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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 Both of these misconceptions are remnants of an outdated view that hinders families from getting the best diagnosis and best care.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 討論了最近阿爾茲海默癥診斷方面的進展，以及人們可以做些什么以延遲記憶衰退的發(fā)生。
P.Murali Doraiswamy是杜克大學(xué)生物精神分析學(xué)的帶頭人，也是杜克大學(xué)衰老研究中心的高級研究員。同時他也是《阿爾茲海默癥行動計劃》的作者之一，該書為阿爾茲海默癥患者以及他們的親屬提供了與此病抗?fàn)幍膶?dǎo)向。Mind Matters（心靈問題）的編輯Jonah Lehrer與Doraiswamy談了關(guān)于最近阿爾茲海默癥研究的最新進展，以及人們可以如何防止記憶衰退的問題。
LEHRER:你認為，什么是公眾對于阿爾茲海默癥最大的誤區(qū)？
DORAISWAMY:最大的兩個誤區(qū)是，"這只是衰老",以及"這是不可治療的，所以我們只能隨那些患者去。"這兩點誤區(qū)都是過時觀點的殘留，它阻礙了家庭對疾病做出最佳的診斷和照料。這也是我寫這本書很重要的原因之一。
盡管高齡是唯一的引起失憶的最大風(fēng)險，阿爾茲海默癥卻不是衰老的正常組成部分。問任何一個照顧過患有阿爾茲海默癥的摯愛的親屬，他們都會告訴你，這種疾病與通常的衰老有多么不同。阿爾茲海默癥能發(fā)生在像四十多歲這樣年紀的年輕人身上；美國大約有五十萬人有早發(fā)性的失憶。最近的研究指出，阿爾茲海默癥患者某些記憶通路出現(xiàn)了毀壞，例如中后皮層和顳葉中回中的記憶通路與通常的衰老者看起來有差異。
更重要的一點是，盡管阿爾茲海默癥仍然是無法治愈的，但并不是無法治療的�，F(xiàn)在有四種FDA認可的藥物可用于治療阿爾茲海默癥的癥狀，還有許多其他臨床的方法。提升整體腦功能和心理機能的方法也對阿爾茲海默癥患者有幫助。這就是早發(fā)現(xiàn)的重要性。
LEHRER:在美國人口急劇老齡化的背景下--到2050年，阿爾茲海默癥協(xié)會估計，每年將出現(xiàn)100萬例新病例--人們可以做些什么預(yù)防性的措施來預(yù)防或者延遲這種疾病的發(fā)生呢？
DORAISWAMY:很不幸，現(xiàn)在還沒有一種預(yù)防的靈丹妙藥。你可以拿到最貴的抗衰老藥片，喝最好的紅酒，玩所有用錢可以買到的腦力游戲，然而你仍然可能得阿爾茲海默癥。即使受更高級的教育顯然是有預(yù)防作用的，但即使是諾貝爾獎獲得者也有被診斷為阿爾茲海默癥的，盡管他們的教育很有可能幫助他們小小地減輕了癥狀。
我做的更實用些--這是關(guān)于認識到風(fēng)險并且設(shè)計你自己獨特的腦健康行動計劃。我們行動的核心是教人們心血管系統(tǒng)指標(biāo)（血壓、血糖、體重和身高體重指數(shù)、血液膽固醇含量、C反應(yīng)蛋白）與腦健康之間密切的聯(lián)系。一項芬蘭的人口學(xué)研究給出了一個引人注目的量表，能夠預(yù)計20年罹患失憶癥的風(fēng)險，即一種大腦衰老的速度計。肥胖、吸煙、身體缺乏活動、高血壓和高膽固醇是這項研究確定的一些罪魁禍?zhǔn)�。所以嚴格控制這些是相當(dāng)關(guān)鍵的。
抑郁是另一個記憶衰退的可能誘因，所以壓力管理與保持社會交往是重要的。對于缺乏者而言，維生素B可能能防止記憶喪失，而簡單的血液檢測就能檢測出來。然而對于大多數(shù)人而言，并沒有被證明有效的藥物處方可以預(yù)防記憶喪失。這說明，腦健康的生活方式確實是我們最好的延遲記憶衰退的賭注。
在不遠的將來，我們可能會有一些個性化的基于基因、新陳代謝和神經(jīng)信息的預(yù)防計劃。在家族性的阿爾茲海默癥中，胚胎植入前的基因診斷已經(jīng)成功地應(yīng)用于接生嬰兒，使之免受阿爾茲海默癥造成的致命損傷--盡管只有時間才知道，刪除這些人類高危記憶喪失基因是否會造成其他結(jié)果。
LEHRER:你的書介紹了一種新技術(shù)，醫(yī)生可以成像腦中的淀粉樣蛋白斑塊。這些將如何改變疾病的診斷？
DORAISWAMY:淀粉PET掃描正處于驗證它是否能夠提高臨床診斷準(zhǔn)確率的后期階段。阿爾茲海默癥大腦的特征是β-淀粉樣蛋白板塊和神經(jīng)纖維糾纏，但目前為止，這只能在驗尸中才能被準(zhǔn)確診斷。如果淀粉PET掃描是"斑塊隱形"的，那這就告訴一聲，阿爾茲海默癥的可能性不大，可以使家人安心。早期的發(fā)現(xiàn)說明，帶有高�；虻娜烁赡苡嘘栃缘膾呙杞Y(jié)果，即使他們還沒有發(fā)生癥狀，這說明，掃描可能在預(yù)測將來疾病風(fēng)險上是有用的。如果是真的話，這最終可能導(dǎo)向診斷術(shù)語的改變，"前臨床"阿爾茲海默癥的診斷是完全基于生物標(biāo)志物和掃描結(jié)果，切遠在記憶癥狀出現(xiàn)之前的。阻斷病人淀粉樣蛋白板塊的阿爾茲海默癥療法已經(jīng)在嘗試中，但是目前比較盲目，并不清楚病人大腦斑塊的具體狀況，而這家中了副作用和治療失敗發(fā)生的可能性。所以，通過選擇最合適的治療對象以及監(jiān)控治療效果，這個掃描的發(fā)展也可能會帶來藥物的發(fā)展。隨年齡增長的淀粉積累在很多動物中都有發(fā)現(xiàn)，而掃描給我們提供了一種研究方法，研究斑塊在正常大腦衰老過程中的作用。這對大腦所做的就像結(jié)腸鏡檢查對腸子所做的一樣！
LEHRER:科學(xué)會發(fā)現(xiàn)一條治愈阿爾茲海默癥的道路嗎？
DORAISWAMY:這是一個困難得難以想象的謎團，但是研究的步伐相當(dāng)快，每天都有報道發(fā)現(xiàn)了新的藥物靶向。我想那種治愈應(yīng)該更像是推遲發(fā)生，而不是產(chǎn)生新的腦細胞替代死亡的神經(jīng)纖維�，F(xiàn)實地說，我們?nèi)匀挥袔讉�基礎(chǔ)性的問題還沒有完全理解，需要繼續(xù)回答：什么導(dǎo)致了這種疾�。繛槭裁磿a(chǎn)生斑塊和糾纏？為什么記憶中心會首先被摧毀？從積極的方面說，現(xiàn)在正有幾十種藥物處于臨床試驗階段。
LEHRER:最讓你感到興奮的治療或者認識阿爾茲海默癥的科學(xué)進展是什么？
DORAISWAMY:我最感興趣的是診斷的進展。結(jié)合地運用生物學(xué)標(biāo)志物、基因檢測和新型的腦成像技術(shù)，我們正在越來越接近地預(yù)測不僅是誰會得阿爾茲海默癥，還有他們產(chǎn)生癥狀的確切年齡。這給我們提供了許多機會采取預(yù)防措施。當(dāng)然，這也會帶來整體的倫理挑戰(zhàn)，因為我們的診斷和預(yù)測能力發(fā)展得遠遠快于預(yù)防阿爾茲海默癥。
在治療方面，我對幾項發(fā)展非常有興趣。心血管疾病與記憶衰退之間的交互作用說明，至少在某些方面阿爾茲海默癥的病情可以因為飲食和鍛煉而變化。Dimebon是一種改善線粒體功能的藥物，產(chǎn)生了可喜的結(jié)果，目前正處在試驗的最后階段。另外，旨在大腦修復(fù)自身功能的治療策略--例如，通過過濾性病毒運送體運送神經(jīng)生長素--正處在臨床試驗中。然而，直到我們找到治愈的方法之前，我們須關(guān)注提高阿爾茲海默癥患者的生活質(zhì)量。
