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.

BackgroundThe association between cerebral blood supply and cognition has gained increasing interest, considering the remarkable anatomical variability of the circle of Willis. Thus, qualitative classifications of the arteries contributing to the hippocampal supply has been performed in previous studies to determine whether the additional presence of vessels might translate into cognitive differences and cerebral structural changes when coexisting with vascular pathology, to the extent of constituting a cognitive reserve. Nevertheless, the promising results in these regards are not without controversy. Hence, Vessel Distance Mapping (VDM) is here introduced, in order to ascertain the correlation of VDM‐metrics with each other and with cognitive status, as well as to elucidate which metrics have the greatest impact on cognition.MethodA battery of cognitive tests was used (including ADAScog and MoCA) in 51 subjects (71 ± 8.5yrs) with (n=20) and without (n=31) cerebral small vessel disease. Their hippocampal‐related vessels were manually segmented by using high‐resolution 7T Time‐of‐Flight‐MRI. Vessel distance maps were generated by computing the distances of each voxel to its nearest vessel, obtaining 3 VDM‐metrics: global‐VDM (vessel density surrogate), VS‐VDM (vessel‐specific supply), and COMD (distance to the center of mass, reflecting vessel distribution). Hippocampal masks were used to assess the whole and subregional hippocampus. Regression models were applied for evaluating the interrelation among the metrics, and their association with cognition.ResultHigh correlations were observed for intra‐metric comparisons, as well as when comparing whole hippocampal vs. sub‐hippocampal metrics. Greater values of VDM‐metrics reflecting higher distances among vessels were associated with poorer cognitive outcomes only in subjects affected by vascular pathology (global‐VDM R²=0.7248, p=0.0054; COMD R²=0.7248, p=0.0013). Metrics revealing vascular distribution (p=0,0053) and density (p=0,0169) were the most influential on cognition, and in this context those for the whole hippocampus predominated over the subregional ones.ConclusionA mixed contribution of vessel distribution and density is proposed to confer cognitive resilience, in a way consistent with anatomical fundamentals and with previous research findings. VDM provides a new, structure‐driven approach on which to raise new questions supported by the statistical robustness of a quantitative method with potential clinical implications.

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