Lehrer Steven, Rheinstein Peter H
Fermata Pharma, Inc, New York, NY, USA
Severn Health Solutions, Severna Park, MD, USA.
Am J Alzheimers Dis Other Demen. 2015 May;30(3):225-7. doi: 10.1177/1533317514545478. Epub 2014 Aug 5.
The Alzheimer's Association recently reported that a woman's estimated lifetime risk of developing Alzheimer's at age 65 is 1 in 6, compared to nearly 1 in 11 for a man (ie, female to male ratio 1.8). Based on female to male ratio, Alzheimer's disease could well be an autoimmune disorder. Like Alzheimer's, multiple sclerosis, an autoimmune inflammation of the central nervous system, has a female to male ratio of 2.3. Also based on female to male ratio, Alzheimer's resembles the autoimmune inflammatory disease rheumatoid arthritis, which has a female to male ratio of 2.7. The reasons for the female preponderance in autoimmune disease are unclear, but nonsteroidal anti-inflammatory drugs (NSAIDs) are widely and successfully employed to treat autoimmune anti-inflammatory disease and dramatically relieve symptoms. Moreover, oral NSAIDs consistently reduce the risk of Alzheimer's disease, although they have been totally ineffective as a treatment in multiple failed clinical trials. A basis for this failure might well be that the brain dose after oral administration is too small and not sufficiently early in the pathogenesis of the disorder. But NSAID brain dose could be significantly increased by delivering the NSAIDs intranasally.
阿尔茨海默病协会最近报告称,65岁女性患阿尔茨海默病的终生风险估计为六分之一,而男性为十一分之一(即女性与男性的比例为1.8)。基于女性与男性的比例,阿尔茨海默病很可能是一种自身免疫性疾病。与阿尔茨海默病一样,多发性硬化症是中枢神经系统的自身免疫性炎症,其女性与男性的比例为2.3。同样基于女性与男性的比例,阿尔茨海默病类似于自身免疫性炎症疾病类风湿性关节炎,其女性与男性的比例为2.7。自身免疫性疾病中女性占优势的原因尚不清楚,但非甾体抗炎药(NSAIDs)被广泛且成功地用于治疗自身免疫性抗炎疾病并显著缓解症状。此外,口服NSAIDs持续降低患阿尔茨海默病的风险,尽管在多次失败的临床试验中它们作为治疗方法完全无效。这种失败的一个原因很可能是口服给药后脑内剂量太小且在疾病发病机制中不够早。但通过鼻腔给药可以显著增加NSAIDs的脑内剂量。