Insular AD Pathology and Autonomic Function

描述（由申请人提供）：阿尔茨海默病（AD）的痴呆代表了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之前，AD病理可能已经到达与心血管自主控制相关的岛叶皮层。右岛叶病变与缓慢性心律失常和死亡率增加有关。尸检研究表明，40%的老年人可能有患岛叶AD病理学的风险。同样，20-40%的健康老年人在24小时动态霍尔特记录中有无法解释的“年龄相关”室上性心律失常。视觉空间认知测量与AD死亡率相关。我们已经观察到类似的测试和非痴呆老年退休人员的死亡率之间存在强有力的关联。因此，我们怀疑，临床前AD可能是负责“年龄相关的”自主神经功能障碍和“心血管”/跌倒相关的发病率和死亡率在非痴呆老年人。 本研究将探讨特定的独立协会之间的岛屿AD和非AD 尸检病理和死前心血管自主神经功能的纵向变化， 檀香山-亚洲老龄化研究（哈斯）的参与者。哈斯是心脏病的纵向研究 8006名日裔美国人中的中风和中风。哈斯从1965年开始进行心血管检查， 1967年，1971年，1991年，1994年，1997年，1999年，1901年加上1991年以来的一系列认知测试和持续的监视. 600 进行了尸体解剖（约占最近死亡人数的20%）。大多数人都有完整的 临床数据存档。N = 1523例受试者留在活性哈斯队列中，提供了潜在的 未来的前瞻性研究的协会，我们证明在这个建议。 岛叶AD病理对痴呆或非痴呆患者自主控制的显著影响 有患AD风险的人将产生重要影响。自主神经功能障碍可以提供 未来AD痴呆转换风险的敏感指标，而针对室上性痴呆的干预措施， 缓慢性心律失常可降低AD早期阶段的死亡率。

DESCRIPTION (provided by applicant): The dementia of Alzheimer's disease (AD) represents the final stages of a pathological process that spans decades. Before clinicians can detect dementia, AD pathology may already have reached the insular cortex, which is related to cardiovascular autonomic control. Right insular lesions are associated with bradyarrhythmias and increased mortality. Autopsy studies suggest that 40% of octogenarians may be at risk for insular AD pathology. Similarly, 20-40% of healthy octogenarians have unexplained "age related" supaventricular arrhythmias on 24-hour Holter records. Visuospatial cognitive measures are associated with mortality in AD. We have observed a robust association between similar tests and mortality in non-demented elderly retirees. Thus, we suspect that preclinical AD may be responsible for "age-related" autonomic dysfunction and "cardiovascular" /fall related morbidity and mortality in nondemented elderly persons. This study will examine the specific independent associations between insular AD and non-AD pathology at autopsy and antemortem longitudinal change in cardiovascular autonomic function among participants in the Honolulu-Asia Aging Study (HAAS). HAAS is a longitudinal study of heart disease and stroke among 8006 Japanese-American men. HAAS involves cardiovascular exams from 1965, '67, '71, '91, '94, '97, '99, '01 plus serial cognitive exams since '91 and ongoing surveillance. 600 autopsies have been performed (approximately 20% of recent decedents). The majority have full clinical data on file. N = 1523 subjects remain in the active HAAS cohort, providing the potential for future prospective studies of the associations we demonstrate in this proposal. A significant effect of insular AD pathology on autonomic control in either demented or non-demented persons at risk for AD would have important implications. Autonomic dysfunction could provide a sensitive indicator of future AD dementia conversion risk, while interventions against supraventricular bradyarrhythmias may decrease mortality in the earlier stages of AD.