A pathway linking pulse pressure to dementia in adults with Down syndrome
Batool Rizvi, Patrick J Lao, Mithra Sathishkumar, Lisa Taylor, Nazek Queder, Liv McMillan, Natalie Edwards, David B Keator, Eric Doran, Christy Hom, Dana Nguyen, H Diana Rosas, Florence Lai, Nicole Schupf, Jose Gutierrez, Wayne Silverman, Ira T Lott, Mark Mapstone, Donna M Wilcock, Elizabeth Head, Michael A Yassa, Adam M BrickmanAbstract
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 and is linked to a diagnosis of dementia in adults with DS via structural imaging markers of cerebrovascular disease and atrophy. The study included participants with DS from the Biomarkers of Alzheimer’s Disease in Adults with Down Syndrome study (ADDS; n=195, age=50.6+7.2 years, 44% women, 18% diagnosed with dementia). Higher pulse pressure was associated with greater global, parietal, and occipital white matter hyperintensity (WMH) volume but not to enlarged perivascular spaces (PVS), microbleeds, or infarcts. Through a structural equation model, we found that pulse pressure was associated with greater WMH volume, which in turn was related to increased neurodegeneration, and subsequent dementia diagnosis. Pulse pressure is an important determinant of brain health and clinical outcomes in individuals with DS despite the low likelihood of frank hypertension.