Does Functional Connectivity Provide a Marker for Cognitive Rehabilitation Effects in Alzheimer’s Disease? An Interventional Study

Background: Cognitive rehabilitation (CR) is a cognitive intervention for patients with Alzheimer’s disease (AD) that aims to maintain everyday competences. The analysis of functional connectivity (FC) in resting-state functional MRI has been used to investigate the effects of cognitive interventions. Objectives: We evaluated the effect of CR on the default mode network FC in a group of patients with mild AD, compared to an active control group. Methods: We performed a three-month interventional study including 16 patients with a diagnosis of AD. The intervention group (IG) consisted of eight patients, performing twelve sessions of CR. The active control group (CG) performed a standardized cognitive training. We used a seed region placed in the posterior cingulate cortex (PCC) for FC analysis, comparing scans acquired before and after the intervention. Effects were thresholded at a significance of p < 0.001 (uncorrected) and a minimal cluster size of 50 voxels. Results: The interaction of group by time showed a higher increase of PCC connectivity in IG compared to CG in the bilateral cerebellar cortex. CG revealed widespread, smaller clusters of higher FC increase compared with IG. Across all participants, an increase in quality of life was associated with connectivity increase over time in the bilateral precuneus. Conclusions: CR showed an effect on the FC of the DMN in the IG. These effects need further study in larger samples to confirm if FC analysis may suit as a surrogate marker for the effect of cognitive interventions in AD.