Language dysfunction is common in Alzheimer’s disease. There is increasing interest in the preclinical or asymptomatic phase of Alzheimer’s disease. Here we examined in 35 cognitively intact older adults (age range 52–78 years at baseline, 17 male) in a longitudinal study design the association between accumulation of amyloid over a 5–6-year period, measured using PET, and functional changes in the language network measured over the same time period using task-related functional MRI. In the same participants, we also determined the association between the longitudinal functional MRI changes and a cross-sectional measure of tau load as measured with 18F-AV1451 PET. As predicted, the principal change occurred in posterior temporal cortex. In the cortex surrounding the right superior temporal sulcus, the response amplitude during the associative-semantic versus visuo-perceptual task increased over time as amyloid load accumulated (Pcorrected = 0.008). In a whole-brain voxel-wise analysis, amyloid accumulation was also associated with a decrease in response amplitude in the left inferior frontal sulcus (Pcorrected = 0.009) and the right dorsomedial prefrontal cortex (Pcorrected = 0.005). In cognitively intact older adults, cross-sectional tau load was not associated with longitudinal changes in functional MRI response amplitude. Our findings confirm the central role of the neocortex surrounding the posterior superior temporal sulcus as the area of predilection within the language network in the earliest stages of Alzheimer’s disease. Amyloid accumulation has an impact on cognitive brain circuitry in the asymptomatic phase of Alzheimer’s disease.

中文翻译：

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β淀粉样蛋白积累时语言系统的变化

语言功能障碍在阿尔茨海默病中很常见。人们对阿尔茨海默病的临床前或无症状阶段越来越感兴趣。在这里，我们在一项纵向研究设计中检查了 35 名认知完整的老年人（基线年龄范围为 52-78 岁，17 名男性）在 5-6 年期间淀粉样蛋白的积累（使用 PET 测量）与功能变化之间的关联。使用任务相关的功能 MRI 在同一时间段内测量语言网络。在相同的参与者中，我们还确定了纵向功能性 MRI 变化与 18F-AV1451 PET 测量的 tau 负载的横截面测量之间的关联。正如预测的那样，主要变化发生在后颞叶皮层。在右颞上沟周围的皮层，随着淀粉样蛋白负荷的积累，联想语义与视觉感知任务期间的响应幅度随着时间的推移而增加（P校正 = 0.008）。在全脑体素分析中，淀粉样蛋白的积累也与左侧额下沟 (Pcorrected = 0.009) 和右侧背内侧前额叶皮层 (Pcorrected = 0.005) 的响应幅度降低有关。在认知完整的老年人中，横截面 tau 负荷与功能性 MRI 反应幅度的纵向变化无关。我们的研究结果证实了围绕后上颞沟的新皮质作为阿尔茨海默病早期阶段语言网络中的偏好区域的核心作用。