In amnestic mild cognitive impairment (aMCI), neuroinflammation evolves during disease progression, affecting microglial function and potentially accelerating the pathological process. Currently, no effective treatment exists, leading to explorations of various symptomatic approaches, though few target the underlying physiological mechanisms. Modulating inflammatory processes may be critical in slowing disease progression. Cognitive stimulation (CS) and transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex (l-DLPFC) show promise, but the results are heterogeneous. Thus, a randomized, double-blind, placebo-controlled clinical trial is currently underway. The first-stage results were examined after three weeks of intervention in two groups: active tDCS combined with CS and sham tDCS combined with CS. Twenty-two participants underwent two assessments: T0 (baseline) and T1 (after 15 sessions of tDCS, active or sham, and 9 sessions of CS). The results demonstrated that CS improved cognition, increased brain-derived neurotrophic factor (BDNF) levels, and reduced peripheral proinflammatory cytokine levels (interleukin IL-6 and chemokine CX3CL1) in serum. This decrease in IL-6 may promote microglial proliferation and survival as a modulatory effect response, while the increase in BDNF might suggest a regulatory mechanism in microglia–neuron interaction responses. However, tDCS did not enhance the cognitive or modulatory effects of CS, suggesting that longer interventions might be required to achieve substantial benefits.

BACKGROUND: Cocaine use disorder (CUD) is a global condition lacking effective treatment. Repeated magnetic transcranial stimulation (rTMS) may reduce craving and frequency of cocaine use, but little is known about its efficacy and neural effects. METHODS: Using a double-blind placebo-controlled randomized clinical trial (RCT) [ NCT02986438 ], we sought to elucidate short- and long-term clinical benefits of 5-Hz rTMS as an add-on to standard treatment in CUD patients and discern underlying functional connectivity effects using magnetic resonance imaging. Forty-four randomly assigned CUD patients completed the 2-week double-blind acute phase [Sham (n=20, 2f/18m) and Active (n=24, 4f/20m)], in which they received 2 daily sessions of rTMS (5,000 pulses) on the left dorsolateral prefrontal cortex. Subsequently, n=20 CUD patients continued to open-label maintenance (2 weekly sessions for up to 6 months). Measures were acquired at baseline, 2 weeks, 3 months and 6 months. RESULTS: Overall, 5-Hz rTMS plus standard treatment for 2 weeks significantly reduced craving and impulsivity in the Active group; decreased impulsivity correlated with improvements in functional connectivity in executive control and default mode networks. Clinical and functional connectivity effects were maintained for 3 months but they dissipated by 6 months. We did not observe reduction of positive cocaine urine tests, however, self-reported frequency and grams consumed for 6 months were reduced. CONCLUSIONS: With this RCT we show that 5-Hz rTMS has potential promise as an adjunctive treatment for CUD and merits further research.

Brackground: Current treatments for Alzheimer’s disease (AD) have a limited clinical response and methods, such as repetitive transcranial magnetic stimulation (rTMS), are being studied as possible treatments for the clinical symptoms with positive results. However, there is still seldom information on the type of rTMS protocols that deliver the best clinical improvement in AD. Objetive: To compare the clinical response between a simple stimulation protocol on the left dorsolateral prefrontal cortex (lDLPFC) against a complex protocol using six regions of interest. Methods: 19 participants were randomized to receive any of the protocols. The analysis of repeated measures evaluated the change. Results: Both protocols were equally proficient at improving cognitive function, behavior and functionality after 3 weeks of treatment, and the effects were maintained for 4 weeks more without treatment. Conclusion: We suggest rTMS on the lDLPFC could be enough to provide a clinical response, and the underlying mechanisms should be studied.

Cocaine use disorder (CUD) presents high comorbidity with mood symptoms that impair recovery processes and facilitate relapses. Peripheral brain-derived neurotrophic factor (BDNF) is negatively correlated with mood symptoms in depressive disorders. However, whether a correlation exists between BDNF and mood in CUD is still unknown. Thus, in this cross-sectional study, we explored the potential relationship between peripheral BDNF levels and depression and anxiety symptoms in CUD. Serum peripheral BDNF was determined by the ELISA method. Standardized Hamilton Depression (HDRS) and Anxiety (HARS) inventories were administered. Twenty-nine seeking-treatment CUD participants under stable medication (female = 3) were enrolled. According to the mood severity, 34.48% of participants were classified as normal, 24.14% as moderate, and 41.38% as severe symptoms (p < 0.001). Peripheral BDNF was similar between the different mood severity groups (p > 0.05). No correlation between BDNF and HDRS and BDNF and HARS was detected regardless of the severity of mood symptoms (p > 0.05). Different from what has been observed in depressive disorders, independence between peripheral BDNF levels and mood symptoms in CUD was observed. This finding suggests a singular, intricate regulation of peripheral BDNF and mood as part of CUD-related maladaptations that might disrupt the expected antidepressant response and perpetuate mood symptoms in CUD.