Author Response: White Matter Hyperintensities Mediate the Association of Nocturnal Blood Pressure With Cognition

We would like to thank Fisher et al. for their comment on our study1 and apologize for failing to cite their important paper2 in our work. We agree that white matter hyperintensity volumes in periventricular and deep regions are typically highly correlated, and we speculate that the reason we observed regional effects whereas Paganini-Hill and colleagues did not was due to age differences between our samples. White matter hyperintensities are typically more prominent in periventricular regions at early ages and become more diffuse with age.3 Our participants were, on average, 30 years younger than those included in the report of Paganini-Hill et al.; we may have captured the earliest white matter changes, which may have greater regional specificity in terms of their clinical correlates. We also agree that tract-specific analysis of white matter hyperintensities will provide greater insight into the effects of this damage on cognition, and recent work4,5 further supports this as a promising line of inquiry. In addition to the comment regarding the timing of hypertension medications, we would also emphasize that the frequency of ambulatory blood pressure measurements—particularly multiple times per hour6—plays an important role in the diagnostic value of these measurements, and further work is needed to determine the optimal number and overall timescale of ambulatory blood pressure assessment. Given the similar findings between our 2 groups, we concur that the use of nighttime blood pressure variability is an important marker of vascular health.

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