Insular Autonomic Function in Depression

描述（由申请人提供）：老年人的抑郁症状与晕厥、跌倒和死亡率有关。这些关联与合并症无关，可能反映了中枢神经系统的影响。我们一直在研究作为阿尔茨海默病（AD）类似问题的原因的岛屿病理。阿尔茨海默病的病理在临床前阶段到达岛岛，这可能影响40%的70岁老人。岛状AD病变，尤其是右侧，与慢性心律失常、Qtc间隔和死亡率相关。此外，右半球代谢和视觉空间技能可以预测中风、癫痫和阿尔茨海默病的死亡率。然而，我们现在可以证明，视觉空间认知障碍也介导了抑郁症状对死亡率的影响。这意味着抑郁症的死亡风险与右半球功能障碍有关。因此，老年人抑郁症相关死亡率的不成比例的风险可能是由他们亚临床结构性岛岛病变的风险增加介导的，包括中风、路易体和/或亚临床AD病理。本研究将确定3T磁共振成像（MRI）对右岛血流的不对称减少是否介导抑郁症状和自主神经功能测量之间的关联，而自主神经功能先前已与老年人群的死亡率相关。我们的主要结果将是Holter衍生的R-R频率变化的频谱分布中低频：高频分量的比例。额外的心率变异性（HRV）测量和心率HRV的纵向变化将用于二次分析。探索性分析将解决其他MRI病理标记作为潜在的介质。重要的调解将对公共卫生产生重要影响。38%的社区居住老年人有“轻度认知障碍”，根据亚临床岛型阿尔茨海默病病理可能存在风险。48%的大脑中动脉中风会影响脑岛。少数人患AD病理和抑郁症状的风险不成比例。此外，药物可能与岛屿病理相互作用，影响死亡风险。例如，精神类药物会影响岛血流量。这也许可以解释最近关于接受非典型抗精神病药或胆碱酯酶抑制剂的老年患者死亡率增加的报道。甚至抗抑郁药也可能加重这种风险，因为它们不能可靠地改善与抑郁相关的HRV变化，而且它们本身是晕厥、跌倒和髋部骨折的独立预测因子。简单的筛选测试，如画钟，可以识别出那些风险最大的人。公众相关性：老年人的抑郁症状与晕厥、跌倒、骨折和死亡有关。这项研究将确定右岛功能障碍是否可能是这些问题的原因。简单的绘图测试可以识别出那些处于危险中的人。其中可能包括多达38%的社区居住老年人患有“轻度认知障碍”（MCI），或24%的大脑中动脉中风患者。少数民族面临的风险可能更大。此外，岛岛功能障碍可以解释最近关于接受几种精神药物治疗的老年患者死亡率增加的报道。

DESCRIPTION (provided by applicant): Depressive symptoms in the elderly are associated with syncope, falls, and mortality. These associations are independent of comorbid conditions, and may reflect central nervous system effects. We have been investigating insular pathology as a cause of similar problems in Alzheimer's disease (AD). AD pathology reaches the insula at a preclinical stage, which may affect 40% of septuagenarians. Insular AD lesions, particularly on the right, are associated with bradyarrhythmias, Qtc intervals, and mortality. Moreover, right hemisphere metabolism and visuospatial skills predict mortality in stroke, and epilepsy as well as AD. However, we can now show that visuospatial cognitive impairments also mediate the effect of depressive symptoms on mortality. This implicates right hemisphere dysfunction in depression's mortality risk. Thus, the diproportionate risk of depression related mortality in the elderly may be mediated by their increased risk of subclinical structural insular lesions, including stroke, Lewy Body and /or subclinical AD pathology. This study will determine whether assymetric reductions in right insular blood flow by 3T magnetic resonance imaging (MRI) mediates the associaiton between depressive symptoms and measures of autonomic function, which have previously been associated with mortality in elderly populations. Our Primary Outcome will be the ratio of low frequency: high frequency components in the spectral distribution of Holter derived R-R frequency variations. Additonal heart rate variability (HRV) measures and longitudinal changes in heart rate HRV will be used in Secondary Analyses. Exploratory analyses will address other MRI pathological markers as potential mediators. Significant mediation would have important public health implications. 38% of community dwelling elderly with "Mild Cognitive Impairment" and could be at risk on the basis of subclinical insular AD pathology. 48% of middle cerebral artery strokes affect the insula. Minorities are disporportionately at risk for combined AD pathology and depressive symptoms. Moreover, medications may interact with insular pathology to affect mortality risk. Psychotropics, for example, affect insular blood flow. This may explain recent reports of increased mortality in eldely patients receiving atypical neuroleptics or cholinesterase inhibitors. Even anti-depressants may aggravate this risk, as they do not reliably improve depression related changes in HRV, and are themselves independent predictors of syncope, falls and hip fracture. Simple screening tests, such as clock- drawing, may identify those at greatest risk. PUBLIC RELEVANCE: Depressive symptoms in the elderly are associated with fainting spells, falls, bone fractures, and death. This study will determine whether right insular dysfunction may be a cause of these problems. Simple drawing tests may identify those at risk. These may include as many as 38% of community dwelling elderly with "Mild Cognitive Impairment" (MCI), or 24% of persons with middle cerebral artery strokes. Minorities may be disporportionately at risk. Moreover, insular dysfunction could explain recent reports of increased mortality in eldely patients receiving several types of psychotropic medications.