Dopaminergic sub-network connectivity alterations are associated with postoperative cognitive dysfunction: Results from the BioCog cohort study

Postoperative cognitive dysfunction (POCD) is a detrimental complication after surgery with lasting impact on the patients’ daily life. It is most common after postoperative delirium. Dopaminergic dysfunction has been suggested to play a role in delirium, but little knowledge exists regarding its relevance for POCD. We hypothesized that POCD is associated with altered resting-state functional connectivity of the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNc) in functional magnetic resonance imaging (fMRI) before surgery and at postoperative follow-up after three months. Patients ≥65 years old underwent resting-state fMRI and neuropsychological assessment before major elective surgery and at follow-up three months later. POCD was determined as the reliable change index. Connectivity between VTA or SNc and 132 regions were calculated. Principal component analysis (PCA) was used for sub-network construction, and components explaining >5% of variance were retained for analysis. To study postoperative changes in patients with POCD, we applied the same transformation to postoperative connectivity, and multi-factor analysis. Regression analyses were used to describe connectivity alterations while adjusting for age, sex, MMSE, surgery and anaesthesia. Of 214 patients, 26 (12%) developed POCD. Among 132 principal components, four components for VTA- and SNc-FC were selected for further analysis. For both VTA and SNc connectivity, one component was significantly associated with POCD. Postoperative alterations of dopaminergic networks were observed in an exploratory voxel-wise analysis in a left temporal cluster. Higher dopaminergic connectivity to regions associated with spatial perceptive processes and lower connectivity to cognitive control-related areas may predispose to POCD. SIGNIFICANCE STATEMENT Delirium affects around 20% of older adults after surgery, with 30% developing lasting memory and attention issues (postoperative cognitive dysfunction, or POCD). While antidopaminergic drugs are used to treat delirium, they do not prevent long-term problems. To explore dopamine’s role in cognitive issues after delirium, we used MRI scans before and after surgery. We found that in patients who later developed POCD, dopamine-related brain regions communicated differently before surgery compared to those who did not develop POCD. These changes appear to be chronic, meaning delirium treatments may have little effect on long-term cognitive problems.