Associations between vascular regulation and affective symptoms in cerebral small vessel disease

Abstract Background: To explore associations between selected neurovascular network (NVN) parameters, including autonomic function, cerebral autoregulation, and neurovascular coupling, and anxious and depressive symptoms in cerebral small vessel disease (CSVD). Methods: This cross-sectional study included 90 CSVD patients. Anxious and depressive symptoms were assessed using the Hamilton Anxiety (HAMA) and Hamilton Depression (HAMD) rating scales. NVN was evaluated using heart rate variability, transfer function analysis of dynamic cerebral autoregulation at rest and during handgrip, and haemodynamic responses to the Stroop test. Univariable and simplified multivariable logistic regression were performed, with false discovery rate (FDR) correction, Firth penalised regression, and exploratory receiver-operating-characteristic (ROC) analyses with bootstrap optimism correction. Results: Anxious symptoms occurred in 14 participants (15.6%) and depressive symptoms in 31 (34.4%), with substantial overlap (10 of 14 anxious participants also had depression). After FDR correction, no univariable NVN association remained significant. In simplified models, a greater blood pressure increase during Stroop Stage 3 was nominally associated with anxious symptoms after adjustment for age, sex, and coexisting depressive symptoms. Lower very-low-frequency phase in the left hemisphere during handgrip showed the most consistent nominal association with depressive symptoms, including after adjustment for coexisting anxious symptoms. Exploratory ROC analyses suggested apparent discrimination, but optimism-corrected estimates and the absence of external validation preclude any clinical screening interpretation. Conclusions: Selected NVN parameters showed nominal, potentially differential associations with anxious and depressive symptoms in CSVD. Given symptom overlap, few events, multiple testing, and no external validation, these findings are hypothesis-generating and require confirmation in larger longitudinal cohorts. Trial registration: Chinese Clinical Trial Registry, ChiCTR2100043346; registered on 11 February 2021. Retrospectively registered.