PREDICTING MRI ABNORMALITIES WITH LONGITUDINAL DATA OF THE WHITEHALL II SUBSTUDY

随着年龄的增长，许多人出现记忆问题和抑郁。它们与心脏病发作和中风的风险因素相同。因此，我们认为，记忆问题和晚年抑郁与脑血管疾病的典型大脑变化有关。通常情况下，神经纤维连接所在的脑白质在结构上受到干扰，而由于脑细胞的减少，灰质萎缩。幸运的是，大脑有许多策略来补偿这种损害。有趣的是，大脑的一些区域变得更加活跃，而其他区域，通常是附近的或相连的，却萎缩了。因此，大脑的可塑性似乎有助于保持大脑的功能，尽管与疾病有关的萎缩。这就解释了为什么大脑萎缩本身并不能帮助诊断抑郁症或痴呆症：患者和健康志愿者之间的扫描变化有很大的重叠。只有结合脑损伤的测量和代偿活动的数量，我们才能预测大脑功能的实际缺陷。这个一般的想法可以应用于痴呆症：最初大脑中负责记忆的区域（海马体）开始萎缩，记忆力受损，但人们仍然可以通过使用备忘录或日记等策略来弥补这一点。在疾病的后期，随着大脑的其他（额叶）部分受到影响，这些补偿机制失效，痴呆就开始了。同样，高质量的纤维连接似乎可以保护抑郁症高危人群不患这种疾病。我们已经开发了一种持续45分钟的磁共振扫描，它可以让我们收集有关大脑萎缩、白质完整性、血流、休息和工作的大脑网络的信息。白厅二期研究在过去25年里对7000名公务员进行了每年一次的调查，因此有了上述所有风险因素的信息，以及有关社会背景、锻炼和心理活动的其他信息。这类信息通常不能用于影像学研究，因为人们往往不能准确地记住这些信息。将来自800人的长期白厅II信息与我们敏感且信息丰富的MRI扫描序列相结合，将使我们能够检查风险因素和保护因素与大脑变化之间的联系。此外，它将帮助我们确定这些大脑变化对当前精神状态和表现的影响，回答有关抑郁症和痴呆症自然历史的重要问题。

With increasing age many people develop memory problems and depression. They are predicted by the same risk factors as heart attacks and strokes. We, therefore, believe that memory problems and depression in later life are found with brain changes typical of blood vessel disease. Typically, the brain white matter, where nerve fibre connections are located, is disturbed in its structure, and the grey matter shrinks, due to a loss of brain cells. Fortunately, the brain has a number of strategies to compensate for such damage. Interestingly, some areas of the brain become more active, as others, often nearby or connected, shrink. Brain plasticity thus seems to help keep the brain functioning, in spite of illness related shrinkage. This explains why brain shrinkage by itself does not help the diagnosis of depression or dementia: there is a large overlap in scan changes between patients and healthy volunteers. Only combining measures of brain damage and the amount of compensatory activity allows us to predict the actual deficit in brain function. This general idea can be applied to dementia: initially areas in the brain responsible for memory (the hippocampus) start to shrink, memory is impaired, but people can still compensate for this by using strategies, such as memos or diaries. Later in the illness, as other (frontal) parts of the brain are affected, these compensation mechanisms fail, and dementia sets in. Similarly, higher quality fibre connections in people of high risk of depression appear to protect them from actually developing the illness.We have developed a magnetic resonance scan lasting 45 minutes that allows us to collect information about brain shrinkage, white matter integrity, blood flow, resting and working brain networks. The Whitehall II study has examined 7000 civil servants over the last 25 years at yearly intervals, and has therefore information for all the risk factors mentioned above, as well as other information about social background, exercise and mental activity. This kind of information is usually not available for imaging studies, as people tend not to remember such information accurately. Combining long-term Whitehall II information from 800 people with our sensitive and informative MRI scanning sequence will allow us to examine the connection between risk factors and protective factors and brain changes. Furthermore, it will help us establish the effects of these brain changes on current mental state and performance, answering important questions about the natural history of depression and dementia.