Dyspraxia and Autonomic Control in Very Early AD

描述(由申请人提供)： 阿尔茨海默氏症只是一个跨越数十年的病理过程的最后阶段。在临床医生发现痴呆症之前，AD的病理可能已经到达岛叶皮质，这与自主控制心率和血压有关。岛状病变，特别是右侧，与缓慢性心律失常、心率变异性(HRV)降低和死亡率增加有关。因此，临床前AD应被认为是非痴呆老年人“心血管”I跌倒相关发病率和死亡率的可能解释。尸检研究表明，40%的八旬老人可能面临这种程度的AD病理风险。在24小时的Holter记录中，20-40%的健康的八旬老人有不明原因的与年龄有关的室上性心律失常。阿尔茨海默病的死亡率与右脑新陈代谢和构造性练习测试有明确的相关性。这种影响并不局限于临床AD。患有“轻度认知障碍”(MCI)的患者存活率也会降低。我们最近观察到，有轻度结构障碍的非痴呆、非残疾、独立的活着的八旬老人的死亡率增加。死亡率也与早期AD症状(如嗅觉障碍)有关。这表明AD在疾病过程的临床前阶段对死亡率有显著影响。本研究将从认知功能障碍的三个层面[如坦率的AD、轻度认知损害(MCI)(即临床前AD)和正常对照组]来考察右脑功能障碍与自主神经控制之间的关系。所有受试者都将没有严重的心脏病(CAD)。右脑功能将通过功能磁共振成像(FMRI)测量的结构活动和局部脑血流量进行评估。自主控制将通过对来自24个Holter记录的HRV的统计分析进行评估，并辅之以选定的心律失常、立位血压和症状自我报告的频率和严重程度。右脑功能对非痴呆AD高危人群自主神经控制的显著影响将具有重要意义。社区MCI的患病率估计在社区居住的老年人中占38%。施工任务可以帮助识别那些处于危险中的人。少数族裔可能特别容易受到伤害。众所周知，一些痴呆症治疗方法可以降低HRV，可能还会降低死亡率。或者，一些精神药物可能会增加心律失常相关的死亡率，可能是通过中枢机制。

DESCRIPTION (provided by applicant): Alzheimer's dementia is merely the final stage of a pathological process that spans decades. Before clinicians can detect dementia, AD pathology may have already reached the insular cortex, which is related to autonomic control of heart rate and blood pressure. Insular lesions, particularly on the right, are associated with bradyarrhythmias, decreased heart rate variability (HRV), and increased mortality. Thus, preclinical AD should be considered as a possible explanation for "cardiovascular" I fall-related morbidity and mortality in non-demented elderly persons. Autopsy studies suggest that 40% of octogenarians may be at risk for this level of AD pathology. 20-40% of healthy octogenarians have unexplained "age related" supaventricular arrhythmias on 24-hour Holter records. Mortality in AD is specifically associated with right hemisphere metabolism and tests of constructional praxis. This effect is not limited to clinical AD. Survival is decreased in cases with "Mild Cognitive Impairment" (MCI) as well. We have recently observed increased mortality in non-demented, non-disabled, independent living octogenarians with mild constructional impairments. Mortality was also associated with signs of pre-emergent AD (like anosmia). This suggests that AD has significant effects on mortality at a preclinical stage in the disease process. This study will examine the association between right hemisphere dysfunction and autonomic control at three levels of cognitive impairment [e.g. frank AD, Mild Cognitive Impairment (MCI) (i.e. preclinical AD), and normal controls]. All subjects will be free of significant cardiac disease (CAD). Right hemisphere function will be assessed by measures of constructional praxis, and regional cerebral blood flow by Functional Magnetic Resonance Imaging (fMRI). Autonomic control will be assessed by statistical analyses of HRV derived from 24 Holter records, supplemented by the frequency and severity of selected cardiac arrhythmias, orthostatic blood pressures, and symptom self-reports. A significant effect of right hemisphere function on autonomic control in non-demented persons at risk for AD would have important implications. The community prevalence of MCI has been estimated to be 38% of community dwelling elderly. Constructional tasks could help identify those at risk. Minorities may be disproportionately vulnerable. Some dementia treatments are known to reduce HRV, and possibly mortality as well. Alternatively, some psychotropics may increase arrhythmia-related mortality, possibly via a central mechanism.