Effects of bilateral transcranial direct current stimulation on working memory and global cognition in older patients with remitted major depression: A pilot randomized clinical trial.

OBJECTIVES: To assess the effects of a 10-day course of bilateral anodal transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) on working memory and global cognition in elderly participants with remitted major depressive disorder at 14 days (primary outcome) and 90 days (secondary outcome) post intervention. DESIGN: Randomized double blind controlled trial (clinicaltrials.gov # NCT02212366). SETTING: Community dwelling outpatient setting. PARTICIPANTS: Sixty or older with previous single or recurrent episodes of major depression currently in full remission. INTERVENTION: A 10 day course of active or sham bilateral DLPFC anodal tDCS. MEASUREMENTS: (a) Working memory assessed by a computerized N back task, and (b) global cognition assessed by a standard paper and pencil neuropsychological test battery. RESULTS: Thirty-three participants, (mean (SD) age = 66. 5 (5.7) year) were enrolled, out of which 18 (mean (SD) age = 66. 3 (5.8) year) were randomized to active tDCS and 15 (mean (SD) age = 66. 7 (5.8) years) to sham tDCS. All randomized participants except one from the sham group -completed the tDCS course. There were no differences between the groups on working memory performance or global cognition at 14 or 90 days post intervention. Both groups showed promising changes in working memory and global cognition over time. CONCLUSIONS: tDCS was well tolerated in older patients with remitted MDD, however, as compared to the sham group, it did not improve working memory or global cognition. Future studies should investigate tDCS with alternative parameters to enhance cognition in this population.

Innate and Adaptive Immune Correlates of Chronic and Self-limiting EBV DNAemia in Solid-organ Transplant Recipients.

BACKGROUND: Epstein-Barr virus (EBV) DNAemia is a major risk factor for posttransplant lymphoproliferative disorder; however, immune correlates of EBV DNAemia in the transplant setting are limited. METHODS: Peripheral blood mononuclear cells were collected from 30 transplant recipients with self-limiting EBV DNAemia (SLD; n = 11) or chronic EBV DNAemia (CD; n = 19) at enrollment and 4-8 weeks later. Mass cytometry was used to characterize innate and T-cell immune correlates of EBV DNAemia. Furthermore, flow cytometry was used to measure the frequency of EBV-specific T-cell responses between groups following stimulation with an EBV-infected cell lysate. RESULTS: Unsupervised analysis of the innate compartment (CD3CD19 cells) identified 5 CD11c clusters at higher abundance in the SLD group (false discovery rate ≤ 1%). These clusters expressed CD11b, CD45RO, CD14, CD123, CD127, and CD38, among others. Unsupervised profiling of the T-cell compartment (CD3CD19) revealed 2 CD4 T-cell clusters at higher frequency among those with SLD (false discovery rate ≤ 1%), which expressed CD45RA, CCR7, CD27, CD28, and CD40L-suggestive of a naive T cell (TN). Manual biaxial gating confirmed increased frequencies of conventional dendritic cells (3.1% versus 2.1%; P = 0.023) and CD4 TN (4.4% versus 1.9%; P = 0.018) among those with SLD. Last, frequencies of interferon-γ-producing EBV-specific CD4 T cells were significantly lower in the CD group relative to those with SLD (4243 versus 250 cells/10 cells; P = 0.015). CONCLUSIONS: CD is associated with a reduction of CD11c cells, CD4 TN, and interferon-γ-producing EBV-specific CD4 T cells, suggesting an interplay between innate and adaptive immune compartments may be important for regulating EBV DNAemia.