may contribute to cognitive dysfunction in patients with Alzheimer disease (AD).OBJECTIVE To determine the ability of the antiseizure drug levetiracetam to improve cognition in persons with AD. DESIGN, SETTING, AND PARTICIPANTSThe Levetiracetam for Alzheimer's Disease-Associated Network Hyperexcitability (LEV-AD) study was a phase 2a randomized double-blinded placebo-controlled crossover clinical trial of 34 adults with AD that was conducted at the

Frontotemporal dementia (FTD) rarely occurs in individuals under the age of 30, and genetic causes of early-onset FTD are largely unknown. The current report follows a 27 year-old patient with no significant past medical history presenting with two years of progressive changes in behavior, rushed speech, verbal aggression, and social withdrawal. MRI and FDG-PET imaging of the brain revealed changes maximally in the frontal and temporal lobes, which along with the clinical features, are consistent with behavioral variant FTD. Next generation sequencing of a panel of 28 genes associated with dementia and amyotrophic lateral sclerosis (ALS) initially revealed a duplication of exon 15 in Matrin-3 (MATR3). Whole genome sequencing determined that this genetic anomaly was, in fact, a sequence corresponding with full-length MATR3 variant 5 inserted into chromosome 12, indicating retrotransposition from a messenger RNA intermediate. To our knowledge, this is a novel mutation of MATR3, as the majority of mutations in MATR3 linked to FTD-ALS are point mutations. Genomic DNA analysis revealed that this mutation is also present in one unaffected first-degree relative and one unaffected second-degree relative. This suggests that the mutation is either a disease-causing mutation with incomplete penetrance, which has been observed in heritable FTD, or a benign variant. Retrotransposons are not often implicated in neurodegenerative diseases; thus, it is crucial to clarify the potential role of this MATR3 variant 5 retrotransposition in early-onset FTD.

Background Healthcare workers (HCWs) have suffered considerable morbidity and mortality during the COVID-19 pandemic. Few studies have evaluated Coronavac vaccine effectiveness (VE), particularly in eastern Europe, where the vaccine has been widely used. Methods We conducted a prospective cohort study among HCWs in seven hospitals in Baku, Azerbaijan between May 17 to December 1, 2021, to evaluate primary series (two-dose) CoronaVac VE against symptomatic SARS-CoV-2 infection. Participants completed weekly symptom questionnaires, provided nasal swabs for SARS-CoV-2 RT-PCR testing when symptomatic, and provided serology samples at enrolment that were tested for anti-spike and anti-nucleocapsid antibodies. We estimated VE as (1 – hazard ratio)*100 using a Cox proportional hazards model with vaccination status as a time-varying covariate. Results We enrolled 1582 HCWs. At enrolment, 1040 (66%) had received two doses of CoronaVac; 421 (27%) were unvaccinated. During the study period, 72 PCR-positive SARS-CoV-2 infections occurred; 36/39 (92%) sequenced samples were classified as delta variant. The adjusted primary series VE against COVID-19 illness was 29% (95% CI:-51%;67%). For the delta-predominant period, adjusted primary series VE was 19% (95% CI:-81%;64%). For the entire analysis period, adjusted primary series VE was 39% (95% CI:-40%;73%) for HCW vaccinated within 14–149 days, and 19% (95%CI:-81;63) for those vaccinated ≥150 days. Conclusions During a delta-predominant period in Azerbaijan, point estimates suggest that primary series CoronaVac protected nearly 1 in 3 HCWs against COVID-19, but this finding was not statistically significant. Our findings underscore the need to consider booster doses in individuals who have received primary series CoronaVac.

Background: Depression is associated with general memory impairment as well as a negativity bias, where negative experiences are better remembered. One potential mechanism underlying the negativity bias in depression could be pattern separation, a hippocampal computation that processes similar experiences as unique using non-overlapping representations, enabling individuals to remember the negative details of an experience. Mnemonic discrimination tasks, which provide a behavioral correlate of hippocampal pattern separation, have found that individuals with depressive symptoms show impaired general memory but enhanced negative mnemonic discrimination accompanied by a shift in amygdala-hippocampal dynamics (e.g. increased amygdala and reduced hippocampal activity). Antidepressants are one of the first-line treatments for depression, which have been shown to reverse hippocampal volume reduction, increase neurogenesis, and impact both memory and mood in rodent models. However, the impact of antidepressants on hippocampal pattern separation has not yet been examined in humans. Furthermore, antidepressants have limited efficacy toward successfully reducing depressive symptoms. Methods: We investigated the impact of antidepressants on memory using an emotional mnemonic discrimination task, where we previously reported a negativity bias in depression selective to mnemonic discrimination. Results: We found that individuals who reported a greater improvement in their depressive symptoms after taking antidepressants (responders) showed a reduction in the negativity bias and an enhancement in neutral mnemonic discrimination compared to those with no improvement (non-responders). Discussion: These effects were specific to mnemonic discrimination and not standard memorymeasures, suggesting that effective antidepressants can selectively enhance mnemonic discrimination and reduce the negativity bias observed in depression.

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