Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease.

There is increasing evidence for the involvement of blood-brain barrier (BBB) in vascular dementia (VaD) and Alzheimer´s disease (AD) pathogenesis. However, the role of endothelial function-related genes in these disorders remains unclear. We evaluated the association of four single-nucleotide polymorphisms (VEGF, VEGFR2 and NOS3) with diagnosis and rate of cognitive decline in AD and VaD in a Spanish case-control cohort (150 VaD, 147 AD and 150 controls). Participants carrying -604AA genotype in VEGFR2 (rs2071559) were less susceptible to VaD after multiple testing. Further analysis for VaD subtype revealed a significant difference between small-vessel VaD patients and controls, but not for large-vessel VaD patients. In addition, -2578A and -460C alleles in VEGF (rs699947 and rs833061) showed to decrease the risk of AD, whereas NOS3 (rs1799983) influenced disease progression. Our study supports previous findings of a deleterious effect of VEGFR2 reduced expression on small-vessel disease, but not on large-vessel disease; as well as a detrimental effect of down-regulating VEGF and eNOS in AD, affecting vascular permeability and neuronal survival. These data highlight the relevance of endothelial function and, therefore, BBB in both VaD and AD.

Síntomas no motores en la enfermedad de Parkinson y estimulación cerebral profunda / Nonmotor symptoms in Parkinson’s disease and deep brain stimulation

Introducción. La cirugía funcional ha adquirido gran relevancia en el tratamiento de las complicaciones motoras de la enfermedad de Parkinson (EP) avanzada, y menos conocida es la influencia de la estimulación cerebral profunda (ECP) en los síntomas no motores (SNM). Objetivo. Revisar la bibliografía sobre ECP y SNM en la EP. Desarrollo. Los resultados de la cirugía funcional sobre los SNM de la EP son variables en los distintos estudios. Algunos síntomas mejoran –trastornos del sueño, dolor o disconfort, trastornos obsesivo-compulsivos– y empeoran o aparecen otros –fluencia verbal, apatía, aumento de peso–. En estudios aislados se encuentra mejoría en memoria de trabajo, secuenciación visuomotora y razonamiento, algunos trastornos digestivos, genitourinarios, de termorregulación y olfativos, y empeoran la memoria verbal (recuerdo diferido) y visuoespacial, la velocidad psicomotora y la función ejecutiva, mientras que otros síntomas –hipotensión ortostática– no muestran cambios. Existen otros factores, además de la estimulación, que pueden modificar los SNM, como la vulnerabilidad preoperatoria individual, la disminución de medicación dopaminérgica tras la cirugía, la propia EP y los cambios psicosociales. En pacientes con perfiles determinados pueden existir riesgos específicos –mayor riesgo de alteración cognitiva en pacientes de más de 69 años o con alteración cognitiva precirugía; mayor riesgo de depresión, manía o suicidio en pacientes con patología psiquiátrica previa–. Conclusiones. Es necesario valorar el riesgo-beneficio individualmente para obtener resultados óptimos con este tratamiento. Se requieren estudios multicéntricos que permitan esclarecer el papel de la ECP sobre los SNM (AU)

Introduction. The efficacy of deep brain stimulation (DBS) for the motor symptoms of advanced Parkinson’s disease (PD) is well established. However, the effects of DBS on nonmotor symptoms (NMS) are less clear. Aim. To review the published literature on nonmotor aspects of DBS for PD. Development. The outcome of NMS after DBS in PD varies across studies. Some symptoms improve –sleep disorders, pain or sensory complaints, obsessive-compulsive disorder– and other aspects decline or appear –word fluency, apathy, body weight gain–. Isolated studies note mild improvements in working memory, visuomotor sequencing and conceptual reasoning, some gastrointestinal, urogenital, sweating and olfactory disturbances; whereas other studies have reported declines in verbal memory (long delay recall), visuospatial memory, processing speed and executive function; orthostatic hypotension remains without changes. The reasons for such a range of symptoms observed is due to the multifactorialetiology of the NMS, including preoperative vulnerability, changes in dopaminergic medications, surgical and stimulation effects, underlying PD-related factors and psychosocial effects. Specific patient subgroups may be at greater risk of cognitive deficits –e.g., those older than 69 years or with cognitive impairment prior to surgery– or depression, mania and suicide –e.g., those ones with preoperative psychiatric symptoms–.Conclusions. Patients who undergo DBS must be well-selected, weighing the risks and benefits, in order to obtain the best results with this treatment. Further multicentre studies are necessary to understand the role of DBS on NMS (AU)