Barcelona Down Medical Center, Fundació Catalana Síndrome de Down, Barcelona, Spain.
Sant Pau Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau-Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
JAMA Netw Open. 2022 Aug 1;5(8):e2225573. doi: 10.1001/jamanetworkopen.2022.25573.
Alzheimer disease (AD) is the main medical problem in adults with Down syndrome (DS). However, the associations of age, intellectual disability (ID), and clinical status with progression and longitudinal cognitive decline have not been established.
To examine clinical progression along the AD continuum and its related cognitive decline and to explore the presence of practice effects and floor effects with repeated assessments.
DESIGN, SETTING, AND PARTICIPANTS: This is a single-center cohort study of adults (aged >18 years) with DS with different ID levels and at least 6 months of follow-up between November 2012 and December 2021. The data are from a population-based health plan designed to screen for AD in adults with DS in Catalonia, Spain. Individuals were classified as being asymptomatic, having prodromal AD, or having AD dementia.
Neurological and neuropsychological assessments.
The main outcome was clinical change along the AD continuum. Cognitive decline was measured by the Cambridge Cognitive Examination for Older Adults With Down Syndrome and the modified Cued Recall Test.
A total of 632 adults with DS (mean [SD] age, 42.6 [11.4] years; 292 women [46.2%]) with 2847 evaluations (mean [SD] follow-up, 28.8 [18.7] months) were assessed. At baseline, there were 436 asymptomatic individuals, 69 patients with prodromal AD, and 127 with AD dementia. After 5 years of follow-up, 17.1% (95% CI, 12.5%-21.5%) of asymptomatic individuals progressed to symptomatic AD in an age-dependent manner (0.6% [95% CI, 0%-1.8%] for age <40 years; 21.1% [95% CI, 8.0%-32.5%] for age 40-44 years; 41.4% [95% CI, 23.1%-55.3%] for age 45-49 years; 57.5% [95% CI, 38.2%-70.8%] for age ≥50 years; P < .001), and 94.1% (95% CI, 84.6%-98.0%) of patients with prodromal AD progressed to dementia with no age dependency. Cognitive decline in the older individuals was most common among those who progressed to symptomatic AD and symptomatic individuals themselves. Importantly, individuals with mild and moderate ID had no differences in longitudinal cognitive decline despite having different performance at baseline. This study also found practice and floor effects, which obscured the assessment of longitudinal cognitive decline.
This study found an association between the development of symptomatic AD and a high risk of progressive cognitive decline among patients with DS. These results support the need for population health plans to screen for AD-related cognitive decline from the fourth decade of life and provide important longitudinal data to inform clinical trials in adults with DS to prevent AD.
阿尔茨海默病（AD）是唐氏综合征（DS）成年患者的主要医学问题。然而，年龄、智力障碍（ID）和临床状况与进展和纵向认知下降的关联尚未确定。
检查 AD 连续体的临床进展及其相关的认知下降，并探讨重复评估时的练习效应和地板效应的存在。
设计、地点和参与者：这是一项单中心队列研究，纳入了具有不同 ID 水平的 18 岁以上的 DS 成年患者，在 2012 年 11 月至 2021 年 12 月期间至少有 6 个月的随访。数据来自一个基于人群的健康计划，旨在为加泰罗尼亚的 DS 成年患者筛查 AD。个体被分为无症状、前驱 AD 或 AD 痴呆。
神经学和神经心理学评估。
主要结局是 AD 连续体的临床变化。认知下降通过剑桥认知老年评估（Cambridge Cognitive Examination for Older Adults With Down Syndrome）和改良提示回忆测试（modified Cued Recall Test）进行测量。
共评估了 632 名 DS 成年患者（平均[标准差]年龄为 42.6[11.4]岁；292 名女性[46.2%]），共进行了 2847 次评估（平均[标准差]随访时间为 28.8[18.7]个月）。基线时，有 436 名无症状个体、69 名前驱 AD 患者和 127 名 AD 痴呆患者。在 5 年的随访后，无症状个体中有 17.1%（95%CI，12.5%-21.5%）以年龄依赖性的方式进展为有症状的 AD（年龄<40 岁的为 0.6%[95%CI，0%-1.8%]；年龄 40-44 岁的为 21.1%[95%CI，8.0%-32.5%]；年龄 45-49 岁的为 41.4%[95%CI，23.1%-55.3%]；年龄≥50 岁的为 57.5%[95%CI，38.2%-70.8%]；P<0.001），且 94.1%（95%CI，84.6%-98.0%）的前驱 AD 患者进展为痴呆，无年龄依赖性。在进展为有症状 AD 和有症状个体本身的老年人中，认知下降最为常见。重要的是，尽管基线表现不同，但 ID 轻度和中度的个体在纵向认知下降方面没有差异。本研究还发现了练习和地板效应，这掩盖了对纵向认知下降的评估。
本研究发现，DS 患者出现有症状 AD 与发生进行性认知下降的风险增加之间存在关联。这些结果支持人群健康计划从四十岁开始筛查 AD 相关认知下降的必要性，并提供了重要的纵向数据，为预防 AD 的 DS 成年患者临床试验提供信息。
