Associations of genetic variants in COMT, BDNF, SNCA, MAPT genes with cognitive impairment in Parkinson’s disease. (P6.090)

Objective: To estimate the impact of genetic variants on cognitive functions in Parkinson’s disease (PD) patients. Background: PD is a common neurodegenerative disorder that can be both sporadic and familial. Most of the PD patients eventually develop cognitive impairment, but all with a different speed. The level of impairment varies from mild cognitive impairment to dementia. Design/Methods: Cognitive examination (MMSE, MoCA tests, clock drawing test, verbal fluency test) were performed in 180 patients on the baseline and in 52 patients cognitive status was assessed prospectively with an average of 16 months on the second visit. The following SNPs Val66Met BDNF, Val158Met COMT, rs1052553 MAPT and rs2619364, rs11931074, rs2583988, rs3561168 and rs356219 SNCA were screened by PCR and restriction analysis. Results: In patients with the genotype CT/TT rs2583988 SNCA, a lower score was observed by the MMSE scale (p = 0.013), in comparison with patients with the CC genotype. In patients with the AG/GG genotype rs2619364 SNCA compare to AA genotype, a lower score of MMSE (p = 0.011) was observed. The carriers of AG/GG - rs2619364 SNCA genotype compare to carriers of AA genotype had lower speech fluency (p = 0.028). The higher MMSE score and clock drawing test were shown in carriers of genotype 66Met BDNF compared to Val/Val carriers (p=0,02) and (p = 0.016), respectively. There was no association between polymorphic variants of the COMT and MAPT genes and a decrease in cognitive function in patients with PD on the baseline. We performed prospective cognitive evaluations in 52 patients, and found decrease on MoCA scale in carriers of SNCA SNP rs2619364 genotype AA (p=0,045), rs11931074 genotype GG(p=0,041) and rs1052553 MAPT (p=0,008). Carriers of CC rs2583988 genotype have worse performance in clock drawing test (p=0,008). Conclusions: Genetic predictors of cognitive decline might serve as diagnostic biomarkers and could assist with the personification of PD treatment. Disclosure: Dr. Senkevich has nothing to disclose. Dr. Miliukhina has nothing to disclose. Dr. Shadenkov has nothing to disclose. Dr. Gracheva has nothing to disclose. Dr. Maria has nothing to disclose. Dr. Kulabukhova has nothing to disclose. Dr. Emelyanov has nothing to disclose. Dr. Pchelina has nothing to disclose.