Cognitive impairment in Parkinson's disease (PD) has been clearly reported in the medical literature. The exact pattern of this impairment and its biomarkers are still subjects of considerable controversy. Aim: To explore the cognitive profile of patients with PD, correlate such profile with the macro and microstructural changes in the brain, evaluate the role of P300 in assessment of cognitive function in PD, and study the role of the genetic factor in the development of cognitive impairment in PD. Subjects and methods: The study was conducted on 40 patients with PD and 20 controls. Selected PD patients were submitted to evaluation of motor symptoms and psychiatric manifestations using H&Y staging and UPDRS, assessment of cognitive function using PD-Cognitive Rating Scale (PD-CRS), assessment of global brain atrophy using MRI, assessment of microstructural changes in BG, thalamus, hippocampus and prefrontal white matter using diffusion tensor imaging, measurement of P300 latency, and genotyping for GBA (L444P) mutation and BDNF (Val66Met) polymorphism. Results: The cognitive impairment in PD patients starts with executive dysfunction followed by impairment in attention, episodic memory, and visuospatial skills. Naming is the last cognitive domain to be affected in PD patients. The cognitive impairment in PD patients can’t be attributed to the genetic factor (BDNF Val66Met polymorphisms and GBA L444P mutation) only, but it depends on several other factors including: educational level, disease duration, severity of motor symptoms, tremor dominance, and psychiatric manifestations (apathy and depression). The cognitive impairment in PD patients can be attributed to macrostructural changes in the brain (global brain atrophy) and microstructural changes (decreased FA) in BG, thalamus, hippocampus and prefrontal white matter. The cognitive impairment in PD patients (impaired attention and executive dysfunction) leads to prolongation of P300 latency. Conclusion: Cognitive impairment in PD is present even in the earlier stages of the disease and it can be correlated with certain radiological, neurophysiological, and genetic biomarkers.