PDF(Pubmed)
Abstract：
BACKGROUND: Stronger resting-state functional connectivity of the default mode and frontoparietal control networks has been associated with cognitive resilience to Alzheimer\'s disease related pathology and neurodegeneration in smaller cohort studies.
OBJECTIVE: We investigated whether these networks are associated with longitudinal CR to AD biomarkers of beta-amyloid (Aβ).
METHODS: Longitudinal mixed.
METHODS: The Anti-Amyloid Treatment in Asymptomatic Alzheimer\'s Disease (A4) study and its natural history observation arm, the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study.
METHODS: A sample of 1,021 cognitively unimpaired older adults (mean age = 71.2 years [SD = 4.7 years], 61% women, 42% APOEε4 carriers, 52% Aβ positive).
METHODS: Global cognitive performance (Preclinical Alzheimer\'s Cognitive Composite) was assessed over an average 5.4 year follow-up period (SD = 2 years). Cortical Aβ and functional connectivity (left and right frontoparietal control and default mode networks) were estimated from fMRI and PET, respectively, at baseline. Covariates included baseline age, APOEε4 carrier status, years of education, adjusted gray matter volume, head motion, study group, cumulative treatment exposure, and cognitive test version.
RESULTS: Mixed effects models revealed that functional connectivity of the left frontoparietal control network moderated the negative effect of Aβ on cognitive change (p = .025) such that stronger connectivity was associated with reduced Aβ-related cognitive decline.
CONCLUSIONS: Our results demonstrate a potential protective effect of functional connectivity in preclinical AD, such that stronger connectivity in this network is associated with slower Aβ-related cognitive decline.
OBJECTIVE: We investigated whether these networks are associated with longitudinal CR to AD biomarkers of beta-amyloid (Aβ).
METHODS: Longitudinal mixed.
METHODS: The Anti-Amyloid Treatment in Asymptomatic Alzheimer\'s Disease (A4) study and its natural history observation arm, the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study.
METHODS: A sample of 1,021 cognitively unimpaired older adults (mean age = 71.2 years [SD = 4.7 years], 61% women, 42% APOEε4 carriers, 52% Aβ positive).
METHODS: Global cognitive performance (Preclinical Alzheimer\'s Cognitive Composite) was assessed over an average 5.4 year follow-up period (SD = 2 years). Cortical Aβ and functional connectivity (left and right frontoparietal control and default mode networks) were estimated from fMRI and PET, respectively, at baseline. Covariates included baseline age, APOEε4 carrier status, years of education, adjusted gray matter volume, head motion, study group, cumulative treatment exposure, and cognitive test version.
RESULTS: Mixed effects models revealed that functional connectivity of the left frontoparietal control network moderated the negative effect of Aβ on cognitive change (p = .025) such that stronger connectivity was associated with reduced Aβ-related cognitive decline.
CONCLUSIONS: Our results demonstrate a potential protective effect of functional connectivity in preclinical AD, such that stronger connectivity in this network is associated with slower Aβ-related cognitive decline.
摘要：
背景：在较小的队列研究中，默认模式和额叶控制网络的更强静息状态功能连接与阿尔茨海默病相关病理和神经变性的认知弹性相关。
目的：我们研究了这些网络是否与β-淀粉样蛋白（Aβ）的AD生物标志物的纵向CR相关。
方法：纵向混合。
方法：无症状阿尔茨海默病（A4）的抗淀粉样蛋白治疗研究及其自然史观察臂，淀粉样蛋白风险和神经变性的纵向评估（LEARN）研究。
方法：1,021名认知未受损的老年人的样本（平均年龄=71.2岁[SD=4.7岁]，61%的女性，42%APOEε4携带者，52%Aβ阳性)。
方法：在平均5.4年的随访期（SD=2年）内评估总体认知表现（临床前阿尔茨海默病认知综合）。根据功能磁共振成像和PET估计皮质Aβ和功能连通性（左和右额顶控制和默认模式网络），分别,在基线。协变量包括基线年龄，APOEε4载波状态，多年的教育，调整后的灰质体积，头部运动,研究组,累积治疗暴露，和认知测试版本。
结果：混合效应模型显示，左额顶控制网络的功能连接调节了Aβ对认知变化的负面影响（p=0.025），因此更强的连接与Aβ相关的认知下降减少有关。
结论：我们的结果证明了功能性连接在临床前AD中的潜在保护作用，因此，该网络中更强的连通性与较慢的Aβ相关认知衰退有关。
目的：我们研究了这些网络是否与β-淀粉样蛋白（Aβ）的AD生物标志物的纵向CR相关。
方法：纵向混合。
方法：无症状阿尔茨海默病（A4）的抗淀粉样蛋白治疗研究及其自然史观察臂，淀粉样蛋白风险和神经变性的纵向评估（LEARN）研究。
方法：1,021名认知未受损的老年人的样本（平均年龄=71.2岁[SD=4.7岁]，61%的女性，42%APOEε4携带者，52%Aβ阳性)。
方法：在平均5.4年的随访期（SD=2年）内评估总体认知表现（临床前阿尔茨海默病认知综合）。根据功能磁共振成像和PET估计皮质Aβ和功能连通性（左和右额顶控制和默认模式网络），分别,在基线。协变量包括基线年龄，APOEε4载波状态，多年的教育，调整后的灰质体积，头部运动,研究组,累积治疗暴露，和认知测试版本。
结果：混合效应模型显示，左额顶控制网络的功能连接调节了Aβ对认知变化的负面影响（p=0.025），因此更强的连接与Aβ相关的认知下降减少有关。
结论：我们的结果证明了功能性连接在临床前AD中的潜在保护作用，因此，该网络中更强的连通性与较慢的Aβ相关认知衰退有关。
