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As life span rises, dementia has become a growing public health issue. According to current estimates, almost 50 million people worldwide have dementia, and the number is expected to grow. Next generation sequencing (NGS) methods have helped significantly with identifying causative gene variants related to various cognitive disorders. Our study aimed to analyze the genetic basis of cognitive disorders using NGS clinical exome panel. The study included a total number of 15 unrelated cases diagnosed with cognitive disorders, all negative after standard targeted genetic testing was performed (available at Neurology Clinic, UCCS, Belgrade, Serbia). Preference was given to familial cases with early presentation or complex phenotype. Sequencing of a clinical exome (CE) panel for 4813 genes with known associated clinical phenotypes was performed using TruSight One sequencing panel on an Illumina MiSeq NGS platform according to the manufacturer's instructions (Illumina, San Diego, CA, USA). Variants were analyzed with Illumina Variant Studio v3 software provided by Illumina as well as a previously developed pipeline. Variants analysis and interpretation were based on phenotype gene target approach, literature and databases search, allele frequency, and pathogenicity prediction by in silico software. All causative variants were confirmed by Sanger sequencing. Whenever possible, additional family members were studied for segregation analysis. CE panel analysis revealed a likely genetic cause in four patients. We have detected two missense heterozygous pathogenic variants in the PSEN1 gene in one patient each and homozygous nonsense pathogenic variant in the OPTN gene in two more patients. Detected pathogenic variants are in line with the clinical phenotype of our patients. In the rest of the 11 cases, genetic diagnosis remains unclear. The results of our study emphasize the significance of CE panel analysis in establishing a diagnosis for patients with dementia. Furthermore, give us insight into the complexity of the genetic background of this group of disorders. [ABSTRACT FROM AUTHOR]