Successful cognitive aging is associated with thicker anterior cingulate cortex and lower tau deposition compared to typical aging

Abstract

Introduction: There is no consensus on either the definition of successful cognitive aging (SA) or the underlying neural mechanisms.

Methods: We examined the agreement between new and existing definitions using: (1) a novel measure, the cognitive age gap (SA-CAG, cognitive-predicted age minus chronological age), (2) composite scores for episodic memory (SA-EM), (3) non-memory cognition (SA-NM), and (4) the California Verbal Learning Test (SA-CVLT).

Results: Fair to moderate strength of agreement was found between the four definitions. Most SA groups showed greater cortical thickness compared to typical aging (TA), especially in the anterior cingulate and midcingulate cortices and medial temporal lobes. Greater hippocampal volume was found in all SA groups except SA-NM. Lower entorhinal ¹⁸ F-Flortaucipir (FTP) uptake was found in all SA groups.

Discussion: These findings suggest that a feature of SA, regardless of its exact definition, is resistance to tau pathology and preserved cortical integrity, especially in the anterior cingulate and midcingulate cortices.

Highlights: Different approaches have been used to define successful cognitive aging (SA). Regardless of definition, different SA groups have similar brain features. SA individuals have greater anterior cingulate thickness and hippocampal volume. Lower entorhinal tau deposition, but not amyloid beta is related to SA. A combination of cortical integrity and resistance to tau may be features of SA.

Keywords: Alzheimer's disease; PET; amyloid; biomarkers; cortical thickness; exceptional cognitive performance; successful aging; superaging; tau.