Lifetime familiarity and episodic familiarity: The role of anterior medial temporal lobe cortices in aging

The perirhinal (PrC) and anterolateral entorhinal cortex (alErC) are among the first brain regions affected by Alzheimer’s Disease (AD). Yet, their precise cognitive role remains unclear. Recent models propose that these regions support episodic familiarity and lifetime familiarity in tasks requiring fine conceptual discrimination. Evidence in aging and AD is however lacking. We assessed episodic (Task 1) and lifetime familiarity judgments (Task 2) using materials with varying levels of conceptual overlap and lifetime familiarity for targets and lures (Task 3) in normal and pathological aging. Fifty-eight older adults (aged 55+), including healthy individuals and patients with Mild Cognitive Impairment or Subjective Cognitive Decline, completed familiarity tasks. PrC and alErC volumes were measured via high-resolution MRI and correlated with tasks performance. The PrC and alErC volumes were linked with both episodic and lifetime familiarity, but only when fine conceptual discrimination was needed. Exploratory cluster analysis identified three subgroups: one composed of healthy individuals, another including majoritarily patients with memory impairment, and a third, more heterogeneous group, potentially representing early cognitive decline. The latter group relied on familiarity to compensate for impaired recollection but committed more false alarms and showed reduced accuracy as conceptual overlap increased. The results support the role of the PrC/alErC in mediating familiarity for fine representations. We also discuss how combining tasks that assess different aspects of familiarity could help identify early cognitive decline and suggest that this approach should be tested in patients with amyloid biomarkers of AD.