engleski

Genetic Markers in ALS Patients with Cognitive Impairment

Background: The overlap between cognitive impairment and behavioral features in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia is demonstrated in up to 50% of ALS patients. Behavioral features are mostly due to changes in serotonergic and catecholaminergic system. Objective: To identify gene polymorphisms coding for proteins involved in serotonin and catecholamine metabolism and function with the emphasis on executive function in ALS patients. Materials and methods: In a prospective study, 16 ALS patients (10 male, 60.5± 5.8 years) defined by El Escorial Criteria were investigated. Genetic markers: -1021 C/T polymorphism of DBH gene, 102 C/T polymorphism of 5-HT2A receptor gene, val158met polymorphism of COMT gene and val66met polymorphism of BDNF gene were correlated with two tests of executive functions, Controlled oral word association and Tower of London (TOL). Results: ALS patients carrying GG, GA and AA genotype of the BDNF gene polymorphism were 73%, 20% and 7%, respectively. The frequency of GG, GA, AA genotype for COMT gene polymorphism was 33%, 53% and 14%, respectively. The DBH gene polymorphism distribution was 47%, 47% and 6% for CC, CT and TT genotype, respectively. The frequency of CC, CT, TT genotype for 5-HT2A gene polymorphism was 30%, 60% and 10%, respectively. 57% of patients showed deficient word generation capability. 21% of patients were impaired on TOL Total move score and 33% of patients on TOL Total rules violation score. No significant (p>0.05) relationship between genes polymorphism and variables of executive functional tests was found. Conclusion: In this sample, we did not find correlations between gene polymorphisms and variables of executive functional tests. A sizable proportion of ALS patients’ showed behavioral and cognitive changes within a spectrum of frontotemporal impairment. Further studies on a larger sample, however, are needed in order to confirm it.

ALS ; Frontotemporal dementia ; Cognitive impairment ; Genetic markers

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