High pulse pressure is a risk factor for prodromal Alzheimer's disease: a longitudinal study.

It has been increasingly evident that pulse pressure (PP) is associated with Alzheimer's disease (AD) but whether PP increases AD risk and the mechanism responsible for this association remains unclear. To investigate the effects of PP in the process of AD, we have evaluated the cross-sectional and longitudinal associations of PP with AD biomarkers, brain structure and cognition and have assessed the effect of PP on AD risk in a large sample (n= 1,375) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Multiple linear regression and mixed-model regression were employed in cross-sectional and longitudinal analyses respectively. Clinical disease progression was assessed using Cox proportional hazards models. High PP was associated with lower β-amyloid 42 (Aβ ₄₂ ) ( P = .015), and higher total tau (T-tau) ( P = .011), phosphorylated tau (P-tau) ( P = .003), T-tau/Aβ ₄₂ ( P = .004) and P-tau/Aβ ₄₂ ( P = .001), as well as heavier cortical amyloid-beta burden ( P = .011). Longitudinally, baseline high PP was significantly associated with hippocampal atrophy ( P = .039), entorhinal atrophy ( P = .031) and worse memory performance ( P = .058). Baseline high PP showed more rapid progression than those with normal PP ( P <.001). These results suggest PP elevation could increase AD risk, which may be driven by amyloid plaques and subclinical neurodegeneration.