Association between ABCB1 polymorphisms and response to first-generation antiepileptic drugs in a Tunisian epileptic population.

PURPOSE: We aimed in this study to investigate the association between the ATP-Binding Cassette sub-family B, member1 (ABCB1) polymorphisms: C1236T (rs1128503), G2677T (rs2032582) and C3435T (rs1045642), and the resistance to antiepileptic drugs (AEDs). MATERIALS AND METHODS: The Polymerase Chain Reaction-Restriction Fragment Length Polymorphism genotyping of ABCB1 polymorphisms was conducted on 153 Tunisian epileptic patients treated with AEDs. RESULTS: Two genetic polymorphisms of the ABCB1 gene seemed to influence the response to AEDs. In fact, the G2677T T and the C3435T T alleles appeared to increase the risk of developing AEDs resistance (ORs* = 3.13; 95%CI = [1.16-8.98]; p = 0.024 and ORs* = 3.10; 95%CI = [1.15-8.37]; p = 0.025), respectively. However, the C1236T T allele did not seemed to influence the response to AEDs (ORs* = 1.14; 95%CI = [0.53-3.88]; p = 0.471). Haplotypic analysis indicated high-degree linkage disequilibrium of ABCB1 polymorphisms. Our results showed a synergic effect, in fact patients with the CTT and TTT haplotypes were more likely to be drug resistant than patients with the CGC haplotype, these associations remained significant even after adjustment for confounding parameters (ORs* = 2.68; 95%CI = [1.11-8.25]; p = 0.033 and ORs* = 3.76; 95%CI = [1.69-21.05]; p = 0.006, respectively). CONCLUSION: The G2677T T and C3435T T alleles as well as the TT, CTT and TTT haplotypes seemed to be significantly associated with drug-resistance epilepsy in our population. Genetic predisposition, involved in this resistance, may contribute to the establishment of a personal optimized therapy for newly diagnosed epileptic patients.

Acute Effect of Simultaneous Exercise and Cognitive Tasks on Cognitive Functions in Elderly Individuals with Mild Cognitive Impairment.

The increasing prevalence of age-related cognitive decline, alongside the aging global population, underscores the urgent need for innovative and effective preventative strategies. While the advantages of combining physical and cognitive exercises have been recognized as a promising approach to address these socioeconomic challenges, the acute effects of such interventions on cognitive functions remain understudied. This study aimed to investigate whether simultaneous physical and cognitive exercise has a greater beneficial impact on the cognitive functions of older adults with mild cognitive impairment (MCI) than physical exercise alone or reading activities. A total of 44 MCI patients (75% females aged between 65 and 75 years) were randomly assigned to one of three groups: aerobic exercise alone (EG group, n = 15), aerobic combined with cognitive exercises (CEG group, n = 15), or a reading task for controls (CG group, n = 14). Attention, memory, and problem solving were assessed before and after the acute intervention using the Tower of Hanoi, Digit Span, and Stroop tasks, respectively. Statistical analysis revealed that both of the experimental interventions appeared to enhance cognitive function scores (p < 0.05), except for the number of moves in the Tower of Hanoi task, where no improvement was noted. In contrast, no significant differences in any cognitive performance measures were observed following the reading session. Notably, the CEG group exhibited a more pronounced positive impact, especially on working memory. This advantage was specifically evident in the digit span tasks, where significantly greater percentage gains were found in the CEG than in the CG (p = 0.02), while no significant difference existed between the EG and CG. Simultaneous combined exercise has proven to be a more effective method than aerobic physical exercise alone for improving cognitive function. The results of this study are recommended for inclusion in clinical practice guidelines to maintain the mental health of older adults, as simultaneous exercise seems to offer a time-efficient strategy to enhance cognitive performance in adults with MCI.

The relationship between pharmacokinetic parameters of carbamazepine and therapeutic response in epileptic patients.

INTRODUCTION: The prescribed dose and carbamazepine plasma concentration to achieve the optimal therapeutic efficacy are highly variable from one patient to the other. Our study aimed to determine whether biological parameters may be used as plasma markers that can individually adjust the carbamazepine dose necessary to optimize therapeutic efficacy. MATERIAL AND METHODS: Ninety-four epileptic patients under carbamazepine monotherapy and who have never used combination therapy were recruited from the consecutive admissions at the Department of Neurology "CHU Sahloul" of Sousse Central Hospital in Tunisia from February 2010 to April 2011. The patients were monitored for epilepsy for three years on average. Carbamazepine and 10,11-epoxide-carbamazepine concentrations were analyzed through high-performance liquid chromatography. Simultaneously, therapeutic efficacy was assessed through the annual number of seizures in each patient. RESULTS: Our results showed the absence of any significant correlations between specific dose (mg/kg/day), carbamazepine plasma concentrations and therapeutic efficacy (r = 0.0025, p = 0.30; r = 0.1584, p = 0.38 respectively), whereas both plasma 10,11-epoxide-carbamazepine concentration and 10,11-epoxide-carbamazepine to plasma carbamazepine ratio were closely correlated with therapeutic efficacy (r = 0.34, p = 0.03; r = 0.45, p = 0.008 respectively). The optimum therapeutic response was observed among patients who simultaneously had a plasma concentration of 0.8 µg/ml of metabolite and 5.5 µg/ml of carbamazepine. CONCLUSIONS: The results suggest that plasma levels of both carbamazepine and of 10,11-epoxide-carbamazepine must be set to achieve an optimum therapeutic response.