Gonzales Mitzi M, Insel Philip S, Nelson Craig, Tosun Duygu, Schöll Michael, Mattsson Niklas, Sacuiu Simona, Bickford David, Weiner Michael W, Mackin R Scott
Department of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Center for Imaging of Neurodegenerative Diseases, Veterans Administration Medical Center, San Francisco, CA, USA.
Int J Geriatr Psychiatry. 2018 Oct;33(10):1305-1311. doi: 10.1002/gps.4926. Epub 2018 Jun 28.
To investigate the association between chronic subsyndromal symptoms of depression (SSD), cerebrospinal fluid (CSF) biomarkers, and neuropsychological performance in individuals with mild cognitive impairment (MCI).
Participants included 238 older adults diagnosed with MCI from the Alzheimer's Disease Neuroimaging Initiative repository with cognitive and CSF amyloid beta (Aβ ), total tau (t-tau), and phosphorylated tau (p-tau) data. The Neuropsychiatric Inventory identified individuals with chronic endorsement (SSD group N = 80) or no endorsement (non-SSD group N = 158) of depressive symptoms across timepoints. CSF biomarker and cognitive performance were evaluated with linear regression models adjusting for age, education, gender, APOE genotype, global cognitive status, and SSD group.
As compared to the non-SSD group, the SSD group displayed lower CSF Aβ levels (β = -24.293, S.E. = 6.345, P < 0.001). No group differences were observed for CSF t-tau (P = 0.497) or p-tau levels (P = 0.392). Lower CSF Aβ levels were associated with poorer performance on learning (β = 0.041, S.E. = 0.018, P = 0.021) and memory (β = -0.012, S.E. = 0.005, P = 0.031) measures, whereas higher CSF t-tau levels were associated with poorer performance on measures of global cognition (β = 0.022, S.E = 0.008, P = 0.007) and language (β = -0.010, S.E = 0.004, P = 0.019). SSD was independently associated with diminished global cognition, learning and memory, language, and executive function performance over and above the effects of CSF biomarkers (all P < 0.05).
MCI participants with SSD displayed diminished CSF Aβ levels but did not differ from non-SSD controls in CSF tau levels. Additionally, CSF biomarkers and SSD independently accounted for variance in cognitive performance, suggesting that these factors may uniquely confer cognitive risk in MCI.
研究轻度认知障碍（MCI）患者的慢性亚综合征性抑郁症状（SSD）、脑脊液（CSF）生物标志物与神经心理学表现之间的关联。
参与者包括来自阿尔茨海默病神经影像学计划数据库的238名被诊断为MCI的老年人，他们有认知和CSF淀粉样蛋白β（Aβ）、总tau蛋白（t-tau）和磷酸化tau蛋白（p-tau）数据。神经精神科问卷确定了在各个时间点有慢性抑郁症状认可（SSD组，N = 80）或无认可（非SSD组，N = 158）的个体。使用线性回归模型评估CSF生物标志物和认知表现，模型对年龄、教育程度、性别、APOE基因型、整体认知状态和SSD组进行了校正。
与非SSD组相比，SSD组的CSF Aβ水平较低（β = -24.293，标准误 = 6.345，P < 0.001）。CSF t-tau（P = 0.497）或p-tau水平未观察到组间差异（P = 0.392）。较低的CSF Aβ水平与学习（β = 0.041，标准误 = 0.018，P = 0.021）和记忆（β = -0.012，标准误 = 0.005，P = 0.031）测量表现较差相关，而较高的CSF t-tau水平与整体认知（β = 0.022，标准误 = 0.008，P = 0.007）和语言（β = -0.010，标准误 = 0.004，P = 0.019）测量表现较差相关。除了CSF生物标志物的影响外，SSD与整体认知、学习和记忆、语言及执行功能表现的降低独立相关（所有P < 0.05）。
患有SSD的MCI参与者CSF Aβ水平降低，但CSF tau水平与非SSD对照组无差异。此外，CSF生物标志物和SSD独立解释了认知表现的差异，表明这些因素可能在MCI中独特地赋予认知风险。
