<b><i>Background:</i></b> Alzheimer disease (AD) is a chronic neurodegenerative disorder with complex pathophysiology that affects over 50 million people worldwide. Most drug therapies, to date, have focused on targeting the amyloid-beta (Aβ) pathway, but clinical outcomes of anti-Aβ antibodies have been unsuccessful and unable to meet their primary endpoints. Similar trends have also been observed in treatments that target the tau pathway. <b><i>Summary:</i></b> This paper reviews recent anti-Aβ passive monotherapies, since Bapineuzumab, that have progressed to phase 3 clinical trials. Specifically, we discuss the 4 clinical trial programs of Solanezumab (targets Aβ monomers), Aducanumab (targets Aβ oligomers and plaques), Crenezumab (targets Aβ oligomers), and Gantenerumab (targets Aβ fibrils) which are all exogenous monoclonal antibodies. We conclude with potential reasons for why they have not met their primary endpoints and discuss lessons learnt from these trials. <b><i>Key Message:</i></b> Future disease-modifying trials (DMTs) for AD should be conducted in asymptomatic, Aβ-positive individuals. Moreover, potential additive and/or synergistic benefits focusing on anti-Aβ and anti-tau drug combinations merit further investigation.
BACKGROUND: Awake craniotomy (AC) enables real-time monitoring of cortical and subcortical functions when lesions are in eloquent brain areas. AC patients are exposed to various preoperative, intraoperative, and postoperative stressors, which might affect their mental health. OBJECTIVE: To conduct a systematic review to better understand stress, anxiety, and depression in AC patients. METHODS: PubMed, Scopus, and Web of Science databases were searched from January 1, 2000, to April 20, 2022, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. RESULTS: Four hundred forty-seven records were identified that fit our inclusion and exclusion criteria for screening. Overall, 24 articles consisting of 1450 patients from 13 countries were included. Sixteen studies (66.7%) were prospective, whereas 8 articles (33.3%) were retrospective. Studies evaluated stress, anxiety, and depression during different phases of AC. Twenty-two studies (91.7%) were conducted on adults, and 2 studies were on pediatrics (8.3 %). Glioma was the most common AC treatment with 615 patients (42.4%). Awake-awakeawake and asleep-awake-asleep were the most common protocols, each used in 4 studies, respectively (16.7%). Anxiety was the most common psychological outcome evaluated in 19 studies (79.2%). The visual analog scale and self-developed questionnaire by the authors (each n = 5, 20.8%) were the most frequently tools used. Twenty-three studies (95.8%) concluded that AC does not increase stress, anxiety, and/or depression in AC patients. One study (4.2%) identified younger age associated with panic attack. CONCLUSION: In experienced hands, AC does not cause an increase in stress, anxiety, and depression; however, the psychiatric impact of AC should not be underestimated.
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