- Email: [email protected]
CYP2D6 and catechol-O-methyltransferase gene polymorphisms in Parkinson patients with levodopa-induced dyskinesias
S656
P.5.d. Dementia and neurological disorders − Neurological disorders (clinical)
observed for 3 days without medication, non-dementia patients with postsurgical delirium with old lacunar infarct sequelae in the right thalamus had more severe delirium than non-dementia patients without old lacunar infarct sequelae in the right thalamus. Early, effective treatment of these patients should have a positive impact on postsurgical delirium. Our study supports the hypothesis that structural dysconnectivity involving the interhemispheric and fronto-thalamo-cerebellar networks predisposes to delirium under the stress of surgery [2]. The right thalamus may also play a significant role in aggravating postsurgical delirium. Further studies are needed to research the role of the left thalamus for postsurgical delirium in non-dementia patients. References [1] Shioiri, A., Kurumaji, A., Takeuchi, T., Matsuda, H., Arai, H., Nishikawa, T., 2010. White matter abnormalities as a risk factor for postoperative delirium revealed by diffusion tensor imaging. Am J Geriatr Psychiatry 18(8), 743–753. [2] Cavallari, M., Hshieh, T.T., Guttmann, C.R., Ngo, L.H., Meier, D.S., Schmitt, E.M., Marcantonio, E.R., Jones, R.N., Kosar, C.M., Fong, T.G., Press, D., Inouye, S.K., Alsop, D.C., 2015. Brain atrophy and white-matter hyperintensities are not significantly associated with incidence and severity of postoperative delirium in older persons without dementia. Neurobiol Aging 36(6), 2122–2129. [3] Cavallari, M., Dai, W., Guttmann, CR., Meier, DS., Ngo, LH., Hshieh, T.T., Callahan, A.E., Fong, T.G., Schmitt, E., Dickerson, B.C., Press, D.Z., Marcantonio, E.R., Jones, R.N., Inouye, S.K., Alsop, D.C., 2016. Neural substrates of vulnerability to postsurgical delirium as revealed by presurgical diffusion MRI. Brain, http://dx.doi.org/10.1093/ brain/aww010. [4] Trzepacz, P.T., 1999. Update on the neuropathogenesis of delirium. Dement Geriatr Cogn Disord 10(5), 330–334.
P.5.d.004 The effect of computer-assisted cognitive rehabilitation for patients with brain lesions S.B. Shin1 ° , T.U. Kim1 , J.Y. Moon1 , J.K. Hyun1 1 College of Medicine- Dankook University, Department of Rehabilitation Medicine, Cheonan, South-Korea Background: Stroke is the clinical syndrome of cerebral deficit with vascular events and the neuroimaging of brain lesion is required for diagnosis. In general, 25% of the patients show dementia 3 months after stroke, and 50−75% show partial memory and cognitive disorder [1]. Cognitive dysfunction reduces motivation and has a negative effect on functional recovery, so cognitive rehabilitation is necessary for stroke patients to improve their functional capabilities for performing independent daily activities [2]. Cognitive rehabilitation has a mechanism that can compensate for an impaired nervous system through the reinforcement, promotion and relearning [3]. At present, two major categories of cognitive training (traditional and computer-assisted) are widely used. Traditional cognitive rehabilitation varies depending on the therapist, and feedback is not consistent. However computerassisted cognitive rehabilitation provides instant and direct feedback for patient performance. In addition, it is possible that the rehabilitation program is specified to the damaged cognitive area, and the level of difficulty can be adjusted to the patient [4]. Objectives: The aim of this study is to elucidate the effect of computer-assisted cognitive rehabilitation compared with traditional cognitive rehabilitation in patients with stroke. Method: Retrospectively, We evaluated 70 subjects with stroke who underwent computer-assisted cognitive rehabilitation without premorbid cognitive impairment, disabling sensory alteration and severe psychiatric and medical illness. Cognitive impairment was evaluated using the Korean Mini-mental State Examination
(K-MMSE) and Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) before treatment. The follow-up evaluation of K-MMSE was conducted 1 month after starting treatment. We analyzed demographic variables such as age, sex and cause of stroke, length of hospitalization. Functional status was also measured using the Functional Independence Measure (FIM), Korean version modified Barthel index (K-MBI). We evaluated the same variables in cognitive function-matched controls for comparison between computer-assisted cognitive rehabilitation group and traditional cognitive rehabilitation group. All subjects were classified into three groups according to severity of cognitive impairment (mild: K-MMSE 21−25, moderate: K-MMSE 11−20, severe: K-MMSE 0−10) for subgroup analysis. Results: Two groups did not show significant difference in the FIM, K-MBI, K-MMSE, LOTCA before treatment, but the improvement of K-MMSE score after treatment was better in computer-assisted cognitive rehabilitation group (3.9±4.5 and 2.5±2.4, respectively; p = 0.03). In subgroup analysis, only subjects with severe cognitive impairment showed significant improvement of K-MMSE score (6.6±6.8 and 1.9±3.3, respectively; p < 0.05) and subjects with mild and moderate cognitive impairment did not have significant difference in K-MMSE before and after treatment. Demographic variables, length of hospitalization and cause of stroke were not different between two groups. Conclusion: We found that the effect of computer-assisted cognitive rehabilitation is better in subjects with severe cognitive impairment and similar in subjects with mild to moderate cognitive rehabilitation compared with traditional cognitive rehabilitation. The computer-assisted cognitive rehabilitation is considered as an alternative treatment modality of cognitive impairment in rehabilitation of stroke patients. References [1] Desmond, D.W., Moroney, J.T., Paik, M.C., Sano, M., Mohr, J.P., Aboumatar, S., Tseng, C.L., Chan, S., Wiliams, J.B., Remien, R.H., Hauser, W.A., Stern, Y., 2000. Frequency and clinical determinants of dementia after ischemic stroke. Neurology 54, 1124−31. [2] Zorowitz, R.D., Gross, E., Polinski, D.M., 2002. Effects of problemoriented willed-movement therapy on motor abilities for people with post stroke cognitive deficits. J Disabil Rehabil 24: 666–679. [3] Yang, S., Ye, H., Huang, J., Tao, J., Jiang, C., Lin, Z., Zheng, G., Chen, L., 2014. The synergistic effect of acupuncture and computerbased cognitive training on post-stroke cognitive dysfunction: a study protocol for a randomized controlled trial of 2×2 factorial design. BMC complement Altern Med 14, 290. [4] Park, I.S., Yoon, J.G., 2015. The effect of computer-assisted cognitive rehabilitation and repetitive transcranial magnetic stimulation on cognitive function for stroke patients. J Phys Ther Sci 27, 773−6.
P.5.d.005 CYP2D6 and catechol-O-methyltransferase gene polymorphisms in Parkinson patients with levodopa-induced dyskinesias S.A. Ivanova1 ° , V.M. Alifirova2 , I.V. Pozhidaev1 , O.Y. Fedorenko1 , D.Z. Osmanova1 , V.V. Tiguntsev1 , N.A. Bokhan3 , I.A. Zhukova2 , B. Wilffert4 , A.J.M. Loonen4 1 Mental Health Research Institute, Molecular Genetics and Biochemistry Laboratory, Tomsk, Russia; 2 Siberian State Medical University, Department of Neurology and Neurosurgery, Tomsk, Russia; 3 Mental Health Research Institute, Department of Clinical Psychiatry, Tomsk, Russia; 4 University of Groningen, Department of Pharmacy, Groningen, The Netherlands Parkinson’s disease (PD), a common neurodegenerative disorder caused by the loss of the dopaminergic input to the basal ganglia, is commonly treated with levodopa (L-DOPA). Use of this
P.5.d. Dementia and neurological disorders − Neurological disorders (clinical) drug, however, is severely limited by the development of side effect. Levodopa-induced dyskinesias (LID) are involuntary muscle movements that occur as a consequence of chronic levodopa (L-DOPA) treatment. LID are a substantial barrier to effective symptomatic management of Parkinson’s disease (PD), up to 45% of L-DOPA users develop LID within 5 years [1]. Clinical heterogeneity of LID suggests a significant role of endogenous factors in determining their prevalence. Some evidence suggest a relationship between LID and specific genetic changes, such as changes in the genes controlling enzymes responsible for drug and monoamine metabolism, neurotransmitter receptors and proteins involved in oxidative stress or antioxidant function [2−4]. Objective: To investigate contribution of polymorphic variants of CYP2D6 and COMT genes in the development of LID in PD patients. Methods: 212 patients with Parkinson’s disease on levodopa therapy were investigated. Dyskinesias were estimated with use of Abnormal Involuntary Movement Scale (AIMS). DNA extraction and fluorogenic 5 -exonuclease TaqMan genotyping assays were conducted according to standard protocols and blind to the clinical status of the subjects. Genotyping was carried out on 2 SNPs of CYP2D6 (CYP2D6*3, rs35742686; CYP2D6*4, rs3892097) and 7 SNPs of COMT genes (rs4680, rs6269, rs4633, rs4818, rs769224, rs165774, rs174696). The SPSS software was used for statistical analysis. Results: Patients in our cohort demonstrated typical PD demographics, with a mean age of onset of 60.04±9.46 years, a mean disease duration of 9.79±5.57 years. Dyskinesias were reported in 57 (26.9%) patients. The distribution of genotypes of studied genes corresponded to the Hardy–Weinberg equilibrium. Association of polymorphisms in CYP2D6 gene with side effects was not revealed. We found that rs4680 polymorphism in COMT gene is significantly associated with LID (c2 = 6.048, p = 0.049). Odds ratio for carriers of the genotype AA is 2.14 [95% CI: 1.11– 4.11], which indicates the predisposing effect of this genotype on the development of dyskinesias. Rs4680 is a functional SNP in genes encoding the catechol-O-methyltransferase enzyme, which catabolizes dopamine. A valine to methionine substitution at codon 158 of the COMT gene produces a Met variant that catabolizes dopamine up to four times slower than its Val counterpart. Conclusions: Polymorphisms in the COMT gene play significant role in the therapy response to L-DOPA as well as in various adverse effects. COMT is an extracellular enzyme which inactive variants increase the extracellular concentration of dopamine. This may increase the uptake of dopamine by indirect pathway MSN and therefore increase oxidative stress. We hypothesized that functional single nucleotide polymorphism rs4680 in COMT gene may result in a clinical phenotype contributing to an increased risk of LID. Thus, the polymorphism of gene possessing predisposing effects in development of levodopa induced dyskinesia in PD has been revealed that would allow predicting risk of development of movement disorders. References [1] Rascol, O., Brooks, D.J., Korczyn, A.D, et al. 2000. Study Group: A five–year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or L–DOPA. N Engl J Med 342, 1484–1491. [2] Lu, Y., Mo, C., Zeng, Z., et al. 2013. CYP2D6*4 allele polymorphism increases the risk of Parkinson’s disease: evidence from meta-analysis. PLoS One. 8(12): e84413. [3] Loonen, A.J.M., Ivanova, S.A. 2016. Role of 5-HT2C receptors in dyskinesia. International Journal of Pharmacy and Pharmaceutical Sciences. 8 (1), 5−10.
S657
[4] Cheshire, P., Bertram, K., Ling, H., et al. 2014. Influence of Single Nucleotide Polymorphisms in COMT, MAO-A and BDNF Genes on Dyskinesias and Levodopa Use in Parkinson’s Disease. Neurodegener Dis. 13(1): 24−28. Disclosure statement: This abstract is supported by the Russian Science Foundation (project no. 14−35–00023)
P.5.d.006 Concomitant administration of quetiapine/ rivastigmine in Parkinson’s disease dementia (PDD) G. Sulejmanpasic-Arslanagic1 ° , S. Bise2 1 University of Sarajevo Clinical Center, Psychiatric clinic, Sarajevo, Bosnia and Herzegovina; 2 Sarajevo Psychiatric Hospital, Clinical, Sarajevo, Bosnia and Herzegovina Introduction: Parkinson’s disease (PD) is a neurodegenerative disorder that affects an estimated tens of millions people worldwide older than 65 years, and the incidence is 2 percent. PD is the second most common neurodegenerative disease after Alzheimer’s disease, with clinical features (e.g., dementia, spontaneous parkinsonism, and attentional impairment). Dementia also occurs commonly in PD, affecting up to 75% of PD patients over the long term. Psychotic disorders (or psychoses) occurs rarely in untreated PD patients, those with comorbid late dementia, depression, or delirium are at the greatest risk [1,2]. Medication therapy has made significant advances and improvements especially over the last 10 years. A number of new treatments and new strategies have emerged and the quality of life for the average sufferer has improved. Atypical antipsychotic drugs are prescribed for elderly patients with symptoms of psychosis and behavioral disturbances. These symptoms often occur in patients with Parkinson’s disease. Hallucinations occur in up to 20 percent of patients with Parkinson’s disease, delusions, paranoia and subcortical dementia also may occur. Quetiapine has shown promise in the treatment of psychosis in elderly patients with Parkinson’s disease. It improves psychosis without exacerbating movement disorders [3]. Impairment of attention and memory in patients with Parkinson’s disease is associated with significantly lower levels of acetylcholine. Inhibition of the breakdown of acetylcholine by blocking the enzymes acetylcholinesterase and butyrylcholinesterase with rivastigmine improves this cholinergic depletion. Thus rivastigmine administration provides established, effective, long-term symptomatic treatment in patients with Parkinson’s disease dementia (PDD) [4]. Aim: The aim was to evaluate clinical efficacy, safety and tolerability of the concomitant use of quetiapine and rivastigmine in PDD patients. Methods: Six elderly male outpatients entered this 12-week single centre study to assess clinical efficacy of quetiapine and rivastigmine in PDD. Subjects were divided in two groups: quetiapine (N = 3) with dose of 300 mg/day and quetiapine/rivastigmine (N = 3) with dose of 150 mg/day and 6 mg/day. Psychiatric, motor and cognitive assessments were administered at baseline and at periodic intervals for 12 weeks. These included the Brief Psychiatric Rating Scale (BPRS), Neuropsychiatric Inventory (NP), Unified Parkinson’s Disease Rating Scale (UPDRS) and tests of intellectual functioning, attention and memory. Patients were in contact with neurologist as well all the time. Results: The results revealed significant improvements in the 12-weeks BPRDS total score and NPI psychosis subscale scores with significantly greater in quetiapine/rivastigmine group, with
P.5.d. Dementia and neurological disorders − Neurological disorders (clinical)
observed for 3 days without medication, non-dementia patients with postsurgical delirium with old lacunar infarct sequelae in the right thalamus had more severe delirium than non-dementia patients without old lacunar infarct sequelae in the right thalamus. Early, effective treatment of these patients should have a positive impact on postsurgical delirium. Our study supports the hypothesis that structural dysconnectivity involving the interhemispheric and fronto-thalamo-cerebellar networks predisposes to delirium under the stress of surgery [2]. The right thalamus may also play a significant role in aggravating postsurgical delirium. Further studies are needed to research the role of the left thalamus for postsurgical delirium in non-dementia patients. References [1] Shioiri, A., Kurumaji, A., Takeuchi, T., Matsuda, H., Arai, H., Nishikawa, T., 2010. White matter abnormalities as a risk factor for postoperative delirium revealed by diffusion tensor imaging. Am J Geriatr Psychiatry 18(8), 743–753. [2] Cavallari, M., Hshieh, T.T., Guttmann, C.R., Ngo, L.H., Meier, D.S., Schmitt, E.M., Marcantonio, E.R., Jones, R.N., Kosar, C.M., Fong, T.G., Press, D., Inouye, S.K., Alsop, D.C., 2015. Brain atrophy and white-matter hyperintensities are not significantly associated with incidence and severity of postoperative delirium in older persons without dementia. Neurobiol Aging 36(6), 2122–2129. [3] Cavallari, M., Dai, W., Guttmann, CR., Meier, DS., Ngo, LH., Hshieh, T.T., Callahan, A.E., Fong, T.G., Schmitt, E., Dickerson, B.C., Press, D.Z., Marcantonio, E.R., Jones, R.N., Inouye, S.K., Alsop, D.C., 2016. Neural substrates of vulnerability to postsurgical delirium as revealed by presurgical diffusion MRI. Brain, http://dx.doi.org/10.1093/ brain/aww010. [4] Trzepacz, P.T., 1999. Update on the neuropathogenesis of delirium. Dement Geriatr Cogn Disord 10(5), 330–334.
P.5.d.004 The effect of computer-assisted cognitive rehabilitation for patients with brain lesions S.B. Shin1 ° , T.U. Kim1 , J.Y. Moon1 , J.K. Hyun1 1 College of Medicine- Dankook University, Department of Rehabilitation Medicine, Cheonan, South-Korea Background: Stroke is the clinical syndrome of cerebral deficit with vascular events and the neuroimaging of brain lesion is required for diagnosis. In general, 25% of the patients show dementia 3 months after stroke, and 50−75% show partial memory and cognitive disorder [1]. Cognitive dysfunction reduces motivation and has a negative effect on functional recovery, so cognitive rehabilitation is necessary for stroke patients to improve their functional capabilities for performing independent daily activities [2]. Cognitive rehabilitation has a mechanism that can compensate for an impaired nervous system through the reinforcement, promotion and relearning [3]. At present, two major categories of cognitive training (traditional and computer-assisted) are widely used. Traditional cognitive rehabilitation varies depending on the therapist, and feedback is not consistent. However computerassisted cognitive rehabilitation provides instant and direct feedback for patient performance. In addition, it is possible that the rehabilitation program is specified to the damaged cognitive area, and the level of difficulty can be adjusted to the patient [4]. Objectives: The aim of this study is to elucidate the effect of computer-assisted cognitive rehabilitation compared with traditional cognitive rehabilitation in patients with stroke. Method: Retrospectively, We evaluated 70 subjects with stroke who underwent computer-assisted cognitive rehabilitation without premorbid cognitive impairment, disabling sensory alteration and severe psychiatric and medical illness. Cognitive impairment was evaluated using the Korean Mini-mental State Examination
(K-MMSE) and Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) before treatment. The follow-up evaluation of K-MMSE was conducted 1 month after starting treatment. We analyzed demographic variables such as age, sex and cause of stroke, length of hospitalization. Functional status was also measured using the Functional Independence Measure (FIM), Korean version modified Barthel index (K-MBI). We evaluated the same variables in cognitive function-matched controls for comparison between computer-assisted cognitive rehabilitation group and traditional cognitive rehabilitation group. All subjects were classified into three groups according to severity of cognitive impairment (mild: K-MMSE 21−25, moderate: K-MMSE 11−20, severe: K-MMSE 0−10) for subgroup analysis. Results: Two groups did not show significant difference in the FIM, K-MBI, K-MMSE, LOTCA before treatment, but the improvement of K-MMSE score after treatment was better in computer-assisted cognitive rehabilitation group (3.9±4.5 and 2.5±2.4, respectively; p = 0.03). In subgroup analysis, only subjects with severe cognitive impairment showed significant improvement of K-MMSE score (6.6±6.8 and 1.9±3.3, respectively; p < 0.05) and subjects with mild and moderate cognitive impairment did not have significant difference in K-MMSE before and after treatment. Demographic variables, length of hospitalization and cause of stroke were not different between two groups. Conclusion: We found that the effect of computer-assisted cognitive rehabilitation is better in subjects with severe cognitive impairment and similar in subjects with mild to moderate cognitive rehabilitation compared with traditional cognitive rehabilitation. The computer-assisted cognitive rehabilitation is considered as an alternative treatment modality of cognitive impairment in rehabilitation of stroke patients. References [1] Desmond, D.W., Moroney, J.T., Paik, M.C., Sano, M., Mohr, J.P., Aboumatar, S., Tseng, C.L., Chan, S., Wiliams, J.B., Remien, R.H., Hauser, W.A., Stern, Y., 2000. Frequency and clinical determinants of dementia after ischemic stroke. Neurology 54, 1124−31. [2] Zorowitz, R.D., Gross, E., Polinski, D.M., 2002. Effects of problemoriented willed-movement therapy on motor abilities for people with post stroke cognitive deficits. J Disabil Rehabil 24: 666–679. [3] Yang, S., Ye, H., Huang, J., Tao, J., Jiang, C., Lin, Z., Zheng, G., Chen, L., 2014. The synergistic effect of acupuncture and computerbased cognitive training on post-stroke cognitive dysfunction: a study protocol for a randomized controlled trial of 2×2 factorial design. BMC complement Altern Med 14, 290. [4] Park, I.S., Yoon, J.G., 2015. The effect of computer-assisted cognitive rehabilitation and repetitive transcranial magnetic stimulation on cognitive function for stroke patients. J Phys Ther Sci 27, 773−6.
P.5.d.005 CYP2D6 and catechol-O-methyltransferase gene polymorphisms in Parkinson patients with levodopa-induced dyskinesias S.A. Ivanova1 ° , V.M. Alifirova2 , I.V. Pozhidaev1 , O.Y. Fedorenko1 , D.Z. Osmanova1 , V.V. Tiguntsev1 , N.A. Bokhan3 , I.A. Zhukova2 , B. Wilffert4 , A.J.M. Loonen4 1 Mental Health Research Institute, Molecular Genetics and Biochemistry Laboratory, Tomsk, Russia; 2 Siberian State Medical University, Department of Neurology and Neurosurgery, Tomsk, Russia; 3 Mental Health Research Institute, Department of Clinical Psychiatry, Tomsk, Russia; 4 University of Groningen, Department of Pharmacy, Groningen, The Netherlands Parkinson’s disease (PD), a common neurodegenerative disorder caused by the loss of the dopaminergic input to the basal ganglia, is commonly treated with levodopa (L-DOPA). Use of this
P.5.d. Dementia and neurological disorders − Neurological disorders (clinical) drug, however, is severely limited by the development of side effect. Levodopa-induced dyskinesias (LID) are involuntary muscle movements that occur as a consequence of chronic levodopa (L-DOPA) treatment. LID are a substantial barrier to effective symptomatic management of Parkinson’s disease (PD), up to 45% of L-DOPA users develop LID within 5 years [1]. Clinical heterogeneity of LID suggests a significant role of endogenous factors in determining their prevalence. Some evidence suggest a relationship between LID and specific genetic changes, such as changes in the genes controlling enzymes responsible for drug and monoamine metabolism, neurotransmitter receptors and proteins involved in oxidative stress or antioxidant function [2−4]. Objective: To investigate contribution of polymorphic variants of CYP2D6 and COMT genes in the development of LID in PD patients. Methods: 212 patients with Parkinson’s disease on levodopa therapy were investigated. Dyskinesias were estimated with use of Abnormal Involuntary Movement Scale (AIMS). DNA extraction and fluorogenic 5 -exonuclease TaqMan genotyping assays were conducted according to standard protocols and blind to the clinical status of the subjects. Genotyping was carried out on 2 SNPs of CYP2D6 (CYP2D6*3, rs35742686; CYP2D6*4, rs3892097) and 7 SNPs of COMT genes (rs4680, rs6269, rs4633, rs4818, rs769224, rs165774, rs174696). The SPSS software was used for statistical analysis. Results: Patients in our cohort demonstrated typical PD demographics, with a mean age of onset of 60.04±9.46 years, a mean disease duration of 9.79±5.57 years. Dyskinesias were reported in 57 (26.9%) patients. The distribution of genotypes of studied genes corresponded to the Hardy–Weinberg equilibrium. Association of polymorphisms in CYP2D6 gene with side effects was not revealed. We found that rs4680 polymorphism in COMT gene is significantly associated with LID (c2 = 6.048, p = 0.049). Odds ratio for carriers of the genotype AA is 2.14 [95% CI: 1.11– 4.11], which indicates the predisposing effect of this genotype on the development of dyskinesias. Rs4680 is a functional SNP in genes encoding the catechol-O-methyltransferase enzyme, which catabolizes dopamine. A valine to methionine substitution at codon 158 of the COMT gene produces a Met variant that catabolizes dopamine up to four times slower than its Val counterpart. Conclusions: Polymorphisms in the COMT gene play significant role in the therapy response to L-DOPA as well as in various adverse effects. COMT is an extracellular enzyme which inactive variants increase the extracellular concentration of dopamine. This may increase the uptake of dopamine by indirect pathway MSN and therefore increase oxidative stress. We hypothesized that functional single nucleotide polymorphism rs4680 in COMT gene may result in a clinical phenotype contributing to an increased risk of LID. Thus, the polymorphism of gene possessing predisposing effects in development of levodopa induced dyskinesia in PD has been revealed that would allow predicting risk of development of movement disorders. References [1] Rascol, O., Brooks, D.J., Korczyn, A.D, et al. 2000. Study Group: A five–year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or L–DOPA. N Engl J Med 342, 1484–1491. [2] Lu, Y., Mo, C., Zeng, Z., et al. 2013. CYP2D6*4 allele polymorphism increases the risk of Parkinson’s disease: evidence from meta-analysis. PLoS One. 8(12): e84413. [3] Loonen, A.J.M., Ivanova, S.A. 2016. Role of 5-HT2C receptors in dyskinesia. International Journal of Pharmacy and Pharmaceutical Sciences. 8 (1), 5−10.
S657
[4] Cheshire, P., Bertram, K., Ling, H., et al. 2014. Influence of Single Nucleotide Polymorphisms in COMT, MAO-A and BDNF Genes on Dyskinesias and Levodopa Use in Parkinson’s Disease. Neurodegener Dis. 13(1): 24−28. Disclosure statement: This abstract is supported by the Russian Science Foundation (project no. 14−35–00023)
P.5.d.006 Concomitant administration of quetiapine/ rivastigmine in Parkinson’s disease dementia (PDD) G. Sulejmanpasic-Arslanagic1 ° , S. Bise2 1 University of Sarajevo Clinical Center, Psychiatric clinic, Sarajevo, Bosnia and Herzegovina; 2 Sarajevo Psychiatric Hospital, Clinical, Sarajevo, Bosnia and Herzegovina Introduction: Parkinson’s disease (PD) is a neurodegenerative disorder that affects an estimated tens of millions people worldwide older than 65 years, and the incidence is 2 percent. PD is the second most common neurodegenerative disease after Alzheimer’s disease, with clinical features (e.g., dementia, spontaneous parkinsonism, and attentional impairment). Dementia also occurs commonly in PD, affecting up to 75% of PD patients over the long term. Psychotic disorders (or psychoses) occurs rarely in untreated PD patients, those with comorbid late dementia, depression, or delirium are at the greatest risk [1,2]. Medication therapy has made significant advances and improvements especially over the last 10 years. A number of new treatments and new strategies have emerged and the quality of life for the average sufferer has improved. Atypical antipsychotic drugs are prescribed for elderly patients with symptoms of psychosis and behavioral disturbances. These symptoms often occur in patients with Parkinson’s disease. Hallucinations occur in up to 20 percent of patients with Parkinson’s disease, delusions, paranoia and subcortical dementia also may occur. Quetiapine has shown promise in the treatment of psychosis in elderly patients with Parkinson’s disease. It improves psychosis without exacerbating movement disorders [3]. Impairment of attention and memory in patients with Parkinson’s disease is associated with significantly lower levels of acetylcholine. Inhibition of the breakdown of acetylcholine by blocking the enzymes acetylcholinesterase and butyrylcholinesterase with rivastigmine improves this cholinergic depletion. Thus rivastigmine administration provides established, effective, long-term symptomatic treatment in patients with Parkinson’s disease dementia (PDD) [4]. Aim: The aim was to evaluate clinical efficacy, safety and tolerability of the concomitant use of quetiapine and rivastigmine in PDD patients. Methods: Six elderly male outpatients entered this 12-week single centre study to assess clinical efficacy of quetiapine and rivastigmine in PDD. Subjects were divided in two groups: quetiapine (N = 3) with dose of 300 mg/day and quetiapine/rivastigmine (N = 3) with dose of 150 mg/day and 6 mg/day. Psychiatric, motor and cognitive assessments were administered at baseline and at periodic intervals for 12 weeks. These included the Brief Psychiatric Rating Scale (BPRS), Neuropsychiatric Inventory (NP), Unified Parkinson’s Disease Rating Scale (UPDRS) and tests of intellectual functioning, attention and memory. Patients were in contact with neurologist as well all the time. Results: The results revealed significant improvements in the 12-weeks BPRDS total score and NPI psychosis subscale scores with significantly greater in quetiapine/rivastigmine group, with