María Teresa Periñán1,2, Daniel Macías-García1,2, Silvia Jesús1,2, Juan Francisco Martín-Rodríguez1,2,3, Laura Muñoz-Delgado1,2, Maria Valle Jimenez-Jaraba1, Dolores Buiza-Rueda1,2, Marta Bonilla-Toribio1,2, Astrid Daniela Adarmes-Gómez1,2, Pilar Gómez-Garre4,5, Pablo Mir6,7,8. 1. Servicio de Neurología y Neurofisiología Clínica, Unidad de Trastornos del Movimiento, Instituto de Biomedicina de Sevilla, (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013, Seville, Spain. 2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. 3. Departamento de Psicología Experimental, Facultad de Psicología, Universidad de Sevilla, Seville, Spain. 4. Servicio de Neurología y Neurofisiología Clínica, Unidad de Trastornos del Movimiento, Instituto de Biomedicina de Sevilla, (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013, Seville, Spain. mgomez-ibis@us.es. 5. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. mgomez-ibis@us.es. 6. Servicio de Neurología y Neurofisiología Clínica, Unidad de Trastornos del Movimiento, Instituto de Biomedicina de Sevilla, (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013, Seville, Spain. pmir@us.es. 7. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. pmir@us.es. 8. Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla, Seville, Spain. pmir@us.es.
Abstract
BACKGROUND: Hyperhomocysteinemia is considered an independent risk factor for cognitive impairment. OBJECTIVE: To study the correlation between homocysteine levels and cognitive impairment in patients with PD. METHODS: We conducted a case-control study that included 246 patients with PD, of whom 32 were cognitively impaired. The levels of homocysteine, folate, and vitamin B12 were measured in peripheral blood. Multivariate logistic regression analysis was applied to determine differences in homocysteine levels between PD patients with and without cognitive impairment. A meta-analysis was performed to clarify the role of Hcy levels in PD with cognitive decline. Five polymorphisms in genes involved in Hcy metabolism, including MTHFR rs1801133 and rs1801131, COMT rs4680, MTRR rs1801394, and TCN2 rs1801198, were genotyped. RESULTS: Our case-control study showed that homocysteine levels were associated with cognitive impairment in PD after adjusting for possible confounding factors such as levodopa equivalent daily dose. The results of our meta-analysis further supported the positive association between homocysteine levels and cognition in PD. We found that the MTHFR rs1801133 TT genotype led to higher homocysteine levels in PD patients, whereas the MTHFR rs1801131 CC genotype resulted in higher folate levels. However, the polymorphisms studied were not associated with cognitive impairment in PD. CONCLUSIONS: Increased homocysteine levels were a risk factor for cognitive decline in PD. However, no association was found between polymorphisms in genes involved in homocysteine metabolism and cognitive impairment in PD. Large-scale studies of ethnically diverse populations are required to definitively assess the relationship between MTHFR and cognitive impairment in PD.
BACKGROUND: Hyperhomocysteinemia is considered an independent risk factor for cognitive impairment. OBJECTIVE: To study the correlation between homocysteine levels and cognitive impairment in patients with PD. METHODS: We conducted a case-control study that included 246 patients with PD, of whom 32 were cognitively impaired. The levels of homocysteine, folate, and vitamin B12 were measured in peripheral blood. Multivariate logistic regression analysis was applied to determine differences in homocysteine levels between PD patients with and without cognitive impairment. A meta-analysis was performed to clarify the role of Hcy levels in PD with cognitive decline. Five polymorphisms in genes involved in Hcy metabolism, including MTHFR rs1801133 and rs1801131, COMT rs4680, MTRR rs1801394, and TCN2 rs1801198, were genotyped. RESULTS: Our case-control study showed that homocysteine levels were associated with cognitive impairment in PD after adjusting for possible confounding factors such as levodopa equivalent daily dose. The results of our meta-analysis further supported the positive association between homocysteine levels and cognition in PD. We found that the MTHFR rs1801133 TT genotype led to higher homocysteine levels in PD patients, whereas the MTHFR rs1801131 CC genotype resulted in higher folate levels. However, the polymorphisms studied were not associated with cognitive impairment in PD. CONCLUSIONS: Increased homocysteine levels were a risk factor for cognitive decline in PD. However, no association was found between polymorphisms in genes involved in homocysteine metabolism and cognitive impairment in PD. Large-scale studies of ethnically diverse populations are required to definitively assess the relationship between MTHFR and cognitive impairment in PD.
Authors: José Javier Martín-Fernández; Rafael Carles-Díes; Francisco Cañizares; Soledad Parra; Francisco Avilés; Irene Villegas; Ossama Morsi-Hassan; Andrés Fernández-Barreiro; M Trinidad Herrero Journal: Rev Neurol Date: 2010 Feb 1-15 Impact factor: 0.870