Dopaminergic network connectivity alterations are associated with postoperative cognitive dysfunction

Postoperative cognitive dysfunction (POCD) is a detrimental complication after surgery with a 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 dimensionality reduction in preoperative connectivity, 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. No postoperative alterations of dopaminergic networks were associated with POCD.

Altered preoperative functional connectivity of the dopaminergic system predisposes to POCD. Particularly relevant regions are associated with sensory, especially spatial perception and higher cognitive functions.

HIGHLIGHTS

• Dopaminergic dysfunction is a hallmark ofdelirium

• No evidence for postoperative cognitive dysfunction (POCD)

• Methods: resting-state functional connectivity of the VTA and SNc

• Connectivity alterations of the VTA and SNc predispose for POCD

• Affected areas involed in perception, spatial processing and cognition