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.

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.

A simple and rapid UV derivative method with zero-crossing determinations was developed for estimation of acetaminophen (ACE) and caffeine (CAF) in fixed-dose combination formulations. The first-derivative of standard solutions of both drugs were used and ACE and CAF were quantified at 273.0 and 216.5 nm, respectively. The method was validated, and it was applied to dissolution studies with the USP Apparatus 2 and flow-through cell (USP Apparatus 4). Dissolution profiles comparisons (generic vs reference) were carried out with model-independent and model-dependent approaches. Mean dissolution time and dissolution efficiency were calculated and significant differences, in almost all calculated parameters, were found (p<0.05). Weibull, logistic, Gompertz, and Probit models were used to fit dissolution data and Probit was the best-fit model that describes the in vitro dissolution performance of ACE and CAF. Using t50% data, derived from this fit, dissolution profiles of ACE in USP Apparatus 2 were significant different (p<0.05). The proposed UV derivative method generates reliable information that can be compared with published results. Dissolution studies of fixed-dose combination formulations are important because quality of generic drug products depends on quality of references. It is essential to maintain a post-marketing evaluation of formulations with analgesic drugs mixed with CAF to offer the population high quality medicines.

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.

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.