Medical Decision Modeling Inc., Indianapolis, IN, USA.
Alzheimers Dement. 2012 Jan;8(1):31-8. doi: 10.1016/j.jalz.2011.05.2415.
Advances in screening and treatment are needed to mitigate increasing prevalence of dementia due to Alzheimer's disease (DAT). Current proposals to revise Alzheimer's disease (AD) diagnostic criteria incorporate diagnostic biomarkers. Such revisions would allow identification of persons with AD pathology before the onset of dementia. The population-level impact of screening for preclinical AD and treating with a disease-modifying agent is important when evaluating new biomarkers and medications.
A published computer simulation model assigned AD-related event times, such that delays in disease progression due to therapy effectiveness can be estimated for a preclinical AD cohort. Attributes such as screening sensitivity/specificity, treatment efficacy, age at first screening, and rescreening intervals were varied. Outcomes included incident mild cognitive impairment (MCI-AD), incident DAT, and number of patients recommended for treatment.
One-time screening at age 65 years, 50% efficacy, and literature-based proxy persistence rates yielded 12.4% incidence of MCI-AD and 0.9% decrease in DAT incidence from base case of no screening/treatment. Modest reductions in incident MCI-AD and DAT were observed with more sensitive testing. Reducing specificity yielded greater reductions in MCI-AD and DAT cases, albeit by treating more patients. Probabilistic sensitivity analysis predicted that for a cohort of patients aged 65 years, the number that needed to be treated to avoid one AD case was 11.6 (range: 5.7-104).
The reduction in MCI-AD and DAT depends on initial screening age, screening frequency, and specificity. When considering population-level impact of screening-treatment, the effect of these parameters on incidence would need to be weighed against the number of individuals screened and treated.
由于阿尔茨海默病（DAT）导致痴呆症的患病率不断上升，因此需要在筛查和治疗方面取得进展。目前，对阿尔茨海默病（AD）诊断标准进行修订的建议包括诊断生物标志物。这种修订将允许在痴呆症发作之前识别出患有 AD 病理学的人。当评估新的生物标志物和药物时，筛查临床前 AD 并使用具有改变疾病作用的药物进行治疗对人群水平的影响非常重要。
已发表的计算机模拟模型分配了 AD 相关事件时间，以便可以估计临床前 AD 队列中由于治疗效果而导致疾病进展的延迟。诸如筛查敏感性/特异性、治疗效果、首次筛查年龄和重新筛查间隔等属性发生了变化。结果包括轻度认知障碍（MCI-AD）的发生率、DAT 的发生率以及建议进行治疗的患者人数。
在 65 岁时进行一次性筛查、50%的疗效和基于文献的代理持续率，可使 MCI-AD 的发病率为 12.4%，而不进行筛查/治疗的基础病例中 DAT 的发病率则降低了 0.9%。通过更敏感的测试观察到 MCI-AD 和 DAT 发生率的适度降低。降低特异性会导致 MCI-AD 和 DAT 病例的更大减少，尽管是通过治疗更多的患者。概率敏感性分析预测，对于 65 岁的患者队列，需要治疗的人数为 11.6（范围：5.7-104），以避免出现一例 AD 病例。
MCI-AD 和 DAT 的减少取决于初始筛查年龄、筛查频率和特异性。在考虑筛查治疗的人群水平影响时，需要权衡这些参数对发病率的影响与筛查和治疗的人数。
