Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden; Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden; Memory Clinic, Skåne University Hospital, Lund, Sweden.
Neurobiol Aging. 2018 Apr;64:76-84. doi: 10.1016/j.neurobiolaging.2017.12.018. Epub 2017 Dec 27.
The objective of this study was to determine the cognitive and functional decline and development of brain injury in individuals progressing from preclinical (β-amyloid positive cognitively normal) to prodromal Alzheimer's disease (AD) (β-amyloid positive mild cognitive impairment [MCI]), and compare this with individuals who progress to MCI in the absence of significant amyloid pathology. Seventy-five cognitively healthy participants who progressed to MCI were followed for 4 years on average and up to 10 years. We tested effects of β-amyloid (Aβ) on measures of cognition, functional status, depressive symptoms, and brain structure and metabolism. Preclinical AD subjects showed greater cognitive decline in multiple domains and increased cerebrospinal fluid phosphorylated tau levels at baseline while Aβ-negative progressors showed increased rates of white matter hyperintensity accumulation and had a greater frequency of depressive symptoms at baseline. Aβ status did not influence patterns of brain atrophy, but preclinical AD subjects showed greater decline of brain metabolism than Aβ-negative progressors. Several unique features separate the transition from preclinical to prodromal AD from other causes of cognitive decline. These features may facilitate early diagnosis and treatment of AD, especially in clinical trials aimed at halting the progression from preclinical to prodromal AD.
本研究旨在确定从临床前期（β-淀粉样蛋白阳性认知正常）到前驱期阿尔茨海默病（AD）（β-淀粉样蛋白阳性轻度认知障碍 [MCI]）的个体认知和功能下降以及脑损伤的发展，并将其与无明显淀粉样蛋白病理进展为 MCI 的个体进行比较。75 名认知健康的参与者在平均 4 年的时间内进展为 MCI，最长可达 10 年。我们测试了β-淀粉样蛋白（Aβ）对认知、功能状态、抑郁症状以及大脑结构和代谢的影响。在基线时，临床前期 AD 受试者在多个领域的认知下降更为明显，脑脊液磷酸化 tau 水平升高，而 Aβ 阴性进展者的脑白质高信号积累速度更快，基线时抑郁症状的频率更高。Aβ 状态并不影响脑萎缩模式，但临床前期 AD 受试者的脑代谢下降幅度大于 Aβ 阴性进展者。一些独特的特征将从临床前期到前驱期 AD 的转变与其他认知下降的原因区分开来。这些特征可能有助于 AD 的早期诊断和治疗，尤其是在旨在阻止从临床前期到前驱期 AD 进展的临床试验中。
