Blood pressure decrease correlates with tau pathology and memory decline in hypertensive elderly

Abstract

In hypertension (HTN), cerebral blood flow regulation limits are changed, and the threshold for blood pressure (BP) at which perfusion is safely maintained is higher. This shift may increase the brain's vulnerability to lower BP in subjects with vascular disease. We investigated whether longitudinal reduction in mean arterial pressure (MAP) was related to changes in cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease in a group of cognitively healthy elderly with and without HTN. The relationships among MAP, memory decline, and hippocampal atrophy were also examined. Seventy-seven subjects (age 63.4 ± 9.4, range 44-86 years; education 16.9 ± 2.1, range 10-22 years; 60% women) were assessed twice, 2 ± 0.5 years apart. At both time points, all subjects underwent full medical and neuropsychological evaluations, lumbar punctures, and magnetic resonance imaging examinations. Twenty-five subjects had HTN. Hyper- and normotensive subjects did not differ in their CSF biomarkers, hippocampal volumes (HipVs), or memory scores at baseline. In the entire study group, the increase in tau phosphorylated at threonine 181 (p-tau(181)) was associated with a decline in verbal episodic memory (β = -0.30, p = 0.01) and HipV reduction (β = -0.27, p = 0.02). However, longitudinal decrease in MAP was related to memory decline (β = 0.50, p = 0.01) and an increase in p-tau(181) (β = -0.50, p = 0.01) only in subjects with HTN. Our findings suggest that the hypertensive group may be sensitive to BP reductions.

Keywords: CSF biomarkers; Cognition; Low blood pressure.

Figure 1

Relationships between rates of change in MAP (R_cMAP) and p-tau₁₈₁ (R_cp-tau₁₈₁) (a), rates of change in MAP and episodic verbal memory (R_cepisodic memory) (b), rates of change in episodic verbal memory and p-tau₁₈₁ (c), rates of change change in p-tau₁₈₁ and hippocampal volume (R_cHippocampal volume) (d). Solid circles and solid lines – subjects with HTN. Diamonds and dashed lines - subjects without HTN. Units in the scales represent units per year: for p-tau pg/mL/year, for MAP mmHg/year, for episodic memory z-score unit/year, for hippocampal atrophy % of intracranial volume/year.