Differential effect of age on posterior and anterior hippocampal functional connectivity

Abstract

Aging is associated with declines in cognitive performance and multiple changes in the brain, including reduced default mode functional connectivity (FC). However, conflicting results have been reported regarding age differences in FC between hippocampal and default mode regions. This discrepancy may stem from the variation in selection of hippocampal regions. We therefore examined the effect of age on resting state FC of anterior and posterior hippocampal regions in an adult life-span sample. Advanced age was associated with lower FC between the posterior hippocampus and three regions: the posterior cingulate cortex, medial prefrontal cortex, and lateral parietal cortex. In addition, age-related reductions of FC between the left and right posterior hippocampus, and bilaterally along the posterior to anterior hippocampal axis were noted. Age differences in medial prefrontal and inter-hemispheric FC significantly differed between anterior and posterior hippocampus. Older age was associated with lower performance in all cognitive domains, but we observed no associations between FC and cognitive performance after controlling for age. We observed a significant effect of gender and a linear effect of COMT val158met polymorphism on hippocampal FC. Females showed higher FC of anterior and posterior hippocampus and medial prefrontal cortex than males, and the dose of val allele was associated with lower posterior hippocampus - posterior cingulate FC, independent of age. Vascular and metabolic factors showed no significant effects on FC. These results suggest differential age-related reduction in the posterior hippocampal FC compared to the anterior hippocampus, and an age-independent effect of gender and COMT on hippocampal FC.

Keywords: Aging; COMT val158met; Functional connectivity; Gender; Hippocampus; Vascular risk.

Figure 1

Effect of age on hippocampal – default mode functional connectivity. Age-related decreases in functional connectivity between bilateral posterior hippocampus and three other default mode network regions – posterior cingulate/retrosplenial, medial prefrontal and bilateral lateral parietal are shown in red. Functional connectivity of the anterior hippocampus to the same regions is shown in blue. The effect of age on functional connectivity with the medial prefrontal cortex is significantly different between posterior and anterior hippocampus.

Figure 2

Effect of age on hippocampal functional connectivity. Age-related decreases in inter-hemispheric functional connectivity for left – right posterior hippocampus are shown in red in the left scatterplot. The anterior hippocampus, which does not show an age effect, is shown in blue. The effect of age on inter-hemispheric functional connectivity is significantly different between posterior and anterior hippocampus. Age-related decreases in within-hemispheric functional connectivity, along the posterior to anterior axis of the hippocampus, are shown in the right scatterplot for both the left (in green) and right (in orange) hemispheres.

Figure 3

Age-independent linear effect of COMT val158met genotype on functional connectivity strength between posterior hippocampus and posterior cingulate/retrosplenial cortex. The bar graphs show the significant differences between genotypes as revealed by post-hoc comparisons. *Significant at p<0.05