Davis Matthew, O Connell Thomas, Johnson Scott, Cline Stephanie, Merikle Elizabeth, Martenyi Ferenc, Simpson Kit
Medicus Economics, LLC, Milton, MA, United States.
Takeda Pharmaceuticals International, Deerfield, IL, United States.
Curr Alzheimer Res. 2018;15(8):777-788. doi: 10.2174/1567205015666180119092427.
Alzheimer's Disease (AD) can be conceptualized as a continuum: patients progress from normal cognition to mild cognitive impairment (MCI) due to AD, followed by increasing severity of AD dementia. Prior research has measured transition probabilities among later stages of AD, but not for the complete spectrum.
To estimate annual progression rates across the AD continuum and evaluate the impact of a delay in MCI due to AD on the trajectory of AD dementia and clinical outcomes.
Patient-level longitudinal data from the National Alzheimer's Coordinating Center for n=18,103 patients with multiple visits over the age of 65 were used to estimate annual, age-specific transitional probabilities between normal cognition, MCI due to AD, and AD severity states (defined by Clinical Dementia Rating score). Multivariate models predicted the likelihood of death and institutionalization for each health state, conditional on age and time from the previous evaluation. These probabilities were used to populate a transition matrix describing the likelihood of progressing to a particular disease state or death for any given current state and age. Finally, a health state model was developed to estimate the expected effect of a reduction in the risk of transitioning from normal cognition to MCI due to AD on disease progression rates for a cohort of 65-year-old patients over a 35-year time horizon.
Annual transition probabilities to more severe states were 8%, 22%, 25%, 36%, and 16% for normal cognition, MCI due to AD, and mild/moderate/severe AD, respectively, at age 65, and increased as a function of age. Progression rates from normal cognition to MCI due to AD ranged from 4% to 10% annually. Severity of cognitive impairment and age both increased the likelihood of institutionalization and death. For a cohort of 100 patients with normal cognition at age 65, a 20% reduction in the annual progression rate to MCI due to AD avoided 5.7 and 5.6 cases of MCI due to AD and AD, respectively. This reduction led to less time spent in severe AD dementia health states and institutionalized, and increased life expectancy.
Transition probabilities from normal cognition through AD severity states are important for understanding patient progression across the AD spectrum. These estimates can be used to evaluate the clinical benefits of reducing progression from normal cognition to MCI due to AD on lifetime health outcomes.
阿尔茨海默病（AD）可被视为一个连续体：患者从正常认知发展为因AD导致的轻度认知障碍（MCI），随后AD痴呆的严重程度不断增加。先前的研究测量了AD后期阶段之间的转变概率，但未针对整个范围。
估计AD连续体中的年度进展率，并评估因AD导致的MCI延迟对AD痴呆轨迹和临床结局的影响。
使用来自国家阿尔茨海默病协调中心的患者水平纵向数据，该数据涉及n = 18,103名65岁以上多次就诊的患者，用于估计正常认知、因AD导致的MCI和AD严重程度状态（由临床痴呆评定量表评分定义）之间的年度、特定年龄的转变概率。多变量模型预测了每个健康状态下死亡和入住机构的可能性，以年龄和自上次评估以来的时间为条件。这些概率用于填充一个转变矩阵，该矩阵描述了对于任何给定的当前状态和年龄进展到特定疾病状态或死亡的可能性。最后，开发了一个健康状态模型，以估计降低因AD从正常认知转变为MCI的风险对一组65岁患者在35年时间范围内疾病进展率的预期影响。
在65岁时，正常认知、因AD导致的MCI以及轻度/中度/重度AD进展到更严重状态的年度转变概率分别为8%、22%、25%、36%和16%，并随年龄增加。因AD从正常认知进展到MCI的年率在4%至10%之间。认知障碍的严重程度和年龄均增加了入住机构和死亡的可能性。对于一组65岁时认知正常的100名患者，因AD进展到MCI的年率降低20%分别避免了5.7例和5.6例因AD导致的MCI和AD。这种降低导致在严重AD痴呆健康状态和入住机构的时间减少，并提高了预期寿命。
从正常认知到AD严重程度状态的转变概率对于理解患者在AD范围内的进展很重要。这些估计可用于评估降低因AD从正常认知进展到MCI对终身健康结局的临床益处。
