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P. Murali Doraiswamy discusses recent breakthroughs in diagnosing Alzheimer's disease and what everyone can do to postpone the onset of memory loss.
P. Murali Doraiswamy is the head of biological psychiatry at Duke University and is a Senior Fellow at Duke's Center for the Study of Aging. He's also the co-author of The Alzheimer's Action Plan, a guide for patients and family members struggling with the disease. Mind Matters editor Jonah Lehrer chats with Doraiswamy about recent advances in Alzheimer's research and what people can do to prevent memory loss.
LEHRER: What do you think are the biggest public misconceptions of Alzheimer's disease?
DORAISWAMY: The two biggest misconceptions are "It's just aging" and "It's untreatable, so we should just leave the person alone." Both of these misconceptions are remnants of an outdated view that hinders families from getting the best diagnosis and best care. They were also one of the main reasons I wanted to write this book.
Although old age is the single biggest risk for dementia, Alzheimer's is not a normal part of aging. Just ask any family member who has cared for a loved one with Alzheimer's and they will tell you how different the disease is from normal aging. Alzheimer's can strike people as young as their forties; there are some half a million individuals in the United States with early-onset dementia. Recent research has pinpointed disruptions in specific memory networks in Alzheimer's patients, such as those involving the posteromedial cortex and medial temporal lobe, that appear distinct from normal aging.
The larger point is that while Alzheimer's is still incurable it's not untreatable. There are four FDA-approved medications available for treating Alzheimer symptoms and many others in clinical trials. Strategies to enhance general brain and mental wellbeing can also help people with Alzheimer's. That's why early detection is so important.
LEHRER: Given the rapid aging of the American population - by 2050, the Alzheimer's Association estimates there will be a million new cases annually - what are the some preventative steps that people can take to prevent or delay the onset of the disease?
DORAISWAMY: Unfortunately, there isn't yet a magic bullet for prevention. You can pop the most expensive anti-aging pills, drink the best red wine, and play all the brain games that money can buy, and you still might get Alzheimer's. While higher education is clearly protective, even Nobel Laureates have been diagnosed with the disease, although it's likely their education helped them stave off the symptoms for a little bit.
My approach is more pragmatic - it's about recognizing risks and designing your own brain health action plan. The core of our program is to teach people about the growing links between cardiovascular markers （blood pressure, blood sugar, body weight and BMI, blood cholesterol, C-reactive protein） and brain health. A population study from Finland has developed a fascinating scale that can predict 20-year risk for dementia – sort of a brain aging speedometer. Obesity, smoking, lack of physical activity, high blood pressure, and high cholesterol are some of the culprits this study identified. So keeping these under control is crucial.
Depression is another risk factor for memory loss, so managing stress and staying socially connected is also important. B vitamins may prevent dementia in those who are deficient and there are some simple blood tests that can detect this. For the vast majority of people, however, there are no prescription medications that have been proven to prevent dementia. This means that a brain-healthy lifestyle is really our best bet for delaying the onset of memory loss.
In the near future we will likely have prevention plans that are personalized based on genetic, metabolic and neurological information. In familial Alzheimer's disease, pre-implantation genetic diagnosis has already been used to successfully deliver babies free of a deadly Alzheimer causing mutation-though only time will tell if deleting such dementia risk genes in humans has other consequences.
LEHRER: Your book talks about a new technique that allows doctors to image amyloid plaques in the brain. How will these change the diagnosis of the disease?
DORAISWAMY: Amyloid PET scans are in the late stages of validation testing to see if they can improve the accuracy of clinical diagnosis. The Alzheimer's brain is defined by beta-amyloid plaques and tangles but, at present, these can only be definitively diagnosed with an autopsy. If an amyloid PET scan is "plaque negative" that will tell a doctor that Alzheimer's is unlikely to be the diagnosis and help reassure the family. Early findings suggest that people who carry risk genes are more likely to have plaque positive scans even before they develop symptoms - suggesting that the scans could possibly be useful for predicting future risk. If true, this might eventually lead to a change in diagnostic terminology where "preclinical" Alzheimer's is diagnosed purely based on biomarker and scan findings long before memory symptoms start. Therapies to treat Alzheimer's by blocking amyloid plaques are already in trials but are currently given blindly to patients without knowing their brain plaque status-raising their risk for side effects and treatment failure. So this scan may also help drug development by helping select the most appropriate subjects for treatment and then monitoring treatment effects. Amyloid accumulation with aging is seen in many animal species and the scan offers us a tool to study what role plaque plays in normal brain aging. So this could do for the brain what colonoscopy did for the gut!
LEHRER: Will science ever find a cure for Alzheimer's?
DORAISWAMY: It's an incredibly tough puzzle to crack but the pace of research is so great that new drug targets are being reported daily. I think a form of cure is more likely to come from delaying the onset rather than by growing new brain cells to repair lost tissue. Realistically speaking there are several fundamental questions we don't fully understand and have yet to answer: What causes the disease? Why do plaques and tangles form? Why are the memory centers the first to be destroyed? On the positive side, there are several dozen drugs in clinical trials.
LEHRER: What recent scientific advances in treating or understanding Alzheimer's are you most excited about?
DORAISWAMY: I'm most excited about diagnostic advances. By using a combination of biomarkers, genetic tests and new brain scans, we are inching very close to predicting not only who will develop Alzheimer's but the exact age when they may start developing symptoms. This offers huge opportunities for conducting prevention trials. Of course, it also brings a whole host of ethical challenges, since our diagnostic and predictive abilities are advancing far faster than our ability to prevent Alzheimer's.
On the treatment side, there are several developments that I am excited about. The interactions between vascular disease and memory loss suggest that at least some aspects of Alzheimer's may be modifiable through diet and exercise. Dimebon, a drug that improves mitochondrial function, has yielded promising results and is in final stages of testing. In addition, therapeutic strategies which target the brain's own ability to repair itself – for example, by delivering nerve growth factor through viral vectors – are in clinical trials. Until we have a cure, however, it's really important to focus on improving the quality of life of people with Alzheimer's.
P.Murali Doraiswamy 讨论了最近阿尔兹海默症诊断方面的进展，以及人们可以做些什么以延迟记忆衰退的发生。
P.Murali Doraiswamy是杜克大学生物精神分析学的带头人，也是杜克大学衰老研究中心的高级研究员。同时他也是《阿尔兹海默症行动计划》的作者之一，该书为阿尔兹海默症患者以及他们的亲属提供了与此病抗争的导向。Mind Matters（心灵问题）的编辑Jonah Lehrer与Doraiswamy谈了关于最近阿尔兹海默症研究的最新进展，以及人们可以如何防止记忆衰退的问题。
LEHRER:你认为，什么是公众对于阿尔兹海默症最大的误区？
DORAISWAMY:最大的两个误区是，"这只是衰老",以及"这是不可治疗的，所以我们只能随那些患者去。"这两点误区都是过时观点的残留，它阻碍了家庭对疾病做出最佳的诊断和照料。这也是我写这本书很重要的原因之一。
尽管高龄是唯一的引起失忆的最大风险，阿尔兹海默症却不是衰老的正常组成部分。问任何一个照顾过患有阿尔兹海默症的挚爱的亲属，他们都会告诉你，这种疾病与通常的衰老有多么不同。阿尔兹海默症能发生在像四十多岁这样年纪的年轻人身上；美国大约有五十万人有早发性的失忆。最近的研究指出，阿尔兹海默症患者某些记忆通路出现了毁坏，例如中后皮层和颞叶中回中的记忆通路与通常的衰老者看起来有差异。
更重要的一点是，尽管阿尔兹海默症仍然是无法治愈的，但并不是无法治疗的。现在有四种FDA认可的药物可用于治疗阿尔兹海默症的症状，还有许多其他临床的方法。提升整体脑功能和心理机能的方法也对阿尔兹海默症患者有帮助。这就是早发现的重要性。
LEHRER:在美国人口急剧老龄化的背景下--到2050年，阿尔兹海默症协会估计，每年将出现100万例新病例--人们可以做些什么预防性的措施来预防或者延迟这种疾病的发生呢？
DORAISWAMY:很不幸，现在还没有一种预防的灵丹妙药。你可以拿到最贵的抗衰老药片，喝最好的红酒，玩所有用钱可以买到的脑力游戏，然而你仍然可能得阿尔兹海默症。即使受更高级的教育显然是有预防作用的，但即使是诺贝尔奖获得者也有被诊断为阿尔兹海默症的，尽管他们的教育很有可能帮助他们小小地减轻了症状。
我做的更实用些--这是关于认识到风险并且设计你自己独特的脑健康行动计划。我们行动的核心是教人们心血管系统指标（血压、血糖、体重和身高体重指数、血液胆固醇含量、C反应蛋白）与脑健康之间密切的联系。一项芬兰的人口学研究给出了一个引人注目的量表，能够预计20年罹患失忆症的风险，即一种大脑衰老的速度计。肥胖、吸烟、身体缺乏活动、高血压和高胆固醇是这项研究确定的一些罪魁祸首。所以严格控制这些是相当关键的。
抑郁是另一个记忆衰退的可能诱因，所以压力管理与保持社会交往是重要的。对于缺乏者而言，维生素B可能能防止记忆丧失，而简单的血液检测就能检测出来。然而对于大多数人而言，并没有被证明有效的药物处方可以预防记忆丧失。这说明，脑健康的生活方式确实是我们最好的延迟记忆衰退的赌注。
在不远的将来，我们可能会有一些个性化的基于基因、新陈代谢和神经信息的预防计划。在家族性的阿尔兹海默症中，胚胎植入前的基因诊断已经成功地应用于接生婴儿，使之免受阿尔兹海默症造成的致命损伤--尽管只有时间才知道，删除这些人类高危记忆丧失基因是否会造成其他结果。
LEHRER:你的书介绍了一种新技术，医生可以成像脑中的淀粉样蛋白斑块。这些将如何改变疾病的诊断？
DORAISWAMY:淀粉PET扫描正处于验证它是否能够提高临床诊断准确率的后期阶段。阿尔兹海默症大脑的特征是β-淀粉样蛋白板块和神经纤维纠缠，但目前为止，这只能在验尸中才能被准确诊断。如果淀粉PET扫描是"斑块隐形"的，那这就告诉一声，阿尔兹海默症的可能性不大，可以使家人安心。早期的发现说明，带有高危基因的人更可能有阳性的扫描结果，即使他们还没有发生症状，这说明，扫描可能在预测将来疾病风险上是有用的。如果是真的话，这最终可能导向诊断术语的改变，"前临床"阿尔兹海默症的诊断是完全基于生物标志物和扫描结果，切远在记忆症状出现之前的。阻断病人淀粉样蛋白板块的阿尔兹海默症疗法已经在尝试中，但是目前比较盲目，并不清楚病人大脑斑块的具体状况，而这家中了副作用和治疗失败发生的可能性。所以，通过选择最合适的治疗对象以及监控治疗效果，这个扫描的发展也可能会带来药物的发展。随年龄增长的淀粉积累在很多动物中都有发现，而扫描给我们提供了一种研究方法，研究斑块在正常大脑衰老过程中的作用。这对大脑所做的就像结肠镜检查对肠子所做的一样！
LEHRER:科学会发现一条治愈阿尔兹海默症的道路吗？
DORAISWAMY:这是一个困难得难以想象的谜团，但是研究的步伐相当快，每天都有报道发现了新的药物靶向。我想那种治愈应该更像是推迟发生，而不是产生新的脑细胞替代死亡的神经纤维。现实地说，我们仍然有几个基础性的问题还没有完全理解，需要继续回答：什么导致了这种疾��？为什么会产生斑块和纠缠？为什么记忆中心会首先被摧毁？从积极的方面说，现在正有几十种药物处于临床试验阶段。
LEHRER:最让你感到兴奋的治疗或者认识阿尔兹海默症的科学进展是什么？
DORAISWAMY:我最感兴趣的是诊断的进展。结合地运用生物学标志物、基因检测和新型的脑成像技术，我们正在越来越接近地预测不仅是谁会得阿尔兹海默症，还有他们产生症状的确切年龄。这给我们提供了许多机会采取预防措施。当然，这也会带来整体的伦理挑战，因为我们的诊断和预测能力发展得远远快于预防阿尔兹海默症。
在治疗方面，我对几项发展非常有兴趣。心血管疾病与记忆衰退之间的交互作用说明，至少在某些方面阿尔兹海默症的病情可以因为饮食和锻炼而变化。Dimebon是一种改善线粒体功能的药物，产生了可喜的结果，目前正处在试验的最后阶段。另外，旨在大脑修复自身功能的治疗策略--例如，通过过滤性病毒运送体运送神经生长素--正处在临床试验中。然而，直到我们找到治愈的方法之前，我们须关注提高阿尔兹海默症患者的生活质量。
