Potential for intermittent stimulation of nucleus basalis of Meynert to impact treatment of alzheimer's disease.
Potential for intermittent stimulation of nucleus basalis of Meynert to impact treatment of alzheimer's disease.
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DOI：
10.1080/19420889.2017.1389359
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发表时间：
2017-01-01
影响因子：
--
通讯作者：
Liu, Ruifeng
中科院分区：
文献类型：
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作者：
Blake, David T;Terry, Alvin V;Liu, Ruifeng
在衰老和阿尔茨海默病中，大脑的胆碱能唤醒通路与大脑的执行功能同时下降。治疗阿尔茨海默病的一线和目前最有效的方法是使用胆碱酯酶抑制剂，它以剂量依赖的方式，在治疗的头几个月里改善认知能力下降的症状，然后再进一步下降。我们最近发现间歇性深部脑刺激Meynert基底核可以改善年轻成年猴子的工作记忆功能，并且这种改善依赖于胆碱能功能。在几分钟内，猴子在一段时间内记忆刺激的能力有所提高。几个月后，即使在没有刺激的情况下，猴子也能更好地完成工作记忆任务。在这里，我们展示了我们的猴子群体的历史数据，其中有二十多只动物在执行相同的行为任务时达到渐近表现水平。利用基于历史数据的分布，我们估计，在刺激开始后的头几个月，接受间歇性刺激的猴子的表现水平超过了同龄动物的32- 44%。讨论了早期阿尔茨海默病患者认知功能平行增加的含义。
The brain's cholinergic arousal pathways decline in parallel with the brain's executive functions in aging and Alzheimer's Disease. The frontline and currently most effective approach to treating Alzheimer's disease is the administration of cholinesterase inhibitors, which, in a dose dependent manner, improve the symptoms of cognitive decline over the first months of treatment before further decline occurs. We recently showed that intermittent deep brain stimulation of the nucleus basalis of Meynert improves working memory function in young adult monkeys, and that this improvement depended on cholinergic function. Within minutes, the monkeys' ability to remember stimuli over a delay period improved. Over months, the monkeys performed the working memory task better even in the absence of stimulation. Here, we show historical data from our monkey colony in which more than two dozen animals have performed the same behavioral task to asymptotic performance levels. Using a distribution based on our historical data, we estimate that the monkeys receiving intermittent stimulation leapt over the performance level of 32-44 percent of peer animals in the first several months after stimulation was initiated. Implications for a parallel increase in cognitive function for early Alzheimer's patients are discussed.