Blood pressure variability, central autonomic network dysfunction and cerebral small vessel disease in APOE4 carriers

Abstract

AbstractBackgroundIncreased blood pressure variability (BPV) is a risk factor for cerebral small vessel disease (CSVD) and neurodegeneration, independent of age and average blood pressure, particularly in apolipoprotein E4 (APOE4) carriers. However, it remains uncertain whether BPV elevation is a cause or a consequence of vascular brain injury, or to what degree injury to the central autonomic network (CAN) may contribute to BPV-associated risk inAPOE4carriers.MethodsIndependently living older adults (n=70) with no history of stroke or dementia were recruited from the community and underwent 5 minutes of resting beat-to-beat blood pressure monitoring, genetic testing, and brain MRI. Resting BPV,APOEgenotype, CSVD burden on brain MRI, and resting state CAN connectivity by fMRI were analyzed. Causal mediation and moderation analysis evaluated BPV and CAN effects on CSVD inAPOE4carriers (n=37) and non-carriers (n=33).ResultsHigher BPV was associated with the presence and extent of CSVD inAPOE4carriers, but not non-carriers, independent of CAN connectivity (B= 18.92,P= .02), and CAN connectivity did not mediate the relationship between BPV and CSVD. InAPOE4carriers, CAN connectivity moderated the relationship between BPV and CSVD, whereby BPV effects on CSVD were greater in those with lower CAN connectivity (B= 36.43,P= .02).ConclusionsOlderAPOE4carriers with higher beat-to-beat BPV exhibit more extensive CSVD, independent of average blood pressure, and the strength of CAN connectivity does not mediate these effects. Findings suggest increased BPV is more likely a cause, not a consequence, of CSVD. BPV is more strongly associated with CSVD inAPOE4carriers with lower rsCAN connectivity, suggesting CAN dysfunction and BPV elevation may have synergistic effects on CSVD. Further studies are warranted to understand the interplay between BPV and CAN function inAPOE4carriers.