Risacher Shannon L, WuDunn Darrell, Tallman Eileen F, West John D, Gao Sujuan, Farlow Martin R, Brosch Jared R, Apostolova Liana G, Saykin Andrew J
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Brain Commun. 2020;2(1):fcaa019. doi: 10.1093/braincomms/fcaa019. Epub 2020 Feb 26.
Visual deficits are common in neurodegenerative diseases including Alzheimer's disease. We sought to determine the association between visual contrast sensitivity and neuroimaging measures of Alzheimer's disease-related pathophysiology, including cerebral amyloid and tau deposition and neurodegeneration. A total of 74 participants (7 Alzheimer's disease, 16 mild cognitive impairment, 20 subjective cognitive decline, 31 cognitively normal older adults) underwent the frequency doubling technology 24-2 examination, a structural MRI scan and amyloid PET imaging for the assessment of visual contrast sensitivity. Of these participants, 46 participants (2 Alzheimer's disease, 9 mild cognitive impairment, 12 subjective cognitive decline, 23 cognitively normal older adults) also underwent tau PET imaging with [F]flortaucipir. The relationships between visual contrast sensitivity and cerebral amyloid and tau, as well as neurodegeneration, were assessed using partial Pearson correlations, covaried for age, sex and race and ethnicity. Voxel-wise associations were also evaluated for amyloid and tau. The ability of visual contrast sensitivity to predict amyloid and tau positivity were assessed using forward conditional logistic regression and receiver operating curve analysis. All analyses first were done in the full sample and then in the non-demented at-risk individuals (subjective cognitive decline and mild cognitive impairment) only. Significant associations between visual contrast sensitivity and regional amyloid and tau deposition were observed across the full sample and within subjective cognitive decline and mild cognitive impairment only. Voxel-wise analysis demonstrated strong associations of visual contrast sensitivity with amyloid and tau, primarily in temporal, parietal and occipital brain regions. Finally, visual contrast sensitivity accurately predicted amyloid and tau positivity. Alterations in visual contrast sensitivity were related to cerebral deposition of amyloid and tau, suggesting that this measure may be a good biomarker for detecting Alzheimer's disease-related pathophysiology. Future studies in larger patient samples are needed, but these findings support the power of these measures of visual contrast sensitivity as a potential novel, inexpensive and easy-to-administer biomarker for Alzheimer's disease-related pathology in older adults at risk for cognitive decline.
视觉缺陷在包括阿尔茨海默病在内的神经退行性疾病中很常见。我们试图确定视觉对比敏感度与阿尔茨海默病相关病理生理学的神经影像学指标之间的关联，这些指标包括脑淀粉样蛋白和tau蛋白沉积以及神经退行性变。共有74名参与者（7名阿尔茨海默病患者、16名轻度认知障碍患者、20名主观认知下降者、31名认知正常的老年人）接受了倍频技术24-2检查、结构磁共振成像扫描和淀粉样蛋白PET成像，以评估视觉对比敏感度。在这些参与者中，46名参与者（2名阿尔茨海默病患者、9名轻度认知障碍患者、12名主观认知下降者、23名认知正常的老年人）还接受了用[F]氟代tau蛋白进行的tau蛋白PET成像。使用偏Pearson相关性评估视觉对比敏感度与脑淀粉样蛋白和tau蛋白以及神经退行性变之间的关系，并对年龄、性别、种族和民族进行协变量调整。还评估了淀粉样蛋白和tau蛋白的体素水平关联。使用前向条件逻辑回归和受试者工作特征曲线分析评估视觉对比敏感度预测淀粉样蛋白和tau蛋白阳性的能力。所有分析首先在全样本中进行，然后仅在非痴呆高危个体（主观认知下降和轻度认知障碍）中进行。在全样本以及仅在主观认知下降和轻度认知障碍组中，观察到视觉对比敏感度与区域淀粉样蛋白和tau蛋白沉积之间存在显著关联。体素水平分析表明，视觉对比敏感度与淀粉样蛋白和tau蛋白存在强关联，主要位于颞叶、顶叶和枕叶脑区。最后，视觉对比敏感度准确预测了淀粉样蛋白和tau蛋白阳性。视觉对比敏感度的改变与淀粉样蛋白和tau蛋白的脑内沉积有关，这表明该指标可能是检测阿尔茨海默病相关病理生理学的良好生物标志物。需要在更大的患者样本中进行进一步研究，但这些发现支持了这些视觉对比敏感度测量方法作为一种潜在的新型、廉价且易于实施的生物标志物，用于检测有认知下降风险的老年人中与阿尔茨海默病相关的病理情况的作用。
