Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA.
Department of Experimental Psychology, University of Oxford, Oxford, UK.
J Alzheimers Dis. 2020;75(4):1169-1180. doi: 10.3233/JAD-191268.
Alzheimer's disease (AD) is now understood to have a long preclinical phase in which pathology starts to accumulate in the absence of clinical symptoms. Identifying the temporal stages of accelerated cognitive decline in this phase may help in developing more sensitive neuropsychological tools for early screening of preclinical cognitive decline. Change-point analyses are increasingly used to characterize the temporal stages of accelerated cognitive decline in the preclinical stages of AD. However, statistical comparisons of change-points between specific cognitive measures have not been reported.
To characterize and compare the temporal stages of accelerated decline in performance on multiple cognitive tests in a sample of participants from the Baltimore Longitudinal Study on Aging (BLSA) who later developed AD.
165 older adults (baseline age range: 61.1-91.2) from the BLSA developed AD during follow-up. Linear and non-linear mixed models were fit for 11 cognitive measures to determine change-points in rates of decline before AD diagnosis. Bootstrapping was used to compare the timing of change-points across cognitive measures.
Change-points followed by accelerated decline ranged from 15.5 years (Standard Error (S.E.) = 1.72) for Card Rotations to 1.9 years (S.E. = 0.68) for the Trail-Making Test Part A before AD diagnosis. Accelerated decline in Card Rotations occurred significantly earlier than all other measures, including learning and memory measures.
Results suggest that visuospatial ability, as assessed by Card Rotations, may have the greatest utility as an early predictive tool in identifying preclinical AD.
阿尔茨海默病（AD）现在被认为有一个很长的临床前阶段，在此阶段，病理开始积累而没有临床症状。在这个阶段识别认知能力加速下降的时间阶段可能有助于开发更敏感的神经心理学工具，用于早期筛查临床前认知下降。变化点分析越来越多地用于描述 AD 临床前阶段认知能力加速下降的时间阶段。然而，尚未报道特定认知测量之间变化点的统计比较。
在后来发展为 AD 的巴尔的摩纵向衰老研究（BLSA）参与者样本中，对多项认知测试的表现进行特征化和比较加速下降的时间阶段。
BLSA 中有 165 名年龄较大的成年人（基线年龄范围：61.1-91.2）在随访期间发展为 AD。对 11 项认知测试进行线性和非线性混合模型拟合，以确定 AD 诊断前下降率的变化点。使用引导法比较认知测试之间变化点的时间。
AD 诊断前，变化点后的加速下降范围从卡片旋转的 15.5 年（标准误差（S.E.）= 1.72）到 Trail-Making Test 部分 A 的 1.9 年（S.E.）= 0.68）。卡片旋转的加速下降发生得明显早于所有其他测量值，包括学习和记忆测量值。
结果表明，卡片旋转评估的空间视觉能力可能作为识别临床前 AD 的早期预测工具具有最大的效用。
