Aging Along the Hippocampal Axis : Structure, Function and Whole-brain Connections in Association with Memory

Abstract: Hippocampus-dependent functions display marked reductions in older age, an observation that has led to the extensive study of age effects on hippocampal properties. Even though research indicates that the hippocampus is structurally and functionally heterogeneous along its longitudinal axis, its anterior and posterior regions differentially supporting episodic and spatial memory representations, few studies explicitly consider age effects in relation to axis. Relatedly, as men and women commonly differ in episodic and spatial memory performance, and sometimes also in rates of age-related hippocampal atrophy, sex could be a potential modifier of age effects. The aim of this thesis was therefore to assess age effects on the hippocampus and its role in episodic and spatial memory across young (20-35 years), middle-aged (40-50 years) and older (60-70 years) adults, adopting a longitudinal-axis approach while considering interactions with sex. Study I evaluated hippocampal volume and activation in relation to associative memory across middle-aged and older adults. Age differences in associative memory were largest in men and paralleled by smaller volumes and less activation in the anterior hippocampus. Study II assessed hippocampus-dependent network-like organization of gray matter by measures of structural whole-brain covariance. The anterior and posterior hippocampus showed shared and distinct patterns of covariance, which were qualitatively comparable across age groups. However, participants’ expression of these patterns decreased as a function of age, comparably for men and women, and showed significant associations with episodic memory. Study III investigated age effects on resting-state functional connectivity and demonstrated that both the anterior and posterior hippocampus decreased in connectivity with several brain regions across middle-aged and older adults. Memory was only associated with age-related connectivity of the posterior hippocampus: episodic memory negatively with connectivity increasing as a function of age, and spatial memory positively with connectivity that decreased. These studies demonstrate distinct effects of age on the anterior and posterior hippocampus, and show that age-related decline of these regions differentially relates to episodic and spatial memory. Overall, findings highlight the importance of explicitly considering the heterogeneity of the hippocampal axis in the assessment of its role in age-related memory decline.