Abstract Body (Do not enter title and authors here): Introduction: Brain health is dependent upon maintenance of stable cerebral blood flow in part through the interplay of blood pressure variability (BPV) and cerebrovascular reactivity (CVR). Consistent with this conceptualization, both BPV and CVR have been separately implicated in cerebral hypoperfusion and white matter lesion (WML) burden. However, the interactive effect of BPV and CVR on WML burden has yet to be investigated.

Hypothesis: Older adults with elevated BPV and deficient CVR will exhibit greater WML volume.

Aims: Determine the relationship between elevated beat-to-beat BPV and WML volume across varying levels of whole brain CVR.

Methods: Independently living older adults without history of major neurological/psychiatric history were recruited from the community and underwent continuous blood pressure monitoring and pseudo-continuous arterial spin labeling MRI. Whole brain perfusion was quantified during 5 minutes of rest with simultaneous monitoring of end-tidal CO₂ (_ETCO₂) levels. BPV was quantified as beat-to-beat systolic average real variability and spontaneous CVR was quantified as %change in CBF/change in _ETCO₂ at rest. WML volume was quantified from T1-weighted fluid attenuated inversion recovery and segmented with the lesion growth algorithm implemented in the LST toolbox version 3.0.0 for SPM12.

Results: Eighty-five older adults were studied (mean age = 69.3 years; SD = 6.56; age range 55–89 years; 61.4% female). Resting whole brain CVR moderated the relationship between BPV and WML volume (B= -.12, P= .01). Specifically, in individuals with impaired whole brain CVR, elevated BPV was independently associated with increased white matter lesion volume (Fig. 1).

Conclusion: The present findings show that the relationship between BPV and WML volume is dependent upon whole brain CVR. This suggests that the cerebral vasculature’s ability to respond to vasoactive stimuli determines whether elevated BPV is associated with white matter lesions. Future studies of blood pressure variability and cerebral small vessel disease should account for this interactive effect.