience
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Review
"Current and emerging drug therapies in Alzheimer's disease: A pathophysiological Perspective".
The analytical and experimental investigation of several targets and biomarkers that help in explaining significant cognitive deficits, covering drug development and precision medicine aimed at different chronic neurodegenerative conditions such as Alzheimer's disease (AD), Parkinson's disease, synaptic dysfunction, brain damage from neuronal apoptosis, and other disease pathologies; this served as the foundation for all phase studies. The focus of current therapeutic approaches is on developing humanized antibodies, agonist and antagonist drugs, receptors, signaling molecules, major targeted drug-metabolizing enzymes, and other metabolites to treat neurodegeneration in the AD brain brought on by tau hyperphosphorylation, amyloid plagues, or other cholinergic effects. ⋯ Studies on the biotransformation of xenobiotic compounds and the metabolism of exogenous and endogenous substances are conducted under Phase I, Phase II, and Phase III trials because the pivotal pharmacokinetic properties of drugs, such as absorption, distribution, metabolism, and excretion (ADME), aid in understanding variations in the crucial improvement of various target drugs. This review also highlights the developments in soon-to-be genetically created targeted medications that may serve as ground-breaking treatments for cholinergic illnesses in the brains of AD patients and other neurodegenerative conditions.
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Heart failure (HF) frequently suffers from brain abnormalities and cognitive impairments. This study aims to investigate brain structure and function alteration in patients with chronic HF. This retrospective study included 49 chronic HF and 49 health controls (HCs). ⋯ Decreased GMV showed positive correlations with cognitive performance (r = 0.025-0.577, p = 0.025-0.001), while decreased fractional anisotropy was negatively correlated with anxiety scores (r = -0.339, p = 0.040) in patients with chronic HF. This study revealed that patients with chronic HF exhibited brain structure injury affecting gray matter and white matter, as well as FC abnormalities of brain regions responsible for cognition, sensorimotor and visual function. These findings suggest GMV could serve as a neuroimaging biomarker for cognitive impairments and a potential target for neuroprotective therapies in patients with chronic HF.
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Loneliness is intricately connected to social cognition, yet the precise brain mechanisms that underscore their relationship need further exploration. The present study employed a theory of mind processing task that engaged participants in assessing the trajectories of geometric shapes while undergoing fMRI scans. The comprehensive data pool encompassed loneliness assessments and brain imaging data from a cohort of 157 participants. ⋯ Furthermore, functional connectivity among the social network, the default mode network, and somatomotor networks emerged as crucial factors in prediction. Brain regions contributed strongly in prediction are involved in a variety of social cognitive processes, including intention inference, empathy, and information integration. The results illuminate the association between brain functional connectivity induced by social cognition and loneliness, which enhance the comprehensive understanding of this complex emotional state and may have implications for its diagnosis and intervention.
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Review Meta Analysis Comparative Study
Comparison of the efficacy of updated drugs for the treatment on the improvement of cognitive function in patients with Alzheimer 's disease: A systematic review and network meta- analysis.
The recent emergence of updated drugs for the treatment of Alzheimer's disease (AD) has produced encouraging cognitive and clinical results in clinical trials, but there is still controversy over how to choose effective treatment options among these numerous drugs. The purpose of this network meta-analysis (NMA) is to compare and rank these drugs based on their efficacy. ⋯ Donanemab and Lecanemab showed good efficacy in ADCS-ADL and CDR-SB, respectively. GV-971 is the best choice to improve ADAS cogs and NPI.
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Stroke is a serious condition often resulting in mortality or long-term disability, causing cognitive, memory, and motor impairments. A reduction in cerebral blood flow below critical levels defines the ischemic core and penumbra: the core undergoes irreversible damage, while the penumbra remains viable but functionally impaired. This functional impairment activates complex cell signaling pathways that determine cell survival or death, making the penumbra a key target for therapeutic interventions to prevent further damage. ⋯ While preclinical evidence supports the benefits of WβC activation, its role in human stroke requires further investigation. Additionally, the review discusses the potential adverse effects of prolonged WβC activation and suggests strategies to mitigate them. Overall, WβC signaling holds promise as a therapeutic target, offering insights into stroke pathophysiology and informing the development of novel treatment strategies.