应对认知障碍，大脑另辟新径

患了老年痴呆症该怎么办呢？其实什么都记不住也挺幸福的。

新的研究数据给传统理论带来挑战。传统理论认为，老化的大脑，尤其是轻度认知障碍患者的大脑，无法经过记忆训练后，出现诸如活跃性增加这样的积极改变。

轻度认知障碍通常指阿尔茨海默病前期的一种精神状态，记忆训练可以帮助处于这种状态的人。但是，对这类人训练带来的改进并不比训练可能已经患有阿尔茨海默病的人更有效。

研究者们在分析1970年至2007年间的研究结果后做出了如此结论，并于一月十九日发表在《循证评论》上。

但是他们确实在这片文章中追加了这则让人感到庆幸的一段话：尽管已有的报告显示干预的效果有限，这并不意味着更长时间的，更密集的或者不同方式的干预可能没有效果，

另一项关于这个项目的研究结果目前由一组加拿大科学家发表在《六月脑科学》上。该研究不是一个用于测试记忆训练效果的随机对照试验，而是旨在探究记忆训练如何影响轻度认知损害患者大脑的一个记忆训练或者大脑扫描的研究。

该试验由蒙特利尔大学老年病学研究所所长Sylvie Belleville博士领导，包括30名年龄较老的人，其中15名患有轻度认知损害，另外15名健康的人作为对照组。（在之前的一项研究中，Belleville 和她的同事发现，尽管一些患有轻度认知障碍的人在训练一段时间后，看起来情况稳定甚至恢复到正常水平，但超过半数的患者病情在五年内发展到阿尔茨海默病。

被试者首先被要求记住指定词汇，在他们记忆这些词汇的过程中，研究者使用功能磁共振对他们进行大脑扫描。在接下来的六周里，对被试者进行记忆训练。他们学习到不同的助记符号和技巧以提高记忆编码和提取的能力。在记忆训练结束时，他们被要求记住指定的词汇，同时再对他们进行功能磁共振扫描。最后，将他们的扫描结果与对照组的扫描结果进行对比。

在给予记忆训练之前，当面对记忆任务时，实验组和对照组的人均显示出，参与典型的记忆活动时，前部区域和顶部区域活跃，以海马部分最为明显。当训练结束后给予记忆任务，这两组人的大脑同样在相同区域显示出了活跃性。

但需要补充的是，轻度记忆障碍的组显示出在脑部其他区域的活跃，比如，左颞叶（参与语言处理），右前额和顶部区域（参与空间和物体记忆），小脑和基底核（参与技能学习）。

这些研究结果因而表明记忆训练使患轻度记忆障碍的被试者的大脑能够使用新的此前不会用于记忆功能的大脑区域。正如Belleville和她的同事在他们的报告中指出，新使用的大脑区域包含在被试者学习到的各种可用的策略中。简而言之，记忆训练使轻度认知障碍引发的大脑活跃度从下降水平趋于正常水品。

Belleville和她的小组承认，一些重要的问题仍然需要回答。比如，研究者发现的大脑的改变仅发生在他们使用的特定的记忆训练项目时，或者其他类型的记忆训练也可能催发这些改变？

无论如何，他们的研究结果显示出早期阿尔兹海默症患者的大脑仍然具有灵活性，并且在他们的结论中提到“能够采用新的神经回路以完成记忆任务”。他们补充说，“这些结果同样为治疗记忆困难患者的潜在方案--认知训练，提供了经验支持”。

加利福尼亚大学精神病学教授Dilip Jeste, M.D和精神病科医生兼美国心理学会预选理事长San Diego在一次访问中表示，“显然，这些结果在确认成立之间，需要在不同的样本中得以重复验证。”

“然而，这些结果仍然让人兴奋，因为它们有助于挑战传统理念。传统理念认为，老化大脑尤其是轻度认知障碍患者的大脑不能出现积极的变化，出现诸如在非药物认知干预下的活跃性增加的现象。

Belleville告诉《精神病学新闻》， 她和她的小组将对该项目进行更多的研究。“其中一个研究将会是大规模的随机对照试验，对比认知干预和心理干预对轻度认知障碍患者的疗效，调查这些结果对轻度认知退化并逐步发展到痴呆的患者的长期影响和日常生活的影响。”

该项研究由魁北克健康研究基金，蒙特利尔大学老年病研究所，加拿大健康研究所共同资助。

Faced With Cognitive Impairment, Brain Enlists New Areas
Joan Arehart-Treichel
New data challenge the traditional notion that the aging brain, especially in people with mild cognitive impairment, is incapable of positive changes such as greater activation following memory training.

Memory training can help people with mild cognitive impairment—a psychological state often preceding Alzheimer's disease. But the improvements do not appear to be any better than those that could be obtained with, say, a discussion of art or politics.

This was the conclusion described by researchers on January 19 in the Cochrane Reviews after analyzing studies conducted on the subject between 1970 and 2007.

But they did include this more auspicious addendum: “This does not mean that longer, more intense, or different interventions might not be effective, but that those which have been reported thus far have only limited effect.”

Now another study on the subject has been published—in the June Brain—by a group of Canadian scientists. It was not a randomized, controlled trial designed to test the efficacy of memory training, but rather a memory-training/brain-scanning study intended to explore how memory training affects the brains of people with mild cognitive impairment.

The study, which was headed by Sylvie Belleville, Ph.D., director of the University of Montreal's Institute of Geriatrics, included 30 older adults—15 with mild cognitive impairment and 15 matched healthy controls. (In a previous study, Belleville and her colleagues had found that while some people with mild cognitive impairment seem to remain stable or even return to normal over time, more than half progress to Alzheimer's within five years.)

Subjects were first asked to remember certain words, and while they were remembering those words, fMRI scans were made of their brains. During the next six weeks, subjects were given memory training. They learned different mnemonics and techniques to promote memory encoding and retrieval. At the end of that time, they were again asked to remember certain words and again fMRI scans were made of their brains. Finally, the scan results for the mild cognitive impairment group were compared with those for the control group.

When presented with a memory challenge before memory training, both the mild cognitive impairment and control groups showed activation of frontal and parietal regions typically involved in memory, notably the hippocampus. And when presented with a memory challenge after training, both groups showed activation in the same areas as well.

But in addition, the mild cognitive impairment group showed activation in other brain areas—for example, the left temporal lobe (which is involved in language processing), the right prefrontal and parietal areas (involved in spatial and object memory), and the cerebellum and basal ganglia (involved in skill learning).

These findings thus suggested that memory training enabled the mild cognitive impairment subjects to recruit new brain areas that they would not have otherwise used in the remembering process. And as Belleville and her colleagues pointed out in their report, “The newly recruited brain regions are those involved in the types of strategies that participants learned to implement.” In brief, “Memory training normalizes the brain activation deficits associated with mild cognitive impairment.”

Some important questions remain to be answered, though, Belleville and her group acknowledged. For instance, are the brain changes that the researchers found specific to the particular memory training program they used, or would the changes also be triggered by other types of memory training programs?

In any event, their findings indicate that the brains of people with very early Alzheimer's are still quite plastic and “able to recruit new neural circuits to perform demanding memory tasks,” they concluded. “The findings also provide empirical support for the use of cognitive training as a potential treatment for people with memory difficulties,” they added.

“Obviously these findings need to be replicated in diverse samples before they can be considered as established,” Dilip Jeste, M.D., a professor of psychiatry at the University of California, San Diego, a geriatric psychiatrist, and president-elect of APA, said in an interview. “Nonetheless, the results are exciting as they help challenge the traditional notion that the aging brain, especially in people with mild cognitive impairment, is incapable of positive changes such as greater activation following cognitive nonpharmacological interventions.”

Belleville and her team will be conducting more research on this subject, she told Psychiatric News. “One will be a large-scale, randomized controlled trial comparing the efficacy of cognitive and psychosocial interventions in mild cognitive impairment and investigating their long-term effect on cognitive decline and progression to dementia and their effect in daily life.”

The study was funded by Research Health Funds of Quebec, the University of Montreal Institute of Geriatrics, and the Canadian Institutes for Health Research.

An abstract of “Training-Related Brain Plasticity in Subjects at Risk of Developing Alzheimer's Disease” is posted at <http://brain.oxfordjournals.org/content/134/6/1623.abstract>.