RESUMEN
Just as its clinical heterogeneity, genetic basis of Frontotemporal dementia (FTD) is also diverse and multiple molecular pathways are thought to be involved in disease pathogenesis. In the present study, FTD- related genes were evaluated in a Turkish cohort of 175 index FTD patients with a gene panel including GRN, MAPT, TARDBP, FUS, CHMP2B and VCP genes. Potential genetic associations were prospected in 16 patients (9.1%); five variants (p.(Gly35Glufs) and p.(Cys253Ter) in GRN; p.(Arg95Cys) in VCP; p.(Met405Val) in TARDBP and p.(Pro636Leu) in MAPT) were classified as pathogenic (P) or likely pathogenic (LP), in four familial and one sporadic patients. Three novel variants in MAPT, CHMP2B and FUS were also identified in familial cases. The most common pathogenic variants were observed in the GRN gene with a frequency of 1.14% (2/175) and this rate was 4.57% (8/175), including variants of uncertain significance (VUS). In this study with the largest cohort of Turkish FTD patients, GRN and MAPT variants were identified as the most common genetic associations; and rare causes like VCP, TARDBP, CHMP2B and FUS variants are recommended to be considered in patients with compatible clinical findings.
Asunto(s)
Demencia Frontotemporal/epidemiología , Demencia Frontotemporal/genética , Frecuencia de los Genes/genética , Estudios de Asociación Genética/métodos , Variación Genética/genética , Progranulinas/genética , Proteínas tau/genética , Anciano , Estudios de Cohortes , Proteínas de Unión al ADN/genética , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Persona de Mediana Edad , Proteína FUS de Unión a ARN/genética , Turquía/epidemiología , Proteína que Contiene Valosina/genéticaRESUMEN
Objective This study was performed to assess the efficacy of memantine in patients with amnestic mild cognitive impairment (aMCI). Methods Thirty healthy controls and 45 patients diagnosed with aMCI based on the Petersen criteria were classified into 3 groups. Group 1 comprised patients who received a single memantine dose following examination (n = 25), Group 2 comprised patients who did not receive memantine treatment following examination (n = 20), and Group 3 comprised healthy age-matched volunteers (n = 30). Neuropsychological testing was performed, and the response to memantine was examined at baseline and at 12, 24, and 48 weeks. Single-photon emission computed tomography was performed at baseline and at 48 weeks in patients who received memantine treatment. Results Memantine treatment significantly improved the symptoms of aMCI according to the Wechsler Adult Intelligence Scale-Revised vocabulary subtest, backward digit span, and Blessed Dementia Rating Scale, all of which were recorded for the duration of the study. Conclusion These data indicate that patients with aMCI receiving memantine develop an improved semantic memory compared with no treatment. Further studies including larger patient cohorts are necessary to validate these findings.
