Department of Neurology, Mayo Clinic, Rochester, MN.
Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
Ann Neurol. 2021 Jun;89(6):1145-1156. doi: 10.1002/ana.26071. Epub 2021 Apr 6.
To operationalize the National Institute on Aging - Alzheimer's Association (NIA-AA) Research Framework for Alzheimer's Disease 6-stage continuum of clinical progression for persons with abnormal amyloid.
The Mayo Clinic Study of Aging is a population-based longitudinal study of aging and cognitive impairment in Olmsted County, Minnesota. We evaluated persons without dementia having 3 consecutive clinical visits. Measures for cross-sectional categories included objective cognitive impairment (OBJ) and function (FXN). Measures for change included subjective cognitive impairment (SCD), objective cognitive change (ΔOBJ), and new onset of neurobehavioral symptoms (ΔNBS). We calculated frequencies of the stages using different cutoff points and assessed stability of the stages over 15 months.
Among 243 abnormal amyloid participants, the frequencies of the stages varied with age: 66 to 90% were classified as stage 1 at age 50 but at age 80, 24 to 36% were stage 1, 32 to 47% were stage 2, 18 to 27% were stage 3, 1 to 3% were stage 4 to 6, and 3 to 9% were indeterminate. Most stage 2 participants were classified as stage 2 because of abnormal ΔOBJ only (44-59%), whereas 11 to 21% had SCD only, and 9 to 13% had ΔNBS only. Short-term stability varied by stage and OBJ cutoff points but the most notable changes were seen in stage 2 with 38 to 63% remaining stable, 4 to 13% worsening, and 24 to 41% improving (moving to stage 1).
The frequency of the stages varied by age and the precise membership fluctuated by the parameters used to define the stages. The staging framework may require revisions before it can be adopted for clinical trials. ANN NEUROL 2021;89:1145-1156.
为了使美国国家老龄化研究所-阿尔茨海默病协会（NIA-AA）的阿尔茨海默病 6 阶段临床进展连续体研究框架适用于异常淀粉样蛋白的个体，我们对 Mayo 诊所衰老研究进行了操作化。该研究是明尼苏达州奥姆斯特德县一项基于人群的衰老和认知障碍纵向研究。我们评估了没有痴呆症且连续 3 次就诊的个体。横断面分类的测量指标包括客观认知障碍（OBJ）和功能（FXN）。变化的测量指标包括主观认知障碍（SCD）、客观认知变化（ΔOBJ）和神经行为症状新发（ΔNBS）。我们使用不同的截止值计算了各阶段的频率，并评估了各阶段在 15 个月内的稳定性。
在 243 名异常淀粉样蛋白的参与者中，各阶段的频率随年龄而变化：50 岁时，66%至 90%被归类为第 1 阶段，但 80 岁时，24%至 36%为第 1 阶段，32%至 47%为第 2 阶段，18%至 27%为第 3 阶段，1%至 3%为第 4 至 6 阶段，3%至 9%为不确定阶段。大多数第 2 阶段的参与者仅因异常 ΔOBJ 而被归类为第 2 阶段（44%-59%），而仅有 11%至 21%仅有 SCD，9%至 13%仅有 ΔNBS。短期稳定性因阶段和 OBJ 截止值而异，但最明显的变化发生在第 2 阶段，其中 38%至 63%保持稳定，4%至 13%恶化，24%至 41%改善（转移到第 1 阶段）。
阶段的频率随年龄而变化，并且由于用于定义阶段的参数的精确成员资格也会波动。在该框架可以用于临床试验之前，可能需要对其进行修订。
