1 Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
2 Physics Department, Concordia University, Montreal, Quebec H4B 1R6, Canada.
3 Department of Radiology, Université de Sherbrooke, Sherbrooke, Quebec J1G 1E4, Canada.
4 Sherbrooke Connectivity Imaging Lab (SCIL), Computer Science Department, Faculty of Science, University of Sherbrooke, Quebec J1K 0A5, Canada.
5 StoP-AD Centre, Douglas Mental Health Institute Research Centre, Montreal, Quebec H4H 1R3, Canada.
6 Department of Psychiatry, McGill University, Montreal, Quebec H3A 1A1, Canada.
7 Department of Biomedical Engineering, McGill University, Montreal, Quebec H3A 2B4, Canada.
8 Cerebral Imaging Centre, Douglas Mental Health Institute Research Centre, Montreal, Quebec H4H 1R3, Canada.
9 Department of Psychology and Institute of Gerontology, Wayne State University, Detroit, Michigan 48202.
10 Montreal Heart Institute, Montreal, Quebec H1T 1C8, Canada.
11 Department of Psychology, York University, Toronto, ON M3J 1P3, Canada.
12 Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada nathan.spreng@gmail.com.
13 Department of Neurology and Neurosurgery, Montréal Neurological Institute, Montréal, Quebec H3A 1A1, Canada.
14 Departments of Psychiatry and Psychology, McGill University, Montréal, Quebec H3A 1G1, Canada.

Elevated iron deposition in the brain has been observed in older adult humans and persons with Alzheimer's disease (AD), and has been associated with lower cognitive performance. We investigated the impact of iron deposition, and its topographical distribution across hippocampal subfields and segments (anterior, posterior) measured along its longitudinal axis, on episodic memory in a sample of cognitively unimpaired older adults at elevated familial risk for AD (N = 172, 120 females, 52 males; mean age = 68.8 ± 5.4 years). MRI-based quantitative susceptibility maps were acquired to derive estimates of hippocampal iron deposition. The Mnemonic Similarity Task was used to measure pattern separation and pattern completion, two hippocampally mediated episodic memory processes. Greater hippocampal iron load was associated with lower pattern separation and higher pattern completion scores, both indicators of poorer episodic memory. Examination of iron levels within hippocampal subfields across its long axis revealed topographic specificity. Among the subfields and segments investigated here, iron deposition in the posterior hippocampal CA1 was the most robustly and negatively associated with the fidelity memory representations. This association remained after controlling for hippocampal volume and was observed in the context of normal performance on standard neuropsychological memory measures. These findings reveal that the impact of iron load on episodic memory performance is not uniform across the hippocampus. Both iron deposition levels as well as its spatial distribution, must be taken into account when examining the relationship between hippocampal iron and episodic memory in older adults at elevated risk for AD.