Banner Alzheimer's Institute, Phoenix, AZ, 85006, USA.
Ace Alzheimer Center Barcelona - Universitat Internacional de Catalunya, 08028, Barcelona, Spain.
Alzheimers Res Ther. 2024 Feb 15;16(1):36. doi: 10.1186/s13195-024-01399-7.
Understanding the relationship among changes in Clinical Dementia Rating (CDR), patient outcomes, and probability of progression is crucial for evaluating the long-term benefits of disease-modifying treatments. We examined associations among changes in Alzheimer's disease (AD) stages and outcomes that are important to patients and their care partners including activities of daily living (ADLs), geriatric depression, neuropsychiatric features, cognitive impairment, and the probabilities of being transitioned to a long-term care facility (i.e., institutionalization). We also estimated the total time spent at each stage and annual transition probabilities in AD.
The study included participants with unimpaired cognition, mild cognitive impairment (MCI) due to AD, and mild, moderate, and severe AD dementia in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) database. The associations among change in AD stages and change in relevant outcomes were estimated using linear mixed models with random intercepts. The probability of transitioning to long-term care facilities was modeled using generalized estimating equations. The total length of time spent at AD stages and annual transition probabilities were estimated with multistate Markov models.
The estimated average time spent in each stage was 3.2 years in MCI due to AD and 2.2, 2.0, and 2.8 years for mild, moderate, and severe AD dementia, respectively. The annual probabilities of progressing from MCI to mild, moderate, and severe AD dementia were 20, 4, and 0.7%, respectively. The incremental change to the next stage of participants with unimpaired cognition, MCI, and mild, moderate, and severe AD dementia (to death) was 3.2, 20, 26.6, 31, and 25.3%, respectively. Changes in ADLs, neuropsychiatric features, and cognitive measures were greatest among participants who transitioned from MCI and mild AD dementia to more advanced stages. Participants with MCI and mild and moderate AD dementia had increasing odds of being transitioned to long-term care facilities over time during the follow-up period.
The findings demonstrated that participants with early stages AD (MCI or mild dementia) were associated with the largest changes in clinical scale scores. Early detection, diagnosis, and intervention by disease-modifying therapies are required for delaying AD progression. Additionally, estimates of transition probabilities can inform future studies and health economic modeling.
了解临床痴呆评定量表（CDR）变化、患者结局和进展概率之间的关系对于评估疾病修饰治疗的长期益处至关重要。我们研究了阿尔茨海默病（AD）各阶段变化与患者及其护理伙伴关注的结局之间的关联，这些结局包括日常生活活动（ADL）、老年抑郁、神经精神特征、认知障碍以及进入长期护理机构（即机构化）的概率。我们还估计了 AD 中每个阶段的总时间和每年的过渡概率。
本研究纳入了认知正常、轻度认知障碍（MCI）归因于 AD 以及轻度、中度和重度 AD 痴呆的参与者，这些参与者来自国家阿尔茨海默病协调中心（NACC）统一数据集中（UDS）数据库。使用带有随机截距的线性混合模型来估计 AD 各阶段变化与相关结局变化之间的关联。使用广义估计方程对进入长期护理机构的概率进行建模。使用多状态马尔可夫模型估计 AD 各阶段的总时间和每年的过渡概率。
在 MCI 归因于 AD 中，估计的平均每个阶段持续时间为 3.2 年，而轻度、中度和重度 AD 痴呆分别为 2.2、2.0 和 2.8 年。从 MCI 进展到轻度、中度和重度 AD 痴呆的年概率分别为 20%、4%和 0.7%。认知正常、MCI 以及轻度、中度和重度 AD 痴呆患者进入下一个阶段的增量分别为 3.2%、20%、26.6%、31%和 25.3%。从 MCI 和轻度 AD 痴呆过渡到更高级阶段的患者，ADL、神经精神特征和认知测量的变化最大。随着时间的推移，患有 MCI 以及轻度和中度 AD 痴呆的患者被转入长期护理机构的几率增加。
研究结果表明，早期 AD（MCI 或轻度痴呆）患者与临床量表评分的最大变化相关。需要通过疾病修饰疗法进行早期发现、诊断和干预，以延缓 AD 的进展。此外，过渡概率的估计可以为未来的研究和健康经济学建模提供信息。
