RISK AND PROTECTION FACTORS FOR NORMAL AND ABNORMAL BRAIN AGEING: A LONGITUDINAL EPIDEMIOLOGICAL MRI STUDY

大脑被认为是医学的最后前沿，老龄化是21世纪医疗保健的主要挑战。在这项提案中，我们将这两个挑战结合在一起，在最近启动的一项关于堪培拉老龄化的重大纵向研究中。这是一项纵向研究，随机抽取3个年龄组--20-24岁、40-44岁和60-年龄组，每个年龄组至少2000名参与者在1999-2001年接受评估，并将每隔4年进行一次跟踪调查，为期20年。这项研究的重点是神经精神障碍(焦虑、抑郁、物质使用和认知障碍)。在这项应用中，我们建议对60名样本中的四分之一(n-500名)进行磁共振扫描和血液测试，以获得脑形态的流行病学样本。我们不仅能够研究大脑形态随时间的变化，并将其与认知功能和精神障碍联系起来，我们还将能够评估风险和保护因素的作用。我们特别感兴趣的是大脑储备、饮食因素(抗氧化剂、omega 3、葡萄酒和叶酸)和药物(抗炎药、激素替代药物和维生素补充剂)作为保护因素，以及高血压、同型半胱氨酸水平、MRI脑白质损害和低海马体体积作为认知障碍和痴呆的风险因素。我们还想在社区样本中研究抑郁症的大脑形态相关性。这项研究将加强我们对大脑老化的了解，无论是在健康方面还是在疾病方面，并确定在老年时增加或降低认知障碍和精神障碍风险的因素。

Brain is considered the last frontier of medicine, and ageing the major challenge to health care in the 21st century. In this proposal, we bring these two challenges together in a major new longitudinal study of ageing in Canberra that has recently been initiated. This is a longitudinal study of a random community sample covering 3 age groups - 20-24 years, 40-44 years and 60-64 years, with at least 2000 participants in each age group - who are being assessed in 1999-2001, and will be followed up at 4-yearly intervals for 20 years. The focus of the study is on neuropsychiatric disorders (anxiety, depression, substance use and cognitive disorders). In this application, we propose to perform MRI scans and blood tests on a quarter (n-500) of the 60-64 sample to obtain an epidemiological sample for brain morphology. Not only will we be able to study changes in brain morphology over time, and relate it with cognitive function and psychiatric disorder, we will also be able to assess the role of risk and protection factors. We are particularly interested in brain reserve, dietary factors (anti-oxidants, omega 3, wine and folate) and drugs (anti-inflammatory drugs, hormone replacement and vitamin supplements) as protection factors, and hypertension, homocysteine levels, white matter lesions on MRI and low hippocampal volumes as risk factors for cognitive impairment and dementia. We also want to study the brain morphological correlates of Depression in a community sample. The study will enhance our understanding of the ageing brain, both in health and disease, and identify factors that increase or decrease the risk of cognitive impairment and psychiatric disorder in old age.