Insular AD Pathology and Autonomic Function

岛状 AD 病理学和自主神经功能

• 批准号: 6967299
• 负责人: DONALD R ROYALL
• 金额: $ 16.88万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-22 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6967299
• 关键词: Alzheimer' s disease; aging; autonomic disorder; biomarker; bradycardia; cardiovascular disorder; frontal lobe /cortex; heart rate; human data; human tissue; longitudinal human study; pathologic process; postmortem

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.

描述（由申请人提供）：阿尔茨海默病（AD）痴呆代表了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之前，AD的病理可能已经到达了与心血管自主控制有关的岛叶皮层。右岛病变与慢速心律失常和死亡率增高有关。尸检研究表明，40%的八十多岁老人可能有患岛状阿尔茨海默病的风险。同样，在24小时动态心电图记录中，20-40%的健康八旬老人有不明原因的“年龄相关”室上性心律失常。视觉空间认知测量与阿尔茨海默病的死亡率有关。我们观察到类似测试与非痴呆老年退休人员死亡率之间存在强大的关联。因此，我们怀疑临床前AD可能是无痴呆老年人“年龄相关”自主神经功能障碍和“心血管”/跌倒相关发病率和死亡率的原因。