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Background Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administrated Combined Metabolic Activators (CMA) to the AD rat model and observed that administration of CMA activated the mitochondrial functions and eventually improved the AD-associated histological parameters in the animals. CMA consists of NAD + and glutathione precursors and includes L-serine, nicotinamide riboside, N-acetyl-L-cysteine, and L-carnitine tartrate. Methods Here, we designed a randomised, double-blinded, placebo-controlled phase-II trial and studied the effect of CMA administration on the global metabolism of AD patients. The primary endpoint was on the difference in cognitive and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. We also performed a comprehensive human plasma metabolome and proteome analysis. Results Based on our analysis, we showed a significant decrease of ADAS-Cog scores on Day 84 vs Day 0 (p = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant enhancement (p = 0.0073) in ADAS-Cog scores between CMA and placebo groups in patients with higher ADAS-Cog scores. Improved cognitive functions were endorsed with relevant hippocampal volumes and cortical thickness alterations. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism are significantly improved after treatment. Conclusion In conclusion, our results show that treating AD patients with CMA leads to enhanced cognitive functions associated with the improved metabolome, proteome and structural neuroimaging parameters, suggesting a role for such a therapeutic regimen in treating patients, especially with severe AD. Trial registration: ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131

The pulvinar is largest thalamic nucleus and has been subdivided into anterior pulvinar (PuA), inferior pulvinar (PuI), medial pulvinar (PuM) and, lateral pulvinar (PuL). Although the function of pulvinar is well known, its role in neurodegenerative diseases is still unclear. We aimed to examine the functional connectivity of PuA, PuI, PuM and, PuL in healthy controls (HC) and patients with Parkinson’s disease (PD). Resting-state fMRI and T1 weighted images of 15 healthy control (HC), and 12 PD patients were used in this study. SPM12 and CONN software were used to preprocessing the imaging data using published pipelines. Seed based resting-state fMRI analyses were carried out to compare the functional connectivity changes between groups. Besides, voxel-based morphometry (VBM) analysis was performed to compare gray matter volume differences between two groups. The bilateral PuI, PuL and PuM exhibited a decreased functional connectivity in the PD group compared to the HC group in the bilateral thalamus, posterior cingulate cortex, cerebellum, and brainstem. Moreover, pulvinar nuclei in each hemisphere had significantly smaller volume in the patients with PD compared to HC. This study highlights that the patients with PD have a smaller volume in pulvinar nuclei in each hemisphere compared to HC. The pulvinar showed less connectivity in the PD group compared to the HC, the diminished connectivity may be associated with hallucination, executive function, and working memory dysfunctions in PD.

Background Brain death in Turkey was defined as death and was accepted by official and religious authorities in a relatively early period without sufficient discussion and social consensus. Thus, there is considerable distrust and hesitation about the concept of brain death and related organ donation in Turkish society. We created a sample story in which the concept will be clearly understood in detail. Herein, we targeted healthcare workers and evaluated their attitudes towars brain death. Moreover, we assessed the effects of race, religiousness, and political conservatism parameters on their attitude. Methods A total of 491 participants aged 18–70 hospital workers were included to this study in different fields. The participants were asked to answer the evaluation questions about their demographic characteristics and conservative and religious attitudes. Finally, they were evaluated with an example story about brain death that was clearly understood in detail, the participants were asked to answer the questions on a 5-point Likert scale. Results We observed that 49.6% of the answers showed a positive attitude before the explanatory story. Furthermore, we observed that a higher education level is the most determining factor for positive attitudes. When the concept of death is explained within the framework of a story, only 32.1% of respondents approved of donating their organs. However, if the person consents to donate their organs with their own decision, this rate increased to 75.2% with a high rate of agreement. If the person is a close relative with a positive request for donation, the approval rate of the donation was 63.4%. We also determined that a positive attitude towards organ donation was inversely correlated with a higher education level and religiosity. Conclusion There is considerable resistance in society to consider this as a biological death, although it is recognized both by medical and religious authorities as legal. Higher education and a liberal world perspective have a positive effect on attitude, while religious belief has a negative effect. Even when the brain death concept is clearly explained and the candidate donor has a positive view of brain death and organ donation, this obstacle can be overcome to a certain degree approaching rates reported in Western countries.

Background: Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administrated Combined Metabolic Activators (CMA) to the AD rat model and observed that administration of CMA activated the mitochondrial functions and eventually improved the AD-associated histological parameters in the animals. CMA consists of NAD+ and glutathione precursors and includes L-serine, nicotinamide riboside, N-acetyl-L-cysteine, and L-carnitine tartrate. Methods: Here, we designed a randomised, double-blinded, placebo-controlled phase-II trial and studied the effect of CMA administration on the global metabolism of AD patients. The primary endpoint was on the difference in cognitive and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. We also performed a comprehensive human plasma metabolome and proteome analysis. Results: Based on our analysis, we showed a significant decrease of ADAS-Cog scores on Day 84 vs Day 0 (p=0.00001, 29% improvement) in the CMA group. Moreover, there was a significant enhancement (p=0.0073) in ADAS-Cog scores between CMA and placebo groups in patients with higher ADAS-Cog scores. Improved cognitive functions were endorsed with relevant hippocampal volumes and cortical thickness alterations. Moreover, the plasma levels of proteins and metabolites associated with NAD+ and glutathione metabolism are significantly improved after treatment. Conclusion: In conclusion, our results show that treating AD patients with CMA leads to enhanced cognitive functions associated with the improved metabolome, proteome and structural neuroimaging parameters, suggesting a role for such a therapeutic regimen in treating patients, especially with severe AD.Trial registration: ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131

Demyelination is generally observed in different neurodegenerative disorders, including Multiple sclerosis (MS). It is known that high-dose biotin supplementation stabilizes MS progression. To reduce the effective dose of biotin, here we synthesized a new and superior form of biotin, which is a complex of magnesium ionically bound to biotin (MgB) and compared its dose-dependent effect with biotin alone after lysolecithin (LPC)-induced demyelination in rats. Myelination was studied with luxol fast blue staining and revealed that the most significant remyelination occurred in the MgB groups. We observed dose-dependent improved spatial memory in both biotin and MgB combined animals. Furthermore, we detected decreased inflammatory proteins in both treatment groups, which were more prominent in high-dose MgB treated animals, associated with improved NF-κB, OP, and MMP-9 proteins. We further analyzed biotin-related proteins and observed that both biotin and particularly MgB reverses the LPC-induced reduction of these proteins. Furthermore, we have observed that biotin but particularly MgB improves neuronal transmission proteins, Synapsin-1, PSD-93, and PSD 95. Moreover, increased BDNF, GAP-43, and ICAM were detected in both treatment groups, especially significant in high-dose MgB treated animals. Increased GFAP, which indicates reactive gliosis, was observed in LPC treated animals, which were reversed particularly by high-dose MgB treatment. The present data reveal the dose-dependent beneficial effect of biotin on demyelination processes. However, a combination of biotin with Mg resulted in a more potent effect than biotin alone. The robust impact of MgB encourages proof-of-concept studies with MgB in human MS patients.