Correlation between fMRI complexity and cognition in early‐onset Alzheimer’s disease

Abstract

AbstractBackgroundResting state fMRI (rs‐fMRI) studies in Alzheimer’s disease (AD) have shown that the functional connectivity (FC) of resting brain networks is progressively diminished in subjects with mild cognitive impairment (MCI) and AD. However, FC analysis of rs‐fMRI has limited capability to characterize the dynamic fluctuations of rs‐fMRI signals that possess clinically meaningful information. Recently the use of entropy measures as indices of the complexity of rs‐fMRI time‐series that provide alternative and complementary information to current fMRI‐based approaches has been proposed. Unlike FC that relies on the parcellation of nodes or selection of seed regions for network analysis, entropy measures of rs‐fMRI can be calculated on a voxel‐wise basis across the whole brain.MethodHere we investigated the correlation between cognitive performance and rs‐fMRI complexity in a sample of 35 participants (Table1) from the Estudio de Enfermedad de Alzheimer en Jalisciences (EEAJ) project that recruits Latino persons (age 18‐80 yrs) at‐risk for fully‐penetrant ADAD. Imaging data underwent standard preprocessing. Multi‐scale entropy was calculated using Sample Entropy at 6 temporal scales using a pattern matching threshold of m = 2 and sensitivity threshold of r = 0.5. Voxel‐wise partial Spearman‐rank correlation was used to assess the relation between cognitive scores (MoCA, Trails‐B and Reverse Digit Span) including age and gender as covariates.ResultWe found significant positive associations between fMRI complexity and all three cognitive scores across the study cohort. We did not observe any significant negative correlations. The maps for MoCA and Trails‐B show areas in the anterior cingulate cortex (ACC), bilateral dorsolateral prefrontal cortex (dlPFC) and bilateral parietal cortex. Trails‐B additionally revealed areas in the insular cortex and temporal cortex. For Reverse Digit Span the correlation was more widespread and also showed associations in motor and supplementary motor cortex beside dlPFC and parietal cortex.ConclusionAcross three cognitive tests we observed positive correlation with fMRI complexity in areas representing brain networks involved in executive function and memory processes. Impaired cognitive function thus is represented by reduced fMRI complexity. fMRI complexity might provide a novel imaging metric that is indicative of impaired cognitive function and is complementary to existing imaging approaches.