Stevens Daniel A, Workman Clifford I, Kuwabara Hiroto, Butters Meryl A, Savonenko Alena, Nassery Najilla, Gould Neda, Kraut Michael, Joo Jin Hui, Kilgore Jessica, Kamath Vidya, Holt Daniel P, Dannals Robert F, Nandi Ayon, Onyike Chiadi U, Smith Gwenn S
Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Division of Nuclear Medicine and Molecular Imaging, Russell H. Morgan Department of Radiology and Radiological Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Brain Commun. 2022 Feb 7;4(1):fcac016. doi: 10.1093/braincomms/fcac016. eCollection 2022.
Beta-amyloid deposition is one of the earliest pathological markers associated with Alzheimer's disease. Mild cognitive impairment in the setting of beta-amyloid deposition is considered to represent a preclinical manifestation of Alzheimer's disease. imaging studies are unique in their potential to advance our understanding of the role of beta-amyloid deposition in cognitive deficits in Alzheimer's disease and in mild cognitive impairment. Previous work has shown an association between global cortical measures of beta-amyloid deposition ('amyloid positivity') in mild cognitive impairment with greater cognitive deficits and greater risk of progression to Alzheimer's disease. The focus of the present study was to examine the relationship between the regional distribution of beta-amyloid deposition and specific cognitive deficits in people with mild cognitive impairment and cognitively normal elderly individuals. Forty-seven participants with multi-domain, amnestic mild cognitive impairment (43% female, aged 57-82 years) and 37 healthy, cognitively normal comparison subjects (42% female, aged 55-82 years) underwent clinical and neuropsychological assessments and high-resolution positron emission tomography with the radiotracer C-labelled Pittsburgh compound B to measure beta-amyloid deposition. Brain-behaviour partial least-squares analysis was conducted to identify spatial patterns of beta-amyloid deposition that correlated with the performance on neuropsychological assessments. Partial least-squares analysis identified a single significant ( < 0.001) latent variable which accounted for 80% of the covariance between demographic and cognitive measures and beta-amyloid deposition. Performance in immediate verbal recall ( = -0.46 ± 0.07, < 0.001), delayed verbal recall ( = -0.39 ± 0.09, < 0.001), immediate visual-spatial recall ( = -0.39 ± 0.08, < 0.001), delayed visual-spatial recall ( = -0.45 ± 0.08, < 0.001) and semantic fluency ( = -0.33 ± 0.11, = 0.002) but not phonemic fluency ( = -0.05 ± 0.12, < 0.705) negatively covaried with beta-amyloid deposition in the identified regions. Partial least-squares analysis of the same cognitive measures with grey matter volumes showed similar associations in overlapping brain regions. These findings suggest that the regional distribution of beta-amyloid deposition and grey matter volumetric decreases is associated with deficits in executive function and memory in mild cognitive impairment. Longitudinal analysis of these relationships may advance our understanding of the role of beta-amyloid deposition in relation to grey matter volumetric decreases in cognitive decline.
β-淀粉样蛋白沉积是与阿尔茨海默病相关的最早病理标志物之一。在β-淀粉样蛋白沉积情况下的轻度认知障碍被认为是阿尔茨海默病的临床前表现。影像学研究在推进我们对β-淀粉样蛋白沉积在阿尔茨海默病和轻度认知障碍认知缺陷中所起作用的理解方面具有独特潜力。先前的研究表明，轻度认知障碍中β-淀粉样蛋白沉积的全脑皮质测量值（“淀粉样蛋白阳性”）与更严重的认知缺陷以及进展为阿尔茨海默病的更高风险之间存在关联。本研究的重点是检查轻度认知障碍患者和认知正常的老年人中β-淀粉样蛋白沉积的区域分布与特定认知缺陷之间的关系。47名患有多领域遗忘型轻度认知障碍的参与者（43%为女性，年龄57 - 82岁）和37名健康的、认知正常的对照受试者（42%为女性，年龄55 - 82岁）接受了临床和神经心理学评估，并使用放射性示踪剂C标记的匹兹堡化合物B进行高分辨率正电子发射断层扫描以测量β-淀粉样蛋白沉积。进行了脑-行为偏最小二乘分析，以确定与神经心理学评估表现相关的β-淀粉样蛋白沉积的空间模式。偏最小二乘分析确定了一个单一的显著（<0.001）潜在变量，该变量解释了人口统计学和认知测量与β-淀粉样蛋白沉积之间80%的协方差。即时言语回忆（= -0.46±0.07，<0.001）、延迟言语回忆（= -0.39±0.09，<0.001）、即时视觉空间回忆（= -0.39±0.08，<0.001）、延迟视觉空间回忆（= -0.45±0.08，<0.001）和语义流畅性（= -0.33±0.11，= 0.002）但非音素流畅性（= -0.05±0.12，<0.7
