Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
J Alzheimers Dis. 2013;35(4):823-32. doi: 10.3233/JAD-122146.
Risk factors for mild cognitive impairment (MCI) and dementia are often investigated without accounting for the competing risk of mortality, which can bias results and lead to spurious conclusions, particularly regarding protective factors. Here, we apply a semi-Markov modeling approach to 531 participants in the University of Kentucky Biologically Resilient Adults in Neurological Studies (BRAiNS) longitudinal cohort, over one-third of whom died without transitioning to a cognitively impaired clinical state. A semi-Markov approach enables a statistical study of clinical state transitions while accounting for the competing risk of death and facilitates insights into both the odds that a risk factor will affect clinical transitions as well as the age at which the transition to MCI or dementia will occur. Risk factors assessed in the current study were identified by matching those reported in the literature with the data elements collected on participants. The presence of Type II diabetes at baseline shortens the time it takes cognitively intact individuals to transition to MCI by seven years on average while use of estrogen replacement therapy at enrollment (baseline) decreases the time required to convert from MCI to dementia by 1.5 years. Finally, smoking and being overweight do not promote transitions to impaired states but instead hasten death without a dementia. In contrast, conventional statistical analyses based on Cox proportional hazards models fail to recognize diabetes as a risk, show that being overweight increases the risk of clinical MCI, and that high blood pressure at baseline increases the risk of a dementia.
发生轻度认知障碍（MCI）和痴呆的风险因素通常在没有考虑死亡竞争风险的情况下进行研究，这可能会使结果产生偏差，并导致虚假结论，尤其是在涉及保护因素时。在这里，我们对肯塔基大学具有神经生物学弹性的成年人纵向队列（BRAiNS）中的 531 名参与者应用半马尔可夫建模方法，其中超过三分之一的参与者在没有转变为认知障碍临床状态的情况下死亡。半马尔可夫方法能够在考虑死亡竞争风险的同时对临床状态转换进行统计研究，并有助于深入了解风险因素是否会影响临床转换的可能性，以及发生 MCI 或痴呆的转换年龄。目前研究中评估的风险因素是通过将文献中报告的风险因素与参与者收集的数据元素相匹配来确定的。与认知完整的个体相比，基线时存在 2 型糖尿病会使他们平均提前 7 年转变为 MCI，而在入组（基线）时使用雌激素替代疗法会使从 MCI 向痴呆的转变时间缩短 1.5 年。最后，吸烟和超重不会促进向受损状态的转变，而是在没有痴呆的情况下加速死亡。相比之下，基于 Cox 比例风险模型的传统统计分析未能识别出糖尿病作为风险因素，表明超重会增加临床 MCI 的风险，并且基线时的高血压会增加痴呆的风险。
