Faculty Bibliography

Background: 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. Methods: Longitudinal assessments of blood pressure (MAP), CSF ptau181 (phosphorylated tau), total tau, amyloid beta 1-42 (Abeta42), cognition and whole brain volume were conducted on average 2.060.6 years apart in a group of 77 cognitively healthy elderly (age 63.469.4, range 44-86 years; education 16.962.1, range 10-22 years; 60% women). MAP was calculated as: 1/3 systolic blood pressure + 2/3 of diastolic blood pressure. Results: At baseline HTN was found in 23 individuals (30%). When longitudinal change (y) in p-tau181 was predicted with theyMAP, HTN, and the HTNxyMAP 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 yMAP and yp-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 (beta=-.223, p=.048). No relationship was observed between changes in MAP and whole brain volume. Conclusions: 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

Resistant hypertension is common among adults with hypertension affecting up to 30% of patients. The treatment of resistant hypertension is important because suboptimal blood pressure control is the leading preventable cause of death worldwide. A frequent comorbid condition in patients with resistant hypertension is obstructive sleep apnea. The pathophysiology of sleep apnea-associated hypertension is characterized by sustained adrenergic activation and volume retention often posing treatment challenges in patients with resistant hypertension. This review will address some of the epidemiologic data associating apnea with the pathogenesis of resistant hypertension. Diagnosis and management of apnea and its associated hypertension will also be considered