Alberto Ortega-Vázquez

Mild behavioral impairment (MBI) constitutes a late-life transition state that is associated with an increased risk of cognitive impairment and dementia. Herein, we cross-sectionally describe the MBI construct and its relationship with cognitive status in Mexican-Mestizos (MM) older adults. Participants were classified according to their cognitive and behavioral statuses using tests administered to older adults and their informants. APOE_rs429358/rs7412 variants were genotyped by real-time PCR. Multivariate correlation and Principal Components Analysis (PCA) were used in statistical analysis. A total of 246 participants were included, 56.1% were classified as individuals with NC, 13.0% had subjective cognitive decline, and 30.9% had mild cognitive impairment. A total of 37% (91/246) of participants from all over the cognitive spectrum met the MBI criteria; among this group, APOEε4 homozygosity was associated with two subdomains of the MBI. Subjective cognitive complaint, symptoms of depression, and cognitive decline reported by the informant were associated with an increased risk for MBI (ORs in the range of 4.7–15.89). The first three components of PCA explained 68.0% of the variance of the dataset, including the MBI-checklist total score as a main contributor. Well-known risk factors for dementia also correlated with this PCA. MBI could be a potential marker for cognitive decline in non-demented MM elderly people; however, observed associations should be confirmed in future longitudinal studies.

Mild Behavioral Impairment (MBI) constitutes a late-life transition state that is associated with an increased risk of cognitive impairment and dementia. Herein, we described the MBI construct and its relationship with cognitive status in Mexican-Mestizos (MM) older adults. Participants were classified according to their cognitive and behavioral statuses using tests administered to older adults and their informants. APOE_rs429358/rs7412 variants were genotyped by real-time PCR. Multivariate correlation and Principal Components Analysis (PCA) were used in statistical analysis. 246 participants were included, 13.0% had subjective cognitive decline and 30.9% mild cognitive impairment. 37% (91/246) of participants from all the cognitive spectrum met the MBI criteria; among this group, being carrier of APOEε4 was associated with two subdomains of the MBI. Subjective cognitive complaint, symptoms of depression and cognitive decline reported by the informant were associated with an increased risk for MBI (ORs in the range of 4.7-15.89). The first three components of PCA explained 68.0% of the variance of the data set, including MBI-checklist total score as a main contributor. Well-known risk factors for dementia also correlated with this PCA. MBI could be a relevant marker for cognitive decline in non-demented MM elderly people.

Background/Objective: Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, in which the inflammatory hypothesis posits that dysregulation of the immune system is an important factor in its etiology. Based on our previous findings, we aimed to explore if promoter functional genetic variants in cytokines encoded by IL-10 and IL-17A, and a coding variant in the IL-13 gene, confer risk to the inflammatory profile of PD patients. Methods: For population genetic purposes, DNA samples from 239 patients with sporadic PD and 84 healthy controls were included and genotyped for IL-10_rs1800896, IL-10_rs1800872, IL-13_rs20541, IL-17A_rs2275913, and IL-17_rs8193036 variants by allelic discrimination in real-time PCR. All participants were Mexican Mestizos (MMs). Gene frequencies and haplotype association analyses were assessed. Then, a subgroup of 26 untreated PD patients and 21 controls were selected from this cohort for detailed biochemical and clinical data and evaluated by multivariate correlation analysis at the baseline and one year post-dopaminergic replacement treatment. Results and Conclusions: IL-17A_rs8193036 was found to be associated with increased PD risk (p < 0.010, OR = 1.91, CI_95% = 1.22–2.98). The genetic variants IL-10_rs1800896, IL-10_rs1800872, and IL_17A_rs8193036 were related to the inflammatory process in sporadic MM PD patients, suggesting that they may play potential roles in the development and severity of the disease.

Background/Objectives: Antiseizure drugs (ASDs) are the primary therapy for epilepsy, and the choice varies according to seizure type. Epilepsy patients experience chronic mitochondrial oxidative stress and increased levels of pro-inflammatory mediators, recognizable hallmarks of biological aging; however, few studies have explored aging markers in epilepsy. Herein, we addressed for the first time the impact of ASDs on molecular aging by measuring the telomere length (TL) and mtDNA copy number (mtDNA-CN). Methods: We used real-time quantitative PCR (QPCR) in epilepsy patients compared to matched healthy controls (CTs) and assessed the association with plasma levels of ASDs and other clinical variables. The sample comprised 64 epilepsy patients and 64 CTs. Patients were grouped based on monotherapy with lamotrigine (LTG) or valproic acid (VPA), and those treated with a combination therapy (LTG + VPA). Multivariable logistic regression was applied to analyze the obtained data. Results: mtDNA-CN was similar between patients and controls, and none of the comparisons were significant for this marker. TL was shorter in not seizure-free patients than in CTs (1.50 ± 0.35 vs. 1.68 ± 0.34; p < 0.05), regardless of the ASD therapy. These patients exhibited the highest proportion of adverse drug reactions. TL was longer in patients on VPA monotherapy, followed by patients on LTG monotherapy and patients on an LTG + VPA combined scheme (1.77 ± 0.24; 1.50 ± 0.32; 1.36 ± 0.37, respectively; p < 0.05), suggesting that ASD treatment differentially modulates TL. Conclusions: Our findings suggest that clinicians could consider TL measurements to decide the best ASD treatment option (VPA and/or LTG) to help predict ASD responses in epilepsy patients.

Background/Objectives: Antiseizure drugs (ASDs) are the primary therapy for epilepsy and the choice varies according to the seizure type. Epilepsy patients experience chronic mitochondrial oxidative stress and increased levels of pro-inflammatory mediators, recognizable hallmarks of biological aging, however few studies have explored aging markers in epilepsy. Herein, we addressed for the first time the impact of ASDs on molecular aging by measuring telomere length (TL) and mtDNA copy number (mtDNA-CN). Methods: Using QPCR, in epilepsy patients compared to matched healthy controls (CT), and its association with plasma levels of ASDs and other clinical variables. The sample comprised 64 epilepsy patients and 64 CT. Patients were grouped on monotherapy with lamotrigine (LTG) or valproic acid (VPA), and those treated with a combination therapy (LTG+VPA). Multivariable logistic regression was applied to analyze obtained data. Results: mtDNA-CN was similar between patients and controls, and none of the comparisons were significant for this marker. TL was shorter in not seizure-free patients than CT (1.50±0.35 vs. 1.68±0.34, p<0.05), regardless of the ASD therapy. These patients exhibited the highest proportion of adverse drug reactions. TL was longer in patients on VPA monotherapy, followed by patients on LTG monotherapy and by patients on LTG+VPA combined scheme (1.77±0.24; 1.50±0.32; 1.36±0.37 respectively, p<0.05), suggesting that ASD treatment differentially modulates TL. Conclusions: Our findings suggest that clinicians could consider TL measurements to decide the best ASD treatment option (VPA and/or LTG) to help predict ASD response in epilepsy patients.

Parkinson’s disease (PD) pathophysiology includes mitochondrial dysfunction, neuroinflammation, and aging as its biggest risk factors. Mitochondrial DNA copy number (mtDNA-CN) and telomere length (TL) are biological aging markers with inconclusive results regarding their association with PD. A case–control study was used to measure TL and mtDNA-CN using qPCR in PBMCs. PD patients were naive at baseline (T0) and followed-up at one (T1) and two (T2) years after the dopaminergic treatment (DRT). Plasmatic cytokines were determined by ELISA in all participants, along with clinical parameters of patients at T0. While TL was shorter in patients vs. controls at all time points evaluated (p < 0.01), mtDNA-CN showed no differences. An increase in mtDNA-CN and TL was observed in treated patients vs. naive ones (p < 0.001). Our statistical model analyzed both aging markers with covariates, showing a strong correlation between them (r = 0.57, p < 0.01), and IL-17A levels positively correlating with mtDNA-CN only in untreated patients (r = 0.45, p < 0.05). TL and mtDNA-CN could be useful markers for monitoring inflammation progression or treatment response in PD. DRT might modulate TL and mtDNA-CN, reflecting a compensatory mechanism to counteract mitochondrial dysfunction in PD, but this needs further investigation.

Alzheimer’s disease (AD) is characterized by the presence of neuropsychiatric or behavioral and psychological symptoms of dementia (BPSD). BPSD have been associated with the APOE_ε4 allele, which is also the major genetic AD risk factor. Although the involvement of some circadian genes and orexin receptors in sleep and behavioral disorders has been studied in some psychiatric pathologies, including AD, there are no studies considering gene–gene interactions. The associations of one variant in PER2, two in PER3, two in OX2R and two in APOE were evaluated in 31 AD patients and 31 cognitively healthy subjects. Genotyping was performed using real-time PCR and capillary electrophoresis from blood samples. The allelic-genotypic frequencies of variants were calculated for the sample study. We explored associations between allelic variants with BPSD in AD patients based on the NPI, PHQ-9 and sleeping disorders questionnaires. Our results showed that the APOE_ε4 allele is an AD risk variant (p = 0.03). The remaining genetic variants did not reveal significant differences between patients and controls. The PER3_rs228697 variant showed a nine-fold increased risk for circadian rhythm sleep–wake disorders in Mexican AD patients, and our gene–gene interaction analysis identified a novel interaction between PERIOD and APOE gene variants. These findings need to be further confirmed in larger samples.

Objective: The clinical trajectories of patients with psychotic disorders have divergent outcomes, which may result in part from glutathione (GSH)-related high-risk genotypes. We aimed to determine pharmacokinetics of clozapine, GSH levels, GSH peroxidase (GPx) activity, gene variants involved in the synthesis and metabolism of GSH, and their association with psychotic disorders in Mexican patients on clozapine monotherapy and controls. Methods: The sample included 75 patients with psychotic disorders on clozapine therapy and 40 paired healthy controls. Plasma clozapine/N-desmethylclozapine, GSH concentrations, and GPx activity were determined, along with genotyping of GCLC and GSTP1 variants and copy number variations of GSTP1, GSTT1, and GSTM1. Clinical, molecular and biochemical data were analyzed with a logistic regression model. Results: GSH levels were significantly reduced and, conversely, GPx activity was higher among patients than controls. GCLC_GAG-7/9 genotype (OR = 4.3, 95 degrees/0CI = 1.40-14.31, p = 0.019) and hetero-/homozygous genotypes of GCLC_rs761142 (OR = 6.09, 95 degrees/0CI = 1.93-22.59, p = 0.003) were found to be risk factors for psychosis. The genetic variants were not related to clozapine/Ndesmethylclozapine levels or metabolic ratio. Conclusions: GCLC variants were associated with the oxidative stress profile of patients with psychotic disorders, raising opportunities for intervention to improve their antioxidant defenses. Further studies with larger samples should explore this proposal.

Clozapine (CLZ) is an atypical antipsychotic reserved for patients with refractory psychosis, but it is associated with a significant risk of severe adverse reactions (ADRs) that are potentiated wi...

Aim: We evaluated the potential influence of genetic (CYP3A5, EPHX1, NR1I2, HNF4A, ABCC2, RALBP1, SCN1A, SCN2A and GABRA1) and nongenetic factors on carbamazepine (CBZ) response, adverse drug react...