Expert Review of Neurotherapeutics最新文献

Introduction: The importance of cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) diagnosis is rapidly increasing, and there is a growing interest in the use of CSF biomarkers in monitoring the response to therapy, especially in the light of newly available approaches to the therapy of neurodegenerative diseases.

Areas covered: In this review we discuss the most relevant measures of neurodegeneration that are being used to distinguish patients with AD from healthy controls and individuals with mild cognitive impairment, in order to provide an overview of the latest information available in the scientific literature. We focus on markers related to amyloid processing, markers associated with neurofibrillary tangles, neuroinflammation, neuroaxonal injury and degeneration, synaptic loss and dysfunction, and markers of α-synuclein pathology.

Expert opinion: In addition to neuropsychological evaluation, core CSF biomarkers (Aβ₄₂, t-tau, and p-tau181) have been recommended for improvement of timely, accurate and differential diagnosis of AD, as well as to assess the risk and rate of disease progression. In addition to the core CSF biomarkers, various other markers related to synaptic dysfunction, neuroinflammation, and glial activation (neurogranin, SNAP-25, Nfl, YKL-40, TREM2) are now investigated and have yet to be validated for future potential clinical use in AD diagnosis.

Introduction: Brain atrophy is a well-established MRI outcome for predicting clinical progression and monitoring treatment response in persons with multiple sclerosis (pwMS) at the group level. Despite the important progress made, the translation of brain atrophy assessment into clinical practice faces several challenges.

Areas covered: In this review, the authors discuss technical- and subject-related barriers for implementing brain atrophy assessment as part of the clinical routine at the individual level. Substantial progress has been made to understand and mitigate technical barriers behind MRI acquisition. Numerous research and commercial segmentation techniques for volume estimation are available and technically validated, but their clinical value has not been fully established. A systematic assessment of subject-related barriers, which include genetic, environmental, biological, lifestyle, comorbidity, and aging confounders, is critical for the interpretation of brain atrophy measures at the individual subject level. Educating both medical providers and pwMS will help better clarify the benefits and limitations of assessing brain atrophy for disease monitoring and prognosis.

Expert opinion: Integrating brain atrophy assessment into clinical practice for pwMS requires overcoming technical and subject-related challenges. Advances in MRI standardization, artificial intelligence, and clinician education will facilitate this process, improving disease management and potentially reducing long-term healthcare costs.

Introduction: With the increasing prevalence of atrial fibrillation (AF), it entails expanding oral anticoagulants (OACs) use, carrying a higher risk of associated hemorrhagic events, including intracranial hemorrhage (ICH). Despite advances in OACs development with a better safety profile and reversal agent for these anticoagulants, there is still no consensus on the optimal management of patients with OACs-associated ICH.

Areas covered: In this review, the authors have carried out an exhaustive search on the advances in recent years. The authors provide an update on the management of ICH in anticoagulated patients, as well as an update on the latest evidence on anticoagulation resumption, recent therapeutic strategies, and investigational drugs that could play a role in the future.

Expert opinion: Following an ICH event in an anticoagulated patient, a comprehensive clinical evaluation is imperative. Anticoagulation should be promptly withdrawn and reversed. Once the patient is stabilized, a reintroduction of anticoagulation should be considered, typically within a timeframe of 4-8 weeks, if feasible. If re-anticoagulation is not possible, alternative options such as Left Atrial Appendage Occlusion are available.

Introduction: Gantenerumab is a monoclonal antibody targeting amyloid β protein (Aβ) in early Alzheimer's disease (AD). The authors sought to evaluate gantenerumab safety and efficacy in early AD patients.

Methods: MEDLINE, Embase, and Cochrane databases were systematically searched until 2 December 2023. Data were examined using the Mantel-Haenszel method and 95% confidence intervals (CIs). Meta-regression analysis was conducted to evaluate a possible link between baseline Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) and amyloid-related imaging abnormalities (ARIA) at follow-up. R, version 4.2.3, was used for statistical analysis.

Results: A total of 4 RCTs and 2848 patients were included, of whom 1580 (55%) received subcutaneous gantenerumab. Concerning clinical scores, the placebo group achieved better rates of change in the Disease Assessment Scale (ADAS-Cog13) (SMD -0.11; 95% CI -0.19- -0.03; p = 0.008569; I² = 0%). Gantenerumab was strongly associated with the occurrence of ARIA-E and ARIA-H: (19.67% vs. 2.31%; RR 9.46; 95% CI 5.55-16.11; p = <0.000001; I² = 10%) and (21.95% vs. 12.38%; RR 1.79; 95% CI 1.50-2.13; p = <0.000001; I² = 0%), respectively.

Discussion: In this meta-analysis, consistent results suggest that gantenerumab is not safe and efficient for early AD, showing no improvement in clinical scores for AD and being associated with the occurrence of ARIA-E and ARIA-H.

Introduction: Major Depressive Disorder (MDD) is a common mental health disorder marked by sadness, hopelessness, and anhedonia. Various therapies exist, but their effectiveness is limited. Dextromethorphan hydrobromide combined with bupropion hydrochloride (Auvelity®) is a recently approved alternative for treating this condition in adults.

Areas covered: This review summarizes the neurobiology of major depression and delves into the pharmacology, efficacy, safety, and tolerability of dextromethorphan plus bupropion in adult patients. It is based on observational studies, clinical trials, and other secondary studies obtained through systematic literature searches.

Expert opinion: The combination of bupropion and dextromethorphan as a new pharmacotherapy for mental health is an interesting addition to the treatment options that can be used for MDD. The combination can be used in a range of scenarios, including as a first line therapy, as a second option when a patient has failed to achieve remission with a serotonin targeting agent, and for treatment resistant depression. Further research for other indications, including addiction disorders, may provide exciting results. Although a new combination, clinicians will be very familiar with both agents, increasing their acceptability. This pharmacotherapy also may bring increased impetus for discovering other combinations that may have beneficial synergistic effects.