Clinical Neuroscience Research Unit and Brain Imaging Program, Department of Psychiatry, University of Vermont College of Medicine, Burlington, VT 05401, USA.
Pharmacol Biochem Behav. 2011 Aug;99(2):254-61. doi: 10.1016/j.pbb.2011.02.022. Epub 2011 Mar 5.
It is now possible to reevaluate the cholinergic hypothesis of age-related cognitive dysfunction based on a synthesis of new evidence from cholinergic stimulation studies and cognitive models. We propose that a change of functional circuitry that can be observed through a combination of pharmacologic challenge and functional neuroimaging is associated with age-related changes in cholinergic system functioning. Psychopharmacological manipulations using cholinergic agonists and antagonists have been consistent in replicating patterns of aging seen in functional imaging studies. In addition, studies of anticholinesterase drugs in patients with Alzheimer's disease and mild cognitive impairment show support for the proposal that cholinergic compensation causes alterations in task-related brain activity. Thus, the cholinergic hypothesis of age-related cognitive dysfunction deserves further consideration as new methodologies for evaluating its validity are increasingly being used. Future directions for testing hypotheses generated from this model are presented.
现在，基于胆碱能刺激研究和认知模型的新证据的综合，可以重新评估与年龄相关的认知功能障碍的胆碱能假说。我们提出，通过药物挑战和功能神经影像学相结合可以观察到的功能回路的变化与胆碱能系统功能的年龄相关变化有关。使用胆碱能激动剂和拮抗剂的精神药理学操作一直能够复制功能成像研究中观察到的衰老模式。此外，在阿尔茨海默病和轻度认知障碍患者中使用抗胆碱酯酶药物的研究支持这样的假设，即胆碱能代偿导致与任务相关的大脑活动发生变化。因此，随着越来越多的新方法被用于评估其有效性，与年龄相关的认知功能障碍的胆碱能假说值得进一步考虑。本文提出了从该模型中生成的假设的未来检验方向。
