A relationship between delirium with APOE genotype, IFN-gamma, and IGF-I, but not with IL-6, IL-1, TNF-alpha, and LIF was found. A predictive model of recovery was derived from gender, APOE status, and IGF-I levels. This model needs replication with further studies.

this study finds that (i) low levels of both neuroprotective factors (IGF-I, IL-1RA) are associated with delirium, (ii) high IFN-gamma and low IGF-I have significant effects on delirium severity and (iii) otherwise the pro-inflammatory cytokines studied, APOE genotype and severity of illness do not appear to be associated, in older medically ill patients, with either delirium or severity of it.

BackgroundAgitation in Alzheimer’s disease (AD) is common and associated with poor patient life-quality and carer distress. The best evidence-based pharmacological treatments are antipsychotics which have limited benefits with increased morbidity and mortality. There are no memantine trials in clinically significant agitation but post-hoc analyses in other populations found reduced agitation. We tested the primary hypothesis, memantine is superior to placebo for clinically significant agitation, in patients with moderate-to-severe AD.Methods and FindingsWe recruited 153 participants with AD and clinically significant agitation from care-homes or hospitals for a double-blind randomised-controlled trial and 149 people started the trial of memantine versus placebo. The primary outcome was 6 weeks mixed model autoregressive analysis of Cohen-Mansfield Agitation Inventory (CMAI). Secondary outcomes were: 12 weeks CMAI; 6 and 12 weeks Neuropsychiatric symptoms (NPI), Clinical Global Impression Change (CGI-C), Standardised Mini Mental State Examination, Severe Impairment Battery. Using a mixed effects model we found no significant differences in the primary outcome, 6 weeks CMAI, between memantine and placebo (memantine lower −3.0; −8.3 to 2.2, p = 0.26); or 12 weeks CMAI; or CGI-C or adverse events at 6 or 12 weeks. NPI mean difference favoured memantine at weeks 6 (−6.9; −12.2 to −1.6; p = 0.012) and 12 (−9.6; −15.0 to −4.3 p = 0.0005). Memantine was significantly better than placebo for cognition. The main study limitation is that it still remains to be determined whether memantine has a role in milder agitation in AD.ConclusionsMemantine did not improve significant agitation in people with in moderate-to-severe AD. Future studies are urgently needed to test other pharmacological candidates in this group and memantine for neuropsychiatric symptoms.Trial RegistrationClinicalTrials.gov NCT00371059 Trial RegistrationInternational Standard Randomised Controlled Trial 24953404

Muc1 is a heterodimeric mucin that is expressed on the apical surface of airway epithelial cells as well as hematopoietic cells. Both in vivo and in vitro studies revealed that Muc1 suppresses inflammatory responses induced by Pseudomonas aeruginosa (PA). In this study, we sought to determine, using intact animals (C57BL/6 mice), whether the expression of Muc1 is important during airway PA infection, and how Muc1 levels are controlled during inflammation. Our results showed that: (1) Muc1 levels in the wild-type (WT) mice were initially low, but gradually increased after PA inhalation, reaching a peak on Day 2, remaining elevated until Day 4, and then gradually decreasing to basal levels on Day 7; (2) TNF receptor 1(-/-) mice failed to increase Muc1 levels after PA infection; (3) after PA inhalation, more inflammatory cells were present in the bronchoalveolar lavage fluid from either Muc1(-/-) or TNF receptor(-/-) mice compared with their WT control animals; (4) more apoptotic neutrophils were present in bronchoalveolar lavage fluid from WT mice compared with Muc1(-/-) mice. We conclude that Muc1(-/-) mice are more inflammatory than WT mice during airway PA infection as a result of both an increase in neutrophil influx and a decrease in neutrophil apoptosis. These results suggest that the up-regulation of Muc1 during airway PA infection might be crucial for suppressing excessive and prolonged inflammatory responses, and is induced mainly by TNF-α, the key proinflammatory mediator.