A longitudinal study of the task‐related activation trajectory in people with mild cognitive impairment and subjective cognitive decline

Abstract

AbstractBackgroundBrain hyperactivation — defined as higher level of activation compared to controls — was suggested as a very early signature of prodromal Alzheimer’s disease (AD), which would gradually decrease with progression to dementia. Longitudinal studies with people who have mild cognitive impairment (MCI) and subjective cognitive decline (SCD) can be used to capture the temporal dynamics and inter‐individual differences of these very early activation changes. Here, we aimed to identify the temporal trajectory of task‐related activation in participants with SCD and MCI from the CIMA‐Q cohort, which has data collected at multiple time‐points. We thus identified subgroups based on their common activation trajectory and characterized subgroups defined from the activation trajectory.MethodThe study included 53 older participants (40 SCD; 13 MCI) from the CIMA‐Q cohort with neuroimaging data collected over at least two time‐points (66‐85 years old; 36 women, 17 men). An fMRI examination was done every two years (2‐4 time‐points; average follow‐up: 3.2 years). Task‐related activation was measured during an associative memory encoding task. Group‐based trajectory models were estimated to identify homogeneous groups of participants based on activation trajectories in the hippocampus and in regions from the cortical signature of AD. Groups defined based on activation trajectories were then compared using Apolipoprotein‐ε4 (ApoE4), baseline cognition and hippocampal volume.ResultTwo different trajectories of activation were identified: Trajectory 1 was found in several cortical regions and was characterized by a high level of initial activation, which decreased over time. Trajectory 2 was characterized by a lower activation level, which remained stable over time or increased slightly on time‐point 4. Smaller hippocampal volume and ApoE4 were associated with Trajectory 1 for the left angular gyrus, and left hippocampal and right middle temporal gyrus activation, respectively.ConclusionAn inverted U‐shape trajectory was found with high activation followed by gradually decreasing activation in AD‐signature regions. This trajectory was associated with smaller hippocampal volume and/or the presence of ApoE4 allele, both of which are biomarkers that increase the likelihood of developing AD. This finding supports the hypothesis that the inverted U‐shape trajectory of hyperactivation could be an index of prodromal AD.