Effect of internet-based vs. in-person multimodal interventions on patients with mild to moderate Alzheimer's disease: a randomized, cross-over, open-label trial.

Objective: We aimed to investigate the effect of internet-based and in-person cognitive interventions on cognition, mood, and activities of daily living (ADL) on patients with mild to moderate Alzheimer's disease (AD) and examine whether internet-based intervention is as effective as the in-person intervention. Methods: We recruited 52 patients with probable mild AD, of whom 42 completed the trial. We randomly divided participants into intervention and control groups at a 1:1 ratio and statistically compared the neuropsychological test results of the two groups. In addition, patients in the intervention group were randomly assigned to a 4 weeks internet-based or in-person intervention, with subsequent crossover to the other group for 4 weeks. We statistically analyzed and compared the neuropsychological test scores between internet-based and in-person interventions. Results: Compared with the control group, the intervention group (internet-based and in-person) showed significantly improved profile in cognition (p < 0.001), depression (p < 0.001), anxiety (p < 0.001) and ADL (p < 0.001). In addition, the effect of the internet-based intervention on cognition (p = 0.918) and depression (p = 0.282) was not significantly different from that of the in-person intervention. However, in the Beck anxiety inventory (p = 0.009) and Seoul instrumental activity of daily living (p = 0.023), in-person intervention was more effective than internet-based intervention. Conclusion: This study suggests that both types of cognitive intervention (in-person and internet-based) may be viable supplementary treatments along with approved pharmacological therapy. In terms of anxiety and ADL, the effect of the in-person interventions may be more effective than the-internet based interventions.

Sorting nexin 16 regulates EGF receptor trafficking by phosphatidylinositol-3-phosphate interaction with the Phox domain.

Sorting nexins (SNXs) containing the Phox (PX) domain are implicated in the regulation of membrane trafficking and sorting processes of epithelial growth factor receptor (EGFR). In this study, we investigated whether SNX16 regulates EGF-induced cell signaling by regulating EGFR trafficking. SNX16 is localized in early and recycling endosomes via its PX domain. Mutation of the PX domain disrupted the association between SNX16 and phosphatidylinositol 3-phosphate [PtdIns(3)P]. Treatment with wortmannin, a PtdIns 3-kinase inhibitor, abolished the endosomal localization of SNX16, suggesting that the intracellular localization of SNX16 is regulated by PtdIns 3-kinase activity. SNX16 was found to associate with EGFR after stimulation with EGF in COS-7 cells. Moreover, overexpression of SNX16 increased the rate of EGF-induced EGFR degradation and inhibited the EGF-induced up-regulation of ERK and serum response element (SRE). In addition, mutation in the PX domain significantly blocked the inhibitory effect of SNX16 on EGF-induced activation of ERK and SRE. From these results, we suggest that SNX16 directs the sorting of EGFR to the endosomal compartment and thus regulates EGF-induced cell signaling.