Icahn School of Medicine at Mount Sinai, Department of Psychiatry, Box 1230, One Gustave L. Levy Place, New York, NY 10029, United States; James J. Peters Veterans Affairs Medical Center, Research & Development, Mail Code 151, 130 West Kingsbridge Road, Bronx, NY 10468, United States.
Icahn School of Medicine at Mount Sinai, Department of Psychiatry, Box 1230, One Gustave L. Levy Place, New York, NY 10029, United States.
Med Hypotheses. 2018 Jan;110:9-14. doi: 10.1016/j.mehy.2017.10.022. Epub 2017 Oct 31.
For some cardiovascular risk factors, association with risk for cognitive impairment observed in early old age is reduced, or paradoxically even reversed, as age of outcome increases. Successful cognitive aging is intact cognition in the oldest-old; we define resistant successful cognitive aging as successful cognitive aging despite high risk. The protected survivor model posits that a minority of the general population has a protective factor that mitigates the negative effect of a risk factor on successful cognitive aging for the unprotected majority. As age increases, differential failure rates increase the proportion of survivors with protection. Among the unprotected, the proportion with low risk increases, but among those with protection, high risk and low risk do not differ. Due to differential mortality, half the survivors are eventually protected - a majority among those with high risk, and a minority among those with low risk. According to the protective survivor model, an example of Simpson's paradox, the association of the risk factor with survival does not change within an individual, but the association in the surviving population changes as its age increases. We created quantitative illustrations of a simplified protected survivor model applied to successful cognitive aging to explain how the usual association of a risk factor with cognitive decline is reversed in the very old. In the illustrations, probability of subsequent survival was higher for survivors with high risk (mostly protected) than low risk (mostly not protected), an example of Simpson's paradox. Resistance to disease despite the presence of risk factors is consistent with the presence of countervailing protection. Based on the protected survivor model, we hypothesize that studies seeking protective factors against cognitive decline will be more effective by limiting a successful cognitive aging sample to resistant successful cognitive aging - to contrast with a sample without successful cognitive aging.
对于一些心血管风险因素，在老年早期观察到与认知障碍风险的关联随着结果年龄的增加而降低，或者相反，甚至逆转。成功的认知老化是指在最年长的人中保持认知完整；我们将有抵抗力的成功认知老化定义为尽管存在高风险，但认知仍成功老化。受保护的幸存者模型假设，少数一般人群具有保护因素，可以减轻风险因素对大多数不受保护的人群成功认知老化的负面影响。随着年龄的增加，差异失败率增加了具有保护作用的幸存者的比例。在未受保护的人群中，低风险的比例增加，但在具有保护作用的人群中，高风险和低风险之间没有差异。由于差异死亡率，最终有一半的幸存者受到保护——在高风险人群中占多数，在低风险人群中占少数。根据受保护的幸存者模型，这是辛普森悖论的一个例子，风险因素与生存的关联在个体内部不会改变，但在存活人群中的关联随着其年龄的增加而改变。我们创建了简化的受保护幸存者模型在成功认知老化中的定量说明，以解释为什么与认知能力下降相关的风险因素在非常年长的人中会逆转。在这些说明中，高风险（主要受保护）幸存者的后续生存概率高于低风险（主要不受保护）幸存者，这是辛普森悖论的一个例子。尽管存在风险因素，但对疾病的抵抗力与存在相反的保护作用是一致的。基于受保护的幸存者模型，我们假设，通过将成功认知老化样本限制在有抵抗力的成功认知老化——与没有成功认知老化的样本相比，寻找预防认知能力下降的保护因素的研究将更加有效。
