Lower hippocampal volumes at baseline are associated with higher volume loss in healthy elderly

Vivian Schultz^1,2*Benita Schmitz-Koep^1,2Aurore Menegaux^1,2Melissa Thalhammer^1,2Severin Schramm^1,2Su Hwan Kim^1,2Claus Zimmer^1,2Christian Sorg^1,2,3Panteleimon Giannakopoulos^4,5Marie-Louise Montandon^4,6Cristelle Rodriguez^4,5Sven Haller^10,7,8,9Dennis M. Hedderich^1,2

• ¹Institute for Neuroradiology, TUM University Hospital, Technical University of Munich, School of Medicine and Health, Munich, Germany
• ²TUM-NIC Neuroimaging Center, Technical University of Munich, School of Medicine and Health, Munich, Germany
• ³Department of Psychiatry, TUM University Hospital, Technical University of Munich, School of Medicine and Health, Munich, Germany
• ⁴Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland
• ⁵Division of Institutional Measures, Medical Direction, Geneva University Hospitals, Geneva, Switzerland
• ⁶Department of Rehabilitation and Geriatrics, Geneva University Hospitals, University of Geneva, Geneva, Switzerland
• ⁷CIMC - Centre d’Imagerie Médicale de Cornavin, Geneva, Switzerland
• ⁸Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden
• ⁹Faculty of Medicine of the University of Geneva, Geneva, Switzerland
• ¹⁰Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Introduction: Hippocampal volume loss occurs physiologically with age, but an accelerated rate of volume loss is linked to neurodegenerative diseases. While evidence suggests that cross-sectional study designs tend to underestimate hippocampal atrophy rates compared to longitudinal approaches, few studies have directly examined the relationship between these two methods in the context of brain aging. This study aims to investigate the association between baseline hippocampal z-scores and hippocampal volume loss over time in a cohort of healthy older adults. Methods: 182 healthy elderly subjects (mean age: 73.4 ± 3.5 years) who underwent structural MRI at two timepoints (mean time between the scans 4.8 ± 1.0 years) were included. A subset of participants (n = 103) also completed PET amyloid imaging. Hippocampal volumes were measured at baseline and follow-up using FreeSurfer (v7.1.1). Baseline volumes were adjusted for age and intracranial volume (ICV) and converted into z-scores. The annualized percent change (APC) in hippocampal volume was calculated for each participant. Neuropsychological assessments were conducted at baseline, 18, and 54 months, and APOE genotyping was performed. Correlation analyses examined the relationship between baseline hippocampal volumes and APC, while multiple regression models explored potential influencing factors. Results: Hippocampal volumes decreased from baseline to follow-up (mean APC (SD): right -1.34% (0.94), left: -1.79% (1.00)). Small, but statistically significant positive correlations were found between baseline hippocampal z-scores and APC of hippocampal volumes over time, indicating that the lower the volume at baseline, the greater the atrophy rate to timepoint two (right hippocampus: r = 0.17, p = 0.01; left hippocampus: r = 0.14, p = 0.03). No covariates significantly influenced this association (p > 0.05).Lower baseline hippocampal z-scores are associated with a greater rate of hippocampal atrophy to the follow-up examination. If validated in larger cohorts, these findings could help establish cut-off values for pathological atrophy in cross-sectional studies.