Dyspraxia and Autonomic Control in Very Early AD

描述（由申请人提供）： 阿尔茨海默氏痴呆症只是一个跨越数十年的病理过程的最后阶段。在临床医生能够检测到痴呆症之前，AD病理可能已经到达岛叶皮层，这与心率和血压的自主控制有关。岛叶病变，尤其是右侧岛叶病变，与缓慢性心律失常、心率变异性（HRV）降低和死亡率增加相关。因此，临床前AD应被视为非痴呆老年人“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%的老年人可能有这种程度的AD病理学风险。在24小时动态霍尔特记录中，20-40%的健康老年人有无法解释的“年龄相关”室上性心律失常。AD的死亡率与右半球代谢和结构性实践测试特别相关。这种影响不仅限于临床AD。在患有“轻度认知障碍”（MCI）的病例中，生存率也会降低。我们最近观察到，非痴呆、非残疾、独立生活的老年人中有轻度结构性损伤的死亡率增加。死亡率也与出现前AD的体征（如嗅觉丧失）相关。这表明AD在疾病过程的临床前阶段对死亡率具有显著影响。本研究将在三个水平的认知损害[例如，坦率的AD、轻度认知损害（MCI）（即，临床前AD）和正常对照]下检查右半球功能障碍与自主控制之间的关联。所有受试者均无严重心脏病（CAD）。将通过测量结构性实践和功能性磁共振成像（fMRI）的局部脑血流量来评估右半球功能。将通过对24份霍尔特记录的HRV进行统计分析，并辅以选定心律失常的频率和严重程度、直立性血压和症状自我报告，评估自主神经控制。在有AD风险的非痴呆患者中，右半球功能对自主控制的显著影响将具有重要意义。MCI的社区患病率估计为社区居住老年人的38%。建设性任务可以帮助识别那些有风险的人。少数群体的脆弱性可能不成比例。已知一些痴呆症治疗可以降低HRV，并可能降低死亡率。另外，一些精神药物可能通过中枢机制增加与疟疾相关的死亡率。

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.