Examining the independent and moderating effects of arterial stiffness and cerebral blood flow on total hippocampal and hippocampal subfield volumes

Michelle Horan^1*Daniel Carey²Silvin Knight³Andrew Fagan³James Fm Meaney¹Rose Anne Kenny^1,2,3Céline De Looze³

• ¹St. James's Hospital, Dublin, Ireland
• ²Mercer’s Institute for Successful Ageing, St. James’s Hospital, Dublin, Ireland
• ³Irish Longitudinal Study on Ageing, Trinity College Dublin, Dublin, County Dublin, Ireland

Dementia is a major health issue with considerable health, social and economic costs for individuals, their families, and societies. It has long been established that there is a critical link between vascular disease and the progression to dementia in ageing adults. The hippocampus has been implicated in the development of memory decline and whole hippocampal atrophy has been identified consistently in patients with cognitive decline. Subregions of the medial temporal lobe, specifically hippocampal subfield volumes have been investigated as culprit regions that selectively atrophy in memory decline.In this study, we investigate the independent and moderating effects of increased arterial stiffness (AS) and reduced cerebral blood flow (CBF) on total hippocampal volume in a large MRI sample of community-dwelling older adults from a nationally representative population-based study, the Irish Longitudinal Study on Ageing (TILDA). In supplementary analyses, we also examine if these effects are specific to certain hippocampal subfields which are known to be vulnerable to AS and CBF alterations: the cornu-amonnis 1,3,4, subiculum, and dentate gyrus. Specifically, we test the hypotheses that (i) higher AS is associated with lower total hippocampal volumes and that (ii) reduced CBF may moderate this relationship. We also test the hypotheses that (iii) persistently higher arterial stiffness over a fouryear follow-up period and (iv) the interaction between higher arterial stiffness and low cerebral blood flow may have more significant effects on hippocampal volumes. Finally we hypothesize that these effects may be exerted maximally in the CA-1, CA-4 and subiculum subfields.