Relationship between hippocampal subfield volumes and cognitive decline in healthy subjects

Simon Doran; Daniel Carey; Silvin Knight; James F Meaney; Rose Anne Kenny; Céline De Looze

doi:10.3389/fnagi.2023.1284619

Relationship between hippocampal subfield volumes and cognitive decline in healthy subjects

Front Aging Neurosci. 2023 Dec 7:15:1284619. doi: 10.3389/fnagi.2023.1284619. eCollection 2023.

Authors

Simon Doran^{1

2}, Daniel Carey³, Silvin Knight³, James F Meaney^{1

2}, Rose Anne Kenny^{3

4}, Céline De Looze³

Affiliations

¹ Department of Radiology, St James's Hospital, Dublin, Ireland.
² The Thomas Mitchell Centre for Advanced Medical Imaging, St James's Hospital, Dublin, Ireland.
³ The Irish Longitudinal Study on Ageing, School of Medicine, Trinity College Dublin, Dublin, Ireland.
⁴ The Mercer's Institute for Successful Ageing (MISA), St James's Hospital, Dublin, Ireland.

Abstract

We examined the relationship between hippocampal subfield volumes and cognitive decline over a 4-year period in a healthy older adult population with the goal of identifying subjects at risk of progressive cognitive impairment which could potentially guide therapeutic interventions and monitoring. 482 subjects (68.1 years +/- 7.4; 52.9% female) from the Irish Longitudinal Study on Ageing underwent magnetic resonance brain imaging and a series of cognitive tests. Using K-means longitudinal clustering, subjects were first grouped into three separate global and domain-specific cognitive function trajectories; High-Stable, Mid-Stable and Low-Declining. Linear mixed effects models were then used to establish associations between hippocampal subfield volumes and cognitive groups. Decline in multiple hippocampal subfields was associated with global cognitive decline, specifically the presubiculum (estimate -0.20; 95% confidence interval (CI) -0.78 - -0.02; p = 0.03), subiculum (-0.44; -0.82 - -0.06; p = 0.02), CA1 (-0.34; -0.78 - -0.02; p = 0.04), CA4 (-0.55; -0.93 - -0.17; p = 0.005), molecular layer (-0.49; -0.87 - -0.11; p = 0.01), dentate gyrus (-0.57; -0.94 - -0.19; p = 0.003), hippocampal tail (-0.53; -0.91 - -0.15; p = 0.006) and HATA (-0.41; -0.79 - -0.03; p = 0.04), with smaller volumes for the Low-Declining cognition group compared to the High-Stable cognition group. In contrast to global cognitive decline, when specifically assessing the memory domain, cornu ammonis 1 subfield was not found to be associated with low declining cognition (-0.14; -0.37 - 0.10; p = 0.26). Previously published data shows that atrophy of specific hippocampal subfields is associated with cognitive decline but our study confirms the same effect in subjects asymptomatic at time of enrolment. This strengthens the predictive value of hippocampal subfield atrophy in risk of cognitive decline and may provide a biomarker for monitoring treatment efficacy.

Keywords: MRI; cognitive decline; dementia; hippocampus subfields; risk factors.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Funding for The Irish Longitudinal Study on Ageing (TILDA) is provided by the Irish Government, the Health Research Board (HRB), The Atlantic Philanthropies, and the Irish Life Plc.