Longitudinal reduction in blood pressure in hypertensive individuals is associated with increased levels of biomarkers for Alzheimer's disease

In hypertension (HTN), cerebral blood flow (CBF) regulation limits are changed and the blood pressure (BP) threshold at which CBF is safely maintained is higher. This shift may increase the brain's vulnerability to hypoperfusion at lower BP. Despite growing recognition of the link between hypoperfusion and neurodegeneration little is known about whether blood pressure reductions can induce deficient perfusion and promote expression of cerebrospinal fluid (CSF) biomarkers of amyloid and neurofibrillary pathology. We investigated the relationship between longitudinal changes in mean arterial pressure (MAP) and CSF biomarkers of Alzheimer's disease in a group of cognitively healthy elderly with and without HTN. Longitudinal assessments of blood pressure (MAP), CSF p-tau181 (phosphorylated tau), total tau, amyloid ß 1-42 (Aß42), cognition and whole brain volume were conducted on average 2.0±0.6 years apart in a group of 77 cognitively healthy elderly (age 63.4±9.4, range 44-86 years; education 16.9±2.1, range 10-22 years; 60% women). MAP was calculated as: 1/3 systolic blood pressure + 2/3 of diastolic blood pressure. At baseline HTN was found in 23 individuals (30%). When longitudinal change (ˆ†) in p-tau181 was predicted with the ˆ†MAP, HTN, and the HTNxˆ†MAP interaction, both the total model (F 3,73=3.9, p=.01), and the interaction term (p=.01) were significant. These data indicate that the relationship between ˆ†MAP and ˆ†p-tau181 was strongly dependent on the presence or absence of HTN. Only in the HTN group was a decrease in MAP from baseline to follow-up related to an increase in p-tau181 (r=-0.5, p=.01). In addition, only among subjects with HTN, was a reduction in MAP related to the worsening of verbal episodic memory (r=0.46, p=.03). Finally in the entire group the increase in p-tau181 was associated with reduction in the verbal episodic memory score (ß=-.223, p=.048). No relationship was observed between changes in MAP and whole brain volume. In subjects with HTN, MAP reduction is associated with increased CSF p-tau181 and deterioration of episodic memory, possibly resulting from suboptimal perfusion and subsequent accumulation of neurofibrillary tangles. Prior experimental work has demonstrated a relationship between perfusion, energetic reductions and tauopathy.