Individuals with Down syndrome (DS) are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease, entorhinal cortical atrophy, and diagnosis of dementia in adults with DS. Participants with DS from the Biomarkers of Alzheimer's Disease in Adults with Down Syndrome study (ADDS; n = 195, mean age (SD) = 50.6 (7.2), 44% women, 18% diagnosed with dementia) were included. Higher pulse pressure was associated with greater global, parietal, and occipital WMH volume. Pulse pressure was not related to enlarged PVS, microbleeds, infarcts, entorhinal cortical thickness, or dementia diagnosis. However, in a serial mediation model, we found that pulse pressure was indirectly related to dementia diagnosis through parieto-occipital WMH and, subsequently through entorhinal cortical thickness. Higher pulse pressure may be a risk factor for dementia in people with DS by promoting cerebrovascular disease, which in turn affects neurodegeneration. Pulse pressure is an important determinant of brain health and clinical outcomes in individuals with Down syndrome despite the low likelihood of frank hypertension.

Michael A. Yassa has received consulting fees from Eisai Cognito Therapeutics, LLC, CuraSen Therapeutics, Inc, and Enthorin Therapeutics, LLC. Adam M. Brickman has received consulting fees from Keystone Heart, Regeneron, Cognition Therapeutics, and Flomenhaft Law firm.

This research was supported by grants from the National Institutes of Health (NIA U01 AG051412, U19 AG068054, RF1 AG079519).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the institutional review boards of Columbia University, Massachusetts General Hospital, and University of California, Irvine, and written informed consent was obtained from the participants and/or their legal guardian or legally authorized representative.

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Data in the current study came from the Alzheimer's Biomarker Consortium - Down Syndrome (ABC-DS) study. Data from the ABC-DS can be requested here: https://www.nia.nih.gov/research/abc-ds#data