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

• 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.

PurposeTo evaluate the relationship between both dynamic and steady-state measures of cerebrovascular reactivity (CVR) and the progression of age-related white matter disease.MethodsBlood 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).ResultsIn 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 < 0.01).ConclusionsVascular impairment in regions of NAWM that progresses to WMH consists not only of decreased magnitude of ssCVR, but also a pathological decrease in the speed of vascular response. These findings support the association between cerebrovascular dysregulation and the development of WMH.