Abstract
Individual differences in memory during aging are associated with the microstructure of the fornix, a bidirectional tract connecting the hippocampus with the diencephalon, basal forebrain and cortex. To investigate the origin of alterations in fornix microstructure, measurement of hippocampal subfield volumes was combined with diffusion MRI and cognitive evaluation in a new sample of 31 healthy human participants aged 50–89 years. The fornix, uncinate and parahippocampal cingulum were reconstructed using diffusion MRI tractography. Episodic memory was assessed with free and cued verbal recall, visual recognition and paired associate learning tests. Recall performance was associated with fornix microstructure and hippocampal subfield volumes. Subiculum and CA1 volumes remained positively associated with fornix microstructure when controlling for other volumes. Subiculum volume was also associated with fornix microstructure independent of age. Regression analyses showed that subiculum-fornix associations explained more variation in recall than that of CA1-fornix associations. In a multivariable regression model, age and subiculum volume were independent predictors of free recall whilst fornix microstructure and CA1 volume were not. These results suggest that age-related changes in a network that includes the subiculum and fornix are important in cognitive change in healthy aging. These results match anatomical predictions concerning the importance of hippocampal – diencephalic projections for memory.
Highlights
The decline of episodic memory is a common but variable accompaniment of aging
In a previous diffusion Magnetic Resonance Imaging (MRI) study, we demonstrated that microstructure of the fornix – a bidirectional tract that links the hippocampal formation with the diencephalon, basal forebrain and cortex – was the main
There was a close relationship between subiculum volume and microstructure of the fornix and this relationship was relevant to memory performance, significantly more so than the relationship between CA1 and fornix microstructure
Summary
The decline of episodic memory is a common but variable accompaniment of aging. Subiculum-Fornix Connectivity in Memory correlate of recollection in healthy older adults, as measured by tests of free recall (Metzler-Baddeley et al, 2011). This association is lost, when the fornix is damaged in incipient AD (Metzler-Baddeley et al, 2012b). Fornix microstructure accounts for variation in memory performance not associated with chronological age. Fornix microstructure correlated with episodic recollection in a group of young adults in a narrow age range (Rudebeck et al, 2009)
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