Familiarity-Related Processes and the Transentorhinal Cortex Volume: Insights into the Cognitive Functions of an Early Site of Alzheimer’s Pathology

Objectives: The transentorhinal cortex (tErC), which includes the medial portion of the perirhinal and the anterolateral portion of the entorhinal cortices, 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 (i.e., the sense of recognizing something based on a specific prior encounter) and lifetime familiarity (i.e., the gradual accumulation of familiarity with object concepts over the course of one's life), 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. Exploratory cluster analysis identified three subgroups: one mostly composed of healthy individuals, another including mainly patients with memory impairment, and a third heterogeneous group. The latter group relied on familiarity to compensate for impaired recollection but committed more false alarms and showed reduced accuracy as conceptual overlap increased.
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.