背景:关于神经精神症状和血浆生物标志物在整个阿尔茨海默氏症连续体之间的关联知之甚少。
方法:共有305名淀粉样蛋白-β(Aβ)沉积的个体(通过18F-florbetapirPET测定)参与了这项研究,包括认知正常对照(n=53),主观认知能力下降(SCD,n=75),轻度认知障碍(MCI,n=74),和痴呆(n=103)。血浆生物标志物(Aβ1-42,Aβ1-40,总tau[t-tau],磷酸化tau181[p-tau181],和神经丝光[NfL]),完成载脂蛋白E(APOE)基因分型和神经精神调查问卷(NPI-Q)。神经精神症状分为四个亚症状(多动症,精神病,情感,和冷漠)。进行Logistic回归分析以研究神经精神症状与血浆生物标志物之间的关系。
结果:约三分之一的认知未受损个体(正常对照组:34.0%,SCD:28.0%)报告了一种或多种神经精神症状,更多的症状阶段,如MCI(40.5%)和痴呆(81.0%)。与SCD和健康对照组相比,痴呆组的血浆NfL显着增加,与异常运动行为的高风险有关,焦虑,睡眠障碍,去抑制,和兴奋。年龄较大(比值比[OR]=1.079,95%置信区间[CI]=1.022-1.140,p=0.006),较低的认知评分(OR=0.846,95CI=0.791-0.905,p<0.001)和血浆NfL升高(OR=1.021,95CI=1.00-1.042,p=0.041)可以预测精神病。在所有组的血浆Aβ1-42/Aβ1-40,t-tau或p-tau181中没有发现显着差异,与神经精神症状无关。
结论:横截面设计,小样本量和使用NPI-Q.
结论:这项研究支持神经精神症状作为临床前阿尔茨海默病的早期表现,并建议血浆NfL是检测阿尔茨海默氏连续体中神经精神症状的潜在生物标志物。
Little is known about association between neuropsychiatric symptoms and plasma biomarkers across the entire Alzheimer\'s continuum.
A total of 305 individuals with amyloid-β (Aβ) deposition (determined by 18F-florbetapir PET) participated in this study, including cognitively normal controls (n = 53), subjective cognitive decline (SCD, n = 75), mild cognitive impairment (MCI, n = 74), and dementia (n = 103). Plasma biomarkers (Aβ1-42, Aβ1-40, total tau [t-tau], phosphorylated tau 181 [p-tau181], and neurofilament light [NfL]), apolipoprotein E (APOE) genotyping and Neuropsychiatric Inventory Questionnaire (NPI-Q) were completed. Neuropsychiatric symptoms were classified into four subsymdromes (hyperactivity, psychosis, affective, and apathy). Logistic regression analysis was conducted to investigate relationships between neuropsychiatric symptoms and plasma biomarkers.
About one-third of cognitively unimpaired individuals (normal controls: 34.0 %, SCD: 28.0 %) reported one or more neuropsychiatric symptoms, and more in symptomatic stages such as MCI (40.5 %) and dementia (81.0 %). Plasma NfL significantly increased in dementia group compared to SCD and healthy controls, relating to a higher risk of aberrant motor behavior, anxiety, sleep disturbance, disinhibition, and euphoria. Older age (odds ratio [OR] = 1.079, 95 % confidence interval [CI] = 1.022-1.140, p = 0.006), lower cognitive score (OR = 0.846, 95%CI = 0.791-0.905, p < 0.001) and increased plasma NfL (OR = 1.021, 95%CI = 1.00-1.042, p = 0.041) could predict psychosis. No significant differences were found in plasma Aβ1-42/Aβ1-40, t-tau or p-tau181 across all groups, and none correlated with neuropsychiatric symptoms.
The cross-sectional design, small sample size and use of NPI-Q.
This study supported neuropsychiatric symptoms as early manifestations of preclinical Alzheimer\'s disease, and suggested plasma NfL to be a potential biomarker for detecting neuropsychiatric symptoms in Alzheimer\'s continuum.