Lifetime familiarity and episodic familiarity: The role of the transentorhinal cortex in aging

Objectives: The transentorhinal cortex (tErC), which includes the medial portion of the perirhinal (PrC) and the anterolateral portion of the entorhinal cortices (alErC), is among the first brain regions affected by Alzheimer’s Disease (AD). Yet, its precise cognitive role remains controversial. Recent models propose that this region supports episodic familiarity and lifetime familiarity, and that it is particularly involved in tasks requiring fine conceptual discrimination between similar objects. The present study examined episodic and lifetime familiarity across three tasks to understand how the tErC supports familiarity, using materials with varying conceptual overlap and lifetime familiarity levels in both normal and pathological aging, encompassing different levels of tErC integrity.
Methods: Fifty-eight older adults (aged 55+), including healthy individuals and patients with Mild Cognitive Impairment or subjective cognitive decline, completed familiarity tasks. tErC volume was measured via high-resolution MRI and was associated with tasks performance using repeated measures ANCOVAs or stepwise linear regressions.
Results: The tErC volume was associated with familiarity performance selectively in task conditions involving high conceptual overlap between targets and lures.
Conclusion: Results indicate that tErC integrity is selectively related to familiarity-based performance when recognition requires resolving interference between conceptually similar items. We discuss how combining tasks assessing different aspects of familiarity could help identify early cognitive decline. We suggest this approach should be tested in patients with AD biomarkers.