Effect of Arterial Stiffness and Cerebral Pulsatility on Hippocampal Tissue Integrity in Healthy Adults

Abstract

Elevated large elastic artery (i.e. aorta and common carotid) stiffness has emerged as a risk factor of cognitive impairment in older adults. Stiffening of these arteries leads to increased pulsatile energy transmission into the brain, which may result in structural damage to neuronal tissue, and potentially precipitate cognitive decline. In this regard, changes to microstructural integrity of the hippocampus (HC), a brain structure essential for memory encoding, may reflect the impact of age‐related increases in arterial stiffness and pulsatile blood flow through the middle cerebral artery (MCA). Therefore, the purpose of this study was to determine whether large elastic artery stiffness and associated pulsatile hemodynamics are related with HC integrity in healthy adults across the lifespan. We included 25 participants (16M/9F, age: 44±16 y; age range: 22‐69 y; BMI: 27±5 kg/m2; BP: 115±11/71±10 mmHg) in this study. Aortic stiffness was assessed as carotid‐femoral pulse wave velocity (PWV) using applanation tonometry (AtCor Medical, Sydney, Australia). Common carotid artery (CCA) stiffness was measured using duplex ultrasound (Logiq e, GE Healthcare, Chicago, IL) and analyzed with an offline wall‐tracking software (Cardiovascular Suite, Pisa, Italy). CCA blood pressures were acquired from applanation tonometry. Transcranial Doppler ultrasound was used to measure basal mean blood flow velocity of the MCA (MCAv) from which Gosling’s pulsatility index (PI) was calculated as the difference between peak systolic MCAv and end‐diastolic MCAv over mean MCAv. HC tissue integrity was measured using magnetic resonance elastography (MRE), which was acquired using a Siemens 3T Prisma MRI scanner coupled with shear waves generated via a pneumatic actuator (Resoundant, Rochester, MN) at 50 Hz. Bilateral HC stiffness (µ) and HC damping ratio (ξ) were estimated from MRE displacement data using a nonlinear inversion algorithm. A correlation matrix was used to determine if arterial stiffness, vascular hemodynamics, and other lifestyle factors (e.g., age, sex, BMI) were related with HC integrity. BMI (r=‐0.40, p=0.048), CCA pulse pressure (PP) (r=‐0.61, p=0.001), and MCAv PI (r=‐0.48, p=0.01) were associated with HC µ while age (r=0.66, p=0.0004), BMI (r=0.45, p=0.02), SBP (r=0.52, p= 0.008), aortic PWV (r=0.65, p=0.0004), and CCA stiffness (r=0.60, p=0.002) were associated with HC ξ. Next, multiple linear regressions were performed to determine the independent associations among arterial stiffness, vascular hemodynamics of interest, and HC integrity while correcting for age and BMI. HC µ remained significantly associated with CCA PP (β=‐0.52, p=0.03) and was trending towards negative association with MCAv PI (β=‐0.37, p=0.06). There were no significant independent associations among the variables of interest and HC ξ, however, together these variables significantly explained variance in HC ξ (R2=0.37, p=0.03). Our results suggest increased pulsatile pressure through the carotid artery along with elevated cerebral pulsatility negatively impacts HC tissue integrity. Future studies should consider how our current findings affect functional outcomes like memory and age‐related neurological conditions.