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Introduction: Mild cognitive impairment (MCI) can progress to Alzheimer's disease (AD). When MCI is not properly controlled, the speed of deterioration can dramatically increase. Reduction of oxidative stress/inflammation and the modulation of the gut-brain axis could be new potential therapeutic targets for the prevention and treatment of AD. Consumption of specific nutrients, diets and probiotic supplementation have been evaluated for neurodegenerative disorders. We focus on a detailed description of the study methods and baseline characteristics of a clinical trial aiming to evaluate the efficacy of a combined nutritional intervention, i.e., a Mediterranean diet with probiotics, on cognitive capacity in a population with MCI., Methods: In this randomized, latin-square crossover, double-blind, and controlled dietary intervention trial (clinicaltrials.gov NCT05029765), 47 MCI patients were randomized to consume three dietary interventions for 24-weeks each: (1) A Mediterranean diet supplemented with probiotics (10 9 colony-forming units of Lactobacillus rhamnosus and Bifidobacterium longum ); (2) A Mediterranean diet + placebo; and (3) A Healthy diet according to the World Health Organization (WHO) recommendations. Participants will be evaluated before and after each of the three intervention periods (each 24-weeks, with a total of 72-weeks) for adherence to the assigned diet, blood tests, cognitive performance, gut microbiota analysis and functional neuroimaging studies., Results: Fifty patients, ≥60 years-old and diagnosed with MCI, underwent randomization. A total of 47 patients completed follow-up dietary interventions (57.4% males), with a good glycemic control (HbA1c 5.8 ± 0.1%, fasting glucose and insulin 99.7 ± 3.3 mg/dL and 10.4 ± 0.9 mU/L, respectively), elevated systolic blood pressure (136.9 ± 2.1 mmHg) and increased degree of inflammation (high-sensitivity C-reactive protein, 8.8 ± 0.9 mg/dL). Baseline adherence to the Mediterranean diet was medium (7.5 ± 0.3 points on the score that ranged from 0 to 14 points)., Conclusion: The results of this clinical study would provide more evidence on the need for dietary therapeutic strategies, for clinical and individual practice, in the management of MCI patients to reduce the risk of AD development. Targeting lifestyle modifications in high-risk populations could prevent substantial cases of cognitive decline., Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT05029765]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cardelo, Corina, Leon-Acuña, Quintana-Navarro, Alcala-Diaz, Rangel-Zuñiga, Camargo, Conde-Gavilan, Carmona-Medialdea, Vallejo-Casas, Carmona-Asenjo, Ochoa-Sepulveda, Aguera-Morales, Delgado-Lista, Katsiki, Lopez-Miranda, Perez-Jimenez, Yubero-Serrano and Perez-Martínez.)

Objective: We aimed to investigate the prevalence of TOR1A, GNAL and THAP1 variants as the cause of dystonia in a cohort of Spanish patients with isolated dystonia and in the literature., Methods: A population of 2028 subjects (including 1053 patients with different subtypes of isolated dystonia and 975 healthy controls) from southern and central Spain was included. The genes TOR1A, THAP1 and GNAL were screened using a combination of high-resolution melting analysis and direct DNA resequencing. In addition, an extensive literature search to identify original articles (published before 10 August 2020) reporting mutations in TOR1A, THAP1 or GNAL associated to dystonia was performed., Results: Pathogenic or likely pathogenic variants in TOR1A, THAP1 and GNAL were identified in 0.48%, 0.57% and 0.29% of our patients, respectively. Five patients carried the variation p.Glu303del in TOR1A. A very rare variant in GNAL (p.Ser238Asn) was found as a putative risk factor for dystonia. In the literature, variations in TOR1A, THAP1 and GNAL accounted for about 6%, 1.8% and 1.1% of published dystonia patients, respectively., Conclusions: There is a different genetic contribution to dystonia of these three genes in our patients (about 1.3% of patients) and in the literature (about 3.6% of patients), probably due the high proportion of adult-onset cases in our cohort. As regards age at onset, site of dystonia onset, and final distribution, in our population there is a clear differentiation between DYT-TOR1A and DYT-GNAL, with DYT-THAP1 likely to be an intermediate phenotype., (© 2020 European Academy of Neurology.)

Background: A recent genome-wide association study (GWAS) has identified a putative association, not statistically confirmed, of cervical dystonia within several regions in a British population. Hence, the authors proposed dysfunction of the ion channel NALCN (for sodium leak channel, nonselective) as a plausible cause of cervical dystonia. The objective of our study was to investigate the association of five single nucleotide polymorphisms (SNPs) previously reported with high signals as putative genetic risk factors for cervical dystonia in a British GWAS, including two located in the NALCN gene region., Methods: We performed a case-control association study in a Spanish population. The SNPs selected for genotyping were two SNPS in the NALCN gene (rs61973742 and rs1338041), one SNP in the OR4X2 gene (rs67863238), one SNP in the COL4A1 region (rs619152), and one intergenic SNP (rs1249277). Genomic DNA was collected from 252 patients with cervical dystonia, with a mean age of 55.3 ± 14.1 years (mean age at onset, 43.5 ± 15.7 years), and 342 unrelated control subjects with a mean age of 56.3 ± 14.3 years. Genotyping of SNPs was performed using TaqMan assays and SimpleProbe assays., Results: The SNP rs619152 had to be excluded because of assay failure. No significant differences were found in allele distribution between cases and controls for all analyzed SNPs. Therefore, we found no association with cervical dystonia for the analyzed SNPs in our Spanish population., Conclusions: We did not find any evidence supporting the association of NALCN with cervical dystonia, indicating that this gene is not implicated in the pathogenesis of this disorder in our cervical dystonia population., (© 2014 International Parkinson and Movement Disorder Society.)