Brain Events Underlying Episodic Memory Changes in Aging: A Longitudinal Investigation of Structural and Functional Connectivity

Abstract

Episodic memories are established and maintained by close interplay between hippocampus and other cortical regions, but degradation of a fronto-striatal network has been suggested to be a driving force of memory decline in aging. We wanted to directly address how changes in hippocampal-cortical versus striatal-cortical networks over time impact episodic memory with age. We followed 119 healthy participants (20-83 years) for 3.5 years with repeated tests of episodic verbal memory and magnetic resonance imaging for quantification of functional and structural connectivity and regional brain atrophy. While hippocampal-cortical functional connectivity predicted memory change in young, changes in cortico-striatal functional connectivity were related to change in recall in older adults. Within each age group, effects of functional and structural connectivity were anatomically closely aligned. Interestingly, the relationship between functional connectivity and memory was strongest in the age ranges where the rate of reduction of the relevant brain structure was lowest, implying selective impacts of the different brain events on memory. Together, these findings suggest a partly sequential and partly simultaneous model of brain events underlying cognitive changes in aging, where different functional and structural events are more or less important in various time windows, dismissing a simple uni-factorial view on neurocognitive aging.

Keywords: aging; longitudinal; memory; resting-state functional connectivity; structural connectivity.

Figure 1.

Cortico-subcortical FC patterns. Resting-state FC (FC) between the 3 seed structures and the cerebral cortex. FC was computed as the mean of the 2 time points. Massive positive relationships were observed, so the maps were z-transformed to allow inspections of regions of relatively higher (red-yellow) versus lower (blue-cyan) FC.

Figure 2.

Overlapping cortico-subcortical FC patterns. A conjunction map was created to illustrate degree of overlapping versus unique FC patterns for each seed structure, for each seed structure from Figure 1 thresholded at z ≥ 1.

Figure 3.

Age–change interactions .The maps show effects of age group on FC change. Blue-cyan indicates more negative change in the group of younger versus older participants, corrected for multiple comparisons by Monte Carlo simulations. The scatterplots illustrate mean difference in FC (z-transformed correlations) for each participant from selected regions shown in green (hippocampus), red (caudate), or yellow (putamen). The regions were selected to be representative of the effects shown in the surface maps. Mean and 95% confidence interval of the mean are shown as solid and dotted lines, respectively.

Figure 4.

Maps of the significant relationships between FC change and memory change. The 3 main columns represent the hippocampus, caudate, and putamen as seeds, respectively. The 3 main rows represent the young group, the older group, and the age interactions, for example, the effect of age on the relationship between FC change and memory change. Within each main row, each line represents learning, 5-min recall, and 30-min recall, respectively. The results were corrected for multiple comparisons by Monte Carlo simulations.

Figure 5.

rsFC–memory relationships. Scatterplots illustrating the relationship between change in memory scores between time points and change in rsFC. The rsFC data are extracted from the significant age-interaction analyses for the right hemisphere showed in Figure 4. Left panel: caudate-cortical rsFC change versus learning change. Middle panel: caudate-cortical rsFC change versus 5-min recall. Right panel: hippocampal-cortical rsFC change versus 30-min recall change.

Figure 6.

Unique and common patterns of FC–memory change relationships. Conjunction maps of the significant right hemisphere age interactions in Figure 4. The figure shows that age affected the effect of caudate FC change on learning across large regions of the cortex, overlapping with effects of hippocampal FC change in minor regions only. In contrast, for 30-min recall, age affected the hippocampal FC effect on recall only. Thus, caudate FC change and hippocampal FC change impacted different aspects of memory function across age groups.

Figure 7.

Structural connectivity tracts of interest. Four relevant white matter tracts were delineated by the use of TRACULA: superior longitudinal fasciculus temporal part (SLF temporal), cingulate gyrus, angular bundle, and uncinated fasciculus. Tract endings were projected into the cortex (blue) for visualization purposes, whereas the delinated tracts in the white matter are shown in red.

Figure 8.

Timing of influence of FC on memory change. The figure illustrates that the relationship between FC change and memory is strongest in the time periods where rate of change of a given structure typically is the lowest. Imposed on the color scale depicting the strength of the relationship between FC change and memory change, the black lines show the typical age trajectory of the volume of the hippocampus (left) and the caudate (right). The curves were obtained from a nonparametric smoothing spline fit based on cross-sectional MR scans from 1100 healthy participants, published in Fjell et al. (2013). This general pattern of change was confirmed in the present longitudinal data.