Impaired dynamic cerebrovascular response to hypercapnia predicts development of white matter hyperintensities

Purpose To evaluate the relationship between both dynamic and steady-state measures of cerebrovascular reactivity (CVR) and the progression of age-related white matter disease. Methods Blood oxygen level-dependent (BOLD) MRI CVR scans were acquired from forty-five subjects (age range: 50–90 years, 25 males) with moderate to severe white matter disease, at baseline and one-year follow-up. To calculate the dynamic (τ) and steady-state (ssCVR) components of the BOLD signal response, the PETCO2 signal waveform was convolved with an exponential decay function. The τ corresponding to the best fit between the convolved PETCO2 and BOLD signal defined the speed of response, and the slope of the regression between the convolved PETCO2 and BOLD signal defined ssCVR. ssCVR and τ were compared between normal-appearing white matter (NAWM) that remains stable over time and NAWM that progresses to white matter hyperintensities (WMHs). Results In comparison to contralateral NAWM, NAWM that progressed to WMH had significantly lower ssCVR values by mean (SD) 46.5 (7.6)%, and higher τ values by 31.9 (9.6)% (both P
Highlights • Vascular responses are slower in normal white matter that progresses to disease. • Steady-state cerebrovascular reactivity is reduced in normal white matter that progresses to disease. • Cerebrovascular dysregulation occurs before development of leukoaraiosis.