Cerebral hemodynamics to acute exercise in Veterans with Gulf War Illness

Abstract

Introduction: Gulf War Illness (GWI) is a chronic multisymptom illness (CMI) affecting approximately one third of Veterans deployed to the Persian Gulf War (GW). A characteristic feature of GWI is post-exertional malaise (PEM), where symptoms worsen following physical and/or mental exertion. The pathophysiology of PEM remains unknown, yet an emerging area of research has focused on cerebral blood flow (CBF) regulation in GWI and its possible role in disease pathophysiology. Purpose: To investigate CBF regulation in Veterans with GWI prior to and following an acute bout of aerobic exercise, and to explore its relationship to symptom outcomes. Methods: Veterans with GWI (n = 45) and healthy GW Veteran controls (n = 34) completed symptom questionnaires and CBF testing prior to and following a submaximal exercise test (30-minutes at 70  5% of age-predicted heart rate reserve). Symptom responses post-exercise were quantified using a symptom score metric derived from the Kansas Symptom Inventory. Autoregulatory indices (ARI) were calculated from sit-to-stand tests as a measure of dynamic cerebral autoregulation. Cerebrovascular reactivity (CVR) was assessed via hypercapnic (8% CO2) and hypocapnic (hyperventilation protocol) stimulation and quantified using reactivity slopes. Linear mixed effects models were used to test differences in CBF regulation between groups, pre- to post-exercise. Stepwise linear regression models assessed the relationship between changes in CBF regulation and symptoms outcomes. Results: Veterans with GWI reported worse baseline health (Hedge’s g: 1.34 - 1.96; p < 0.05) and a higher peak rating of perceived exertion during exercise (Hedge’s g = -0.47; p = 0.04). Linear mixed effect models revealed a significant Group x Time interaction for ARI (p < 0.05) that was not present for CVR to hypercapnia or hypocapnia. Decreases in ARI from pre- to post-exercise were significantly (p < 0.05) associated with higher neurologic symptom scores and lower mood symptom scores in Veterans with GWI. Conclusion: Acute exercise led to a decrease in dynamic cerebral autoregulation in Veterans with GWI that was not seen in healthy GW Veteran controls. Such decreases were associated with worse neurologic, fatigue, and cognitive symptoms following exercise. Further studies are needed to clarify these findings, particularly exploring CBF regulation in the sub-acute (0 - 24 hours) following exercise in Veterans with GWI.