OBJECTIVE To understand the role of depressive symptoms in preclinical Alzheimer's disease, it is essential to define their temporal relationship to Alzheimer's proteinopathies in cognitively normal older adults. The study objective was to examine associations of brain amyloid beta and longitudinal measures of depression and depressive symptom clusters in a cognitively normal sample of older adults. METHOD A total of 270 community-dwelling, cognitively normal elderly individuals underwent baseline Pittsburgh compound B (PiB) positron emission tomography (PET) measures of cortical aggregate amyloid beta and annual assessments with the 30-item Geriatric Depression Scale (GDS). The authors evaluated continuous PiB binding as a predictor of GDS score or GDS cluster, calculated as total scores and mean scores for three GDS item clusters (apathy-anhedonia, dysphoria, and anxiety-concentration), across time (1-5 years; mean=3.8 years) in separate mixed-effects models with backward elimination. Initial predictors included PiB binding, age, sex, Hollingshead score, American National Adult Reading Test (AMNART) score, apolipoprotein E ε4 status, depression history, and their interactions with time. RESULTS Higher PiB binding predicted accelerated rates of increase in GDS score over time, adjusting for depression history. Higher PiB binding also predicted steeper rates of increase for anxiety-concentration scores, adjusting for depression history and the AMNART score-by-time interaction. In a post hoc model estimating anxiety scores without concentration disturbance items, the PiB binding-by-time interaction remained significant. CONCLUSIONS Higher amyloid beta burden was associated with increasing anxious-depressive symptoms over time in cognitively normal older individuals. Prior depression history was related to higher but not worsening symptom ratings. These results suggest a direct or indirect association of elevated amyloid beta levels with worsening anxious-depressive symptoms and support the hypothesis that emerging neuropsychiatric symptoms represent an early manifestation of preclinical Alzheimer's disease.

中文翻译：

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认知正常的成年人中淀粉样蛋白β和焦虑抑郁症状的纵向关联。

目的为了了解抑郁症状在临床前阿尔茨海默氏病中的作用，有必要确定认知正常的成年人中抑郁症状与阿尔茨海默氏蛋白病的时间关系。该研究的目的是检查认知正常的成年人中大脑淀粉样蛋白β与抑郁和抑郁症状群的纵向测量之间的关系。方法共有270名居住在社区，认知正常的老年人进行了匹兹堡化合物B（PiB）正电子发射断层扫描（PET）皮质骨淀粉样β的基线测量，并使用30项老年抑郁量表（GDS）进行了年度评估。作者评估了连续的PiB结合可预测GDS得分或GDS簇，计算方法为三个GDS项目群（麻木性快感，烦躁不安和焦虑症浓度）在整个时间（1-5年；平均= 3.8年）中的总分和平均分，该模型具有向后消除的独立混合效应模型。最初的预测因素包括PiB结合，年龄，性别，Hollingshead得分，美国国家成人阅读测试（AMNART）得分，载脂蛋白Eε4状态，抑郁史及其与时间的相互作用。结果较高的PiB结合度可预测GDS分数随时间的增加加速速率，并根据抑郁史进行调整。较高的PiB结合度还预测了焦虑集中度评分的上升速度会较快，并根据抑郁史和AMNART逐时交互作用进行了调整。在一个事后模型中，评估没有分数干扰项目的焦虑评分时，PiB的按时间绑定交互仍然很重要。结论认知正常的老年人随着时间的推移，淀粉样蛋白β负荷增加与焦虑抑郁症状的增加相关。先前的抑郁史与较高但不恶化的症状等级有关。这些结果表明，淀粉样蛋白β水平升高与焦虑抑郁症状的恶化直接或间接相关，并支持新出现的神经精神症状代表临床前阿尔茨海默氏病的早期表现的假说。