Synaptotagmin XI in Parkinson's disease: New evidence from an association study in Spain and Mexico.

INTRODUCTION: The pathophysiology of PD (Parkinson's disease) has been related to the ubiquitin proteasome system and oxidative stress. Parkin acts as ubiquitin ligase on several substrates. Because genetic variants often have different frequencies across populations, population specific analyses are necessary to complement and validate results from genome-wide association studies. METHODS: We carried out an association study with genes coding for parkin substrates and cellular stress components in the Galician population (Northern Spain). SNCA and MAPT SNPs were also analyzed. We studied 75 SNPs in a discovery sample of 268 PD patients and 265 controls from Galicia. A replication sample of 271 patients and 260 controls was recruited from Mexico City. RESULTS: We observed significant association between PD and SNPs in MAPT. Nominal p-values<0.05 were obtained in the Galician cohort for SNPs in SYT11, coding for synaptotagmin XI. These results were replicated in the Mexican sample. DISCUSSION: The associated markers lie within a ~140kb strong linkage disequilibrium segment that harbors several candidate genes, including SYT11. SNPs from the GBA-SYT11-RAB25 region have been previously associated with PD, however the functionally relevant variants remain unknown. Our data support a likely role of genetic factors within 1q22 in PD susceptibility.

Venous thromboembolism in immobilized patients with dementia. Findings from the RIETE registry.

BACKGROUND: The natural history of venous thromboembolism (VTE) in patients with dementia has not been thoroughly studied. METHODS: We used the RIETE Registry data to assess the clinical characteristics, treatment strategies and outcome during the first 3 months after acute VTE in all immobilized patients with dementia. RESULTS: As of August 2011, 37988 patients had been enrolled, of whom 1316 (3.5%) had dementia. Most patients in both subgroups were initially treated with low-molecular-weight heparin (LMWH). Then, 48% of patients with dementia and 25% of those without dementia received LMWH as long-term therapy. During the first 3 months of anticoagulant therapy, patients with dementia had a higher incidence of fatal pulmonary embolism (PE): 4.0% vs. 1.2% (odds ratio: 3.3; 95% CI: 2.5-4.4) and fatal bleeding: 1.4% vs. 0.5% (odds ratio: 2.9; 95% CI: 1.8-4.6) than those without dementia. In demented patients initially presenting with PE, the incidence of fatal PE during the first week outweighed that of fatal bleeding (42 vs. 4 deaths), but from Day 8, the incidence of fatal PE was similar to the incidence of fatal bleeding. In patients initially presenting with deep vein thrombosis (DVT), there were 4 fatal PE and 8 fatal bleeding events. CONCLUSIONS: VTE patients with dementia had a high incidence of fatal PE and fatal bleeding. In those initially presenting with PE, the risk of dying of PE far outweighed that of fatal bleeding. In patients presenting with DVT alone, the risk of fatal PE was lower than that of fatal bleeding.

Complicaciones del tratamiento en la enfermedad de Parkinson. Las discinesias / Complications in the treatment of Parkinson's disease. Dyskinesias

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Trastornos cognitivos y neuropsiquiátricos en la enfermedad de Parkinson / Cognitive and neuropsychiatric disorders in Parkinson’s disease

Introducción. En la enfermedad de Parkinson hay pacientes con déficit cognitivo aislado y múltiple y el rendimiento cognitivo forma un abanico que va desde la normalidad hasta un avanzado grado de demencia. La mayoría de los enfermos presenta un déficit ejecutivo, aislado o combinado con otras alteraciones cognitivas, que se considera lo mas característico de la enfermedad, y un 30-40% de afectados acabara presentando una demencia clínicamente definida. Desarrollo. La presencia de alteración cognitiva leve en los enfermos parkinsonianos significa la existencia de un riesgo elevado de aparición de demencia en el transcurso de la enfermedad. La demencia asociada con enfermedad de Parkinson esta específicamente relacionada con sintomatología neuropsiquiátrica, que puede tener tres posibles explicaciones: alteración de vías mesolímbicas, alteración cortical y límbica difusa, o fenomenología de tipo Alzheimer asociada. Los episodios psicóticos se presentan preferentemente en los pacientes con tratamiento dopaminérgico y el espectro clínico de la psicosis parkinsoniana abarca: ilusiones visuales, alucinaciones visuoaudioolfatorias, delirio y psicosis alucinatoria paranoide grave. Todos los fármacos antiparkinsonianos pueden provocar alucinaciones y psicosis, pero los agonistas dopaminérgicos detentan la mayor capacidad. Conclusiones. En el manejo de esta problemática es muy importante la prevención y el diagnóstico y tratamiento tan pronto hagan aparición. Han de disminuirse las dosis de antiparkinsonianos, aunque ello no suele ser suficiente, por lo que habrá que asociar antipsicóticos atípicos, que actúen preferentemente sobre receptores 5-HT y no produzcan bloqueo D2, la mayoría de las veces (AU)

Introduction. In Parkinson’s disease there are patients with isolated and multiple cognitive impairment, and their cognitive performance ranges from normal to an advanced degree of dementia. Most patients present an executive deficit, either in isolation or combined with other cognitive disorders, which is considered to be the most characteristic aspect of the disease, and 30-40% of those affected will end up with a clinically-defined dementia. Development. The presence of a mild cognitive disorder in patients with Parkinson means that the risk of dementia appearing at some time during the development of the disease is high. The dementia associated with Parkinson’s disease is specifically related with neuropsychiatric signs and symptoms, which may have three possible explanations: disorders affecting the mesolimbic pathways, diffuse limbic and cortical compromise, or associated Alzheimer-type phenomenology. Psychotic episodes tend to present more often in patients with dopaminergic treatment and the clinical spectrum of Parkinson-related psychosis covers visual illusions, visual-audio-olfactory hallucinations, delirium and severe paranoid hallucinatory psychosis. All the antiparkinsonian drugs can give rise to hallucinations and psychosis, but the dopamine agonists are the ones with the greatest capacity to do so. Conclusions. In managing these problems, it is crucial for prevention as well as diagnosis and treatment to be carried out as soon as they are detected. Doses of antiparkinsonian drugs must be reduced, although this is not usually enough, and so it will be necessary to associate atypical antipsychotics, which act mainly on 5-HT receptors and, in most cases, do not produce D2 blockage (AU)