Donovan Nancy J, Wadsworth Lauren P, Lorius Natacha, Locascio Joseph J, Rentz Dorene M, Johnson Keith A, Sperling Reisa A, Marshall Gad A
Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Am J Geriatr Psychiatry. 2014 Nov;22(11):1168-79. doi: 10.1016/j.jagp.2013.03.006. Epub 2013 Jul 24.
To examine regions of cortical thinning and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers associated with apathy and hallucinations in a continuum of individuals including clinically normal elderly, mild cognitive impairment, and mild AD dementia.
Cross-sectional and longitudinal studies.
Fifty-seven research sites across North America.
Eight-hundred twelve community-dwelling volunteers; 413 participants in the CSF sub-study.
Structural magnetic resonance imaging data and CSF concentrations of amyloid-β 1-42, total tau, and phosphorylated tau derived from the Alzheimer Disease Neuroimaging Initiative database were analyzed. Apathy and hallucinations were measured at baseline and over 3 years using the Neuropsychiatric Inventory-Questionnaire. General linear models and mixed effects models were used to evaluate the relationships among baseline cortical thickness in seven regions, and baseline CSF biomarkers, apathy, and hallucinations at baseline and longitudinally. Covariates included diagnosis, sex, age, apolipoprotein E genotype, premorbid intelligence, memory performance, processing speed, antidepressant use, and AD duration.
Reduced baseline inferior temporal cortical thickness was predictive of increasing apathy over time, and reduced supramarginal cortical thickness was predictive of increasing hallucinations over time. There was no association with cortical thickness at baseline. CSF biomarkers were not related to severity of apathy or hallucinations in cross-sectional or longitudinal analyses.
These results suggest that greater baseline temporal and parietal atrophy is associated with worsening apathy and hallucinations in a large AD spectrum cohort, while adjusting for multiple disease-related variables. Localized cortical neurodegeneration may contribute to the pathophysiology of apathy and hallucinations and their adverse consequences in AD.
在包括临床正常老年人、轻度认知障碍和轻度阿尔茨海默病痴呆患者的连续个体中，研究与冷漠和幻觉相关的皮质变薄区域及脑脊液（CSF）阿尔茨海默病（AD）生物标志物。
横断面研究和纵向研究。
北美57个研究地点。
812名社区居住志愿者；413名参与CSF子研究。
分析来自阿尔茨海默病神经影像倡议数据库的结构磁共振成像数据以及脑脊液中淀粉样β蛋白1-42、总tau蛋白和磷酸化tau蛋白的浓度。使用神经精神科问卷在基线和3年期间测量冷漠和幻觉。采用一般线性模型和混合效应模型评估7个区域的基线皮质厚度、基线脑脊液生物标志物、基线时及纵向的冷漠和幻觉之间的关系。协变量包括诊断、性别、年龄、载脂蛋白E基因型、病前智力、记忆表现、处理速度、抗抑郁药使用情况和AD病程。
基线时颞下回皮质厚度降低可预测随时间推移冷漠症状加重，缘上回皮质厚度降低可预测随时间推移幻觉症状加重。与基线时的皮质厚度无关联。在横断面或纵向分析中，脑脊液生物标志物与冷漠或幻觉的严重程度无关。
这些结果表明，在一个大型AD谱系队列中，在调整多个疾病相关变量后，更大程度的基线颞叶和顶叶萎缩与冷漠和幻觉的恶化相关。局部皮质神经变性可能导致AD中冷漠和幻觉的病理生理学及其不良后果。
