Research Center, Institut universitaire de gériatrie de Montréal, Montreal, Canada; Department of Psychology, Université de Montréal, Montreal, Canada.
Department of Psychiatry, McGill University, Montreal, Canada; Douglas Research Centre, Montreal, Canada.
Neuroimage Clin. 2021;30:102643. doi: 10.1016/j.nicl.2021.102643. Epub 2021 Mar 26.
The goal of this study was to assess how task-related hyperactivation relates to brain network dysfunction and memory performance in individuals at risk of Alzheimer's disease (AD). Eighty participants from the CIMA-Q cohort were included, of which 28 had subjective cognitive decline plus (SCD), as they had memory complaints and worries in addition to a smaller hippocampal volume and/or an APOE4 allele, 26 had amnestic mild cognitive impairment (MCI) and 26 were healthy controls without memory complaints. Functional magnetic resonance imaging (fMRI) activation was measured during an object-location memory task. Seed-partial least square analyses (seed-PLS) were conducted in controls and in the SCD/MCI groups to yield sets of orthogonal latent variables (LVs) assessing the triple association between: i) seed activity in brain regions found to be hyperactive in individuals at risk of AD (left hippocampus, left superior parietal lobule, right inferior temporal lobe), ii) latent patterns of whole-brain task-related activation, and iii) associative memory performance. Three LVs in the SCD and MCI groups (67.88% of total covariance explained) and two LVs in the controls (77.85% of total covariance explained) were significant. While controls and SCD/MCI groups shared a common pattern of memory-related connectivity, patterns of hyperactivation-networks interactions were unique to the clinical groups. Interestingly, higher hippocampal connectivity was associated with poorer memory performance whereas higher neocortical connectivity predicted better memory performance in SCD and MCI groups. Our data provides empirical evidence that early dysfunction in brain activation and connectivity is present in the very early stages of AD and offers new insights on the relationship between functional brain alterations and memory performance.
本研究旨在评估任务相关过度激活与阿尔茨海默病（AD）风险个体的脑网络功能障碍和记忆表现之间的关系。该研究纳入了 CIMA-Q 队列的 80 名参与者，其中 28 名参与者有主观认知下降（SCD），因为他们除了海马体体积较小和/或 APOE4 等位基因外，还有记忆主诉和担忧；26 名参与者有遗忘型轻度认知障碍（MCI）；26 名参与者为无记忆主诉的健康对照者。在物体位置记忆任务中测量功能磁共振成像（fMRI）激活。在对照组和 SCD/MCI 组中进行种子部分最小二乘分析（seed-PLS），以产生一组正交潜在变量（LV），评估以下三重关联：i）在 AD 风险个体中发现的过度活跃脑区（左侧海马体、左侧顶叶上回、右侧颞下回）的种子活动；ii）全脑任务相关激活的潜在模式；iii）联想记忆表现。SCD 和 MCI 组中有三个 LV（总协方差的 67.88%解释）和对照组中有两个 LV（总协方差的 77.85%解释）具有统计学意义。虽然对照组和 SCD/MCI 组共享与记忆相关的连接的共同模式，但过度激活-网络相互作用的模式是临床组特有的。有趣的是，海马体连接性越高，记忆表现越差，而新皮质连接性越高，SCD 和 MCI 组的记忆表现越好。我们的数据提供了经验证据，表明 AD 早期阶段存在脑激活和连接的早期功能障碍，并提供了关于功能脑改变与记忆表现之间关系的新见解。
