Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington, KY, USA.
Alzheimer's Disease Center, Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, KY, USA.
J Alzheimers Dis. 2021;79(2):531-541. doi: 10.3233/JAD-200931.
Early prognosis of high-risk older adults for amnestic mild cognitive impairment (aMCI), using noninvasive and sensitive neuromarkers, is key for early prevention of Alzheimer's disease. We have developed individualized measures in electrophysiological brain signals during working memory that distinguish patients with aMCI from age-matched cognitively intact older individuals.
Here we test longitudinally the prognosis of the baseline neuromarkers for aMCI risk. We hypothesized that the older individuals diagnosed with incident aMCI already have aMCI-like brain signatures years before diagnosis.
Electroencephalogram (EEG) and memory performance were recorded during a working memory task at baseline. The individualized baseline neuromarkers, annual cognitive status, and longitudinal changes in memory recall scores up to 10 years were analyzed.
Seven of the 19 cognitively normal older adults were diagnosed with incident aMCI for a median 5.2 years later. The seven converters' frontal brainwaves were statistically identical to those patients with diagnosed aMCI (n = 14) at baseline. Importantly, the converters' baseline memory-related brainwaves (reduced mean frontal responses to memory targets) were significantly different from those who remained normal. Furthermore, differentiation pattern of left frontal memory-related responses (targets versus nontargets) was associated with an increased risk hazard of aMCI (HR = 1.47, 95% CI 1.03, 2.08).
The memory-related neuromarkers detect MCI-like brain signatures about five years before diagnosis. The individualized frontal neuromarkers index increased MCI risk at baseline. These noninvasive neuromarkers during our Bluegrass memory task have great potential to be used repeatedly for individualized prognosis of MCI risk and progression before clinical diagnosis.
使用非侵入性和敏感的神经标志物对有遗忘型轻度认知障碍（aMCI）风险的高危老年人进行早期预后，是预防阿尔茨海默病的关键。我们已经开发出了在工作记忆期间脑电信号中的个体化测量方法，可以将 aMCI 患者与年龄匹配的认知正常老年人区分开来。
本文通过纵向测试基线神经标志物对 aMCI 风险的预后。我们假设，在诊断为新发 aMCI 的老年人中，早在几年前就已经存在类似 aMCI 的大脑特征。
在基线时进行工作记忆任务期间记录脑电图（EEG）和记忆表现。分析了个体化的基线神经标志物、每年的认知状态以及长达 10 年的记忆回忆评分的纵向变化。
在 19 名认知正常的老年人中，有 7 人在中位 5.2 年后被诊断为新发 aMCI。这 7 名转化者的额部脑电波与基线时被诊断为 aMCI 的患者（n=14）的脑电波在统计学上完全相同。重要的是，转化者的基线与记忆相关的脑电波（对记忆目标的额部反应减少）与那些保持正常的人有显著差异。此外，左额部记忆相关反应（目标与非目标）的分化模式与 aMCI 的风险增加相关（HR=1.47，95%CI 1.03，2.08）。
记忆相关的神经标志物在诊断前大约五年就可以检测到 MCI 样的大脑特征。基线时的个体化额部神经标志物指标预示着 MCI 风险增加。在我们的“Bluegrass 记忆任务”中，这些非侵入性的神经标志物具有很大的潜力，可在临床诊断前用于重复预测 MCI 风险和进展的个体化预后。
