NEUROBEHAVIOR, NEUROCHEMISTRY, AND NEUROPATHOLOGY OF OPC

描述(调查人员摘要)：我们的长期目标是 了解以老年性痴呆为主的患者脑内的特殊改变 遗传性橄榄桥小脑萎缩[OPCA] 神经行为障碍和这种情况的病因。这 将通过密集的多学科方法来实现 涉及每年30次的神经学和神经心理学评估 美国OPCA患者和在尸检随访中的尸检脑 神经化学和神经病理学分析。我们的具体目标是： 1)明确脑胆碱能系统功能障碍在 OPCA的认知缺陷； 2)通过以下途径确定可能导致OPCA的生化因素 死后脑内磷脂和能量代谢的检测 过程和程序化的细胞死亡机制； 3)建立OPCA作为早期黑质纹状体多巴胺神经元模型 退化和退化 4)通过睡眠障碍干预改善OPCA患者的生活质量。 我们预计，这些研究将确定参与 OPCA的脑退行性变及其相关脑结构 对于这种障碍的认知障碍，在一些患者中， 是一个重要的临床管理问题。所得到的结果也是 可能与其他脑部疾病的病理生理过程有关 脊柱小脑性共济失调和更常见的人脑 病情[阿尔茨海默病、帕金森氏病、正常衰老] 它们与OPCA具有相同的某些生化特征。

DESCRIPTION (Investigator's Abstract): Our long-term goal is to understand the specific changes in brain of patients with dominantly a inherited olivopontocerebellar atrophy [OPCA) responsible for the neurobehavioural disturbances and the etiology of this condition. This will be achieved through an intensive multidisciplinary approach involving annual neurological and neuropsychological assessment of 30 U.s. OPCA patients and, at autopsy follow-up, postmortem brain neurochemical and neuropathological analyses. Our specific aims are to: 1) define the role of brain cholinergic system dysfunction in the cognitive deficits of OPCA; 2) determine the biochemical factors which might cause OPCA through examination in postmortem brain of phospholipid and energy metabolic processes, and programmed cell death mechanisms; 3) establish OPCA as a model of early nigrostriatal dopamine neurone degeneration and 4) improve the life of the OPCA patient through dvsohaaia intervention. We expect that these studies will identify processes involved in the brain degeneration of OPCA as well as the brain structures responsible for the cognitive impairment of this disorder which, in some patients, is an important clinical management issue. The obtained results are also likely to be relevant to brain pathophysiological processes in other spino cerebellar ataxia disorders and in more common human brain conditions [Alzheimer's disease, Parkinson's disease, normal aging) which share with OPCA certain biochemical features.