Joseph & Kathleen Bryan Alzheimer's Disease Research Center, Department of Neurology, Duke University Medical Center, Durham, North Carolina, USA.
Clin Pharmacol Ther. 2013 Feb;93(2):177-85. doi: 10.1038/clpt.2012.222. Epub 2012 Nov 7.
Curing Alzheimer's disease (AD) remains an elusive goal; indeed, it may even prove to be impossible, given the nature of the disease. Although modulating disease progression is an attractive target and will alleviate the burden of the most severe stages, this strategy will not reduce the prevalence of the disease itself. Preventing or (as described in this article) delaying the onset of cognitive impairment and AD will provide the greatest benefit to individuals and society by pushing the onset of disease into the later years of life. Because of the high variability in the age of onset of the disease, AD prevention studies that do not stratify participants by age-dependent disease risk will be operationally challenging, being large in size and of long duration. We present a composite genetic biomarker to stratify disease risk so as to facilitate clinical studies in high-risk populations. In addition, we discuss the rationale for the use of pioglitazone to delay the onset of AD in individuals at high risk.
治愈阿尔茨海默病（AD）仍然是一个难以实现的目标；事实上，鉴于这种疾病的性质，这甚至可能证明是不可能的。尽管调节疾病进展是一个有吸引力的目标，并将减轻最严重阶段的负担，但这种策略不会降低疾病本身的流行率。通过将疾病的发病推至生命后期，预防或（如本文所述）延迟认知障碍和 AD 的发病将为个人和社会带来最大的益处。由于疾病发病年龄的高度可变性，不按年龄相关疾病风险对参与者进行分层的 AD 预防研究在操作上具有挑战性，需要规模大和持续时间长。我们提出了一种综合遗传生物标志物来分层疾病风险，以便为高危人群的临床研究提供便利。此外，我们还讨论了使用吡格列酮延迟高危个体 AD 发病的原理。
