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White matter hyperintensities (WMH) observed on neuroimaging of elderly individuals are associated with cognitive decline and disability. However, the pathogenesis of WMH remains poorly understood. We observed that regions of reduced cerebrovascular reactivity (CVR) in the white matter of young individuals correspond to the regions most susceptible to WMH in the elderly. This finding prompted us to consider that reduced CVR may play a role in the pathogenesis of WMH. We hypothesized that reduced CVR precedes development of WMH.

We examined 45 subjects (age range = 50–91 years; 25 males) with moderate–severe WMH, and measured their baseline CVR using the blood oxygen level–dependent magnetic resonance imaging signal response to a standardized step change in the end‐tidal partial pressure of carbon dioxide. Diffusion tensor imaging and transverse relaxation …