Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA, USA; Division of Sleep Medicine, Department of Medicine, Harvard Medical School, Boston, MA, USA.
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Neurobiol Aging. 2019 Nov;83:21-30. doi: 10.1016/j.neurobiolaging.2019.08.023. Epub 2019 Aug 30.
Many outputs from healthy neurophysiological systems including motor activity display nonrandom fluctuations with fractal scaling behavior as characterized by similar temporal fluctuation patterns across a range of time scales. Degraded fractal regulation predicts adverse consequences including Alzheimer's dementia. We examined longitudinal changes in the scaling behavior of motor activity fluctuations during the progression of Alzheimer's disease (AD) in 1068 participants in the Rush Memory and Aging Project. Motor activity of up to 10 days was recorded annually for up to 13 years. Cognitive assessments and clinical diagnoses were administered annually in the same participants. We found that fractal regulation gradually degraded over time (p < 0.0001) even during the stage with no cognitive impairment. The degradation rate was more than doubled after the diagnosis of mild cognitive impairment and more than doubled further after the diagnosis of Alzheimer's dementia (p's ≤ 0.0005). Besides, the longitudinal degradation of fractal regulation significantly correlated with the decline in cognitive performance throughout the progression from no cognitive impairment to mild cognitive impairment, and to AD (p < 0.001). All effects remained the same in subsequent sensitivity analyses that included only 255 decedents with autopsy-confirmed Alzheimer's pathology. These results indicate that the progression of AD accelerates fractal degradation and that fractal degradation may be an integral part of the process of AD.
许多健康神经生理系统的输出，包括运动活动，显示出非随机波动，具有分形标度行为特征，即在一系列时间尺度上具有相似的时间波动模式。分形调节的恶化预示着不良后果，包括阿尔茨海默病痴呆。我们在 Rush 记忆和衰老项目的 1068 名参与者中检查了阿尔茨海默病（AD）进展过程中运动活动波动的分形标度行为的纵向变化。每年最多记录长达 10 天的运动活动，时间长达 13 年。在同一参与者中每年进行认知评估和临床诊断。我们发现，分形调节随着时间的推移逐渐恶化（p<0.0001），即使在没有认知障碍的阶段也是如此。在轻度认知障碍的诊断后，退化速度增加了一倍以上，在阿尔茨海默病痴呆的诊断后进一步增加了一倍以上（p≤0.0005）。此外，分形调节的纵向退化与认知表现的下降在无认知障碍到轻度认知障碍再到 AD 的整个进展过程中显著相关（p<0.001）。在包括仅 255 名尸检证实为阿尔茨海默病病理学的死亡者的后续敏感性分析中，所有影响仍然相同。这些结果表明，AD 的进展加速了分形的退化，分形的退化可能是 AD 过程的一个组成部分。
