Hippocampal vascularization patterns exert local and distant effects on brain structure but not vascular pathology in old age

Abstract

The hippocampus within the medial temporal lobe is highly vulnerable to age- related pathology such as vascular disease. We examined hippocampal vascularization patterns by harnessing the ultra-high resolution of 7 Tesla MR angiography. Dual-supply hemispheres with a contribution of the anterior choroidal artery to hippocampal blood supply were distinguished from single-supply ones with a sole dependence on the posterior cerebral artery. A recent study indicated that a dual vascular supply is related to preserved cognition and structural hippocampal integrity in old age and vascular disease. Here, we examined regional specificity of these structural benefits at the level of medial temporal lobe sub- regions and hemispheres. In a cross-sectional study with an older cohort of 17 patients with cerebral small vessel disease (70.7±9.0 years, 35.5% female) and 27 controls (71.1±8.2 years, 44.4% female), we demonstrate that differences in grey matter volumes related to the hippocampal vascularization pattern were specifically observed in the anterior hippocampus and entorhinal cortex. These regions were especially bigger in dual-supply hemispheres, but also seemed to benefit from a contralateral dual supply. We further show that total grey matter volumes were greater in people with at least one dual-supply hemisphere, indicating that the hippocampal vascularization pattern has more far-reaching structural implications beyond the medial temporal lobe. A mediation analysis identified total grey matter as a mediator of differences in global cognition. However, our analyses on multiple neuroimaging markers for cerebral small vessel disease did not reveal any evidence that an augmented hippocampal vascularization conveys resistance nor resilience against vascular pathology. We propose that an augmented hippocampal vascularization might contribute to maintaining structural integrity in the brain and preserving cognition despite age-related degeneration. As such, the binary hippocampal vascularization pattern could have major implications for brain structure and function in aging and dementia independent of vascular pathology, while presenting a simple framework with potential applicability to the clinical setting.

Vascular mapping of the human hippocampus using Ferumoxytol-enhanced MRI

“…Hence, TOF-based MR angiography (MRA) provides a robust way to obtain a map of major arteries, as shown in our study using a 3T scanner. Indeed, the utilization of higher field strength (7T) has been shown to be extremely useful in improving the visualization of the arterial vasculature ( Vockert et al, 2021 , Perosa et al, 2020 , Spallazzi et al, 2019 ). On the other hand, the presence of Ferumoxytol strongly alters the magnetic properties of the blood (both T 1 and T 2 * ), which dominates the TOF effect, making it possible to visualize the smaller vessels.…”

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

“…"double supply", large arteries. Participants with a double-supplied MTL displayed better preserved temporal lobe and whole-brain gray matter volume, as well as better sustained memory and global cognitive function [50][51][52]. These results suggest that patterns of vascular supply can be considered a measure of resistance and resilience that can be observed in brain regions beyond the supplied core area.…”

Microvascular Impairment in Patients With Cerebral Small Vessel Disease Assessed With Arterial Spin Labeling Magnetic Resonance Imaging: A Pilot Study

“…The CSVD sum score was modified from Charidimou et al [CAA score, (Charidimou et al, 2016b )] and Staals et al [more specific for HA (Staals et al, 2015 )], which likewise take into account CMBs, cSS, WMHs, lacunes, and EPVSs. We combined both scores (Vockert et al, 2021 ) and extended that sum score by WMH patterns according to Charidimou et al ( 2016a ), hippocampal EPVSs and ICHs. The number of CMBs and EPVSs span a wide range of values, and their presence is currently predominantly rated on an ordinal scale like, e.g., the scale applied by Doubal et al ( 2010 ) for EPVSs or Charidimou et al for CMBs (Charidimou et al, 2016b ).…”