Negative correlation between grey matter in the hippocampus and caudate nucleus in healthy aging.

Neurobiological changes that occur with aging include a reduction in function and volume of the hippocampus. These changes were associated with corresponding memory deficits in navigation tasks. However, navigation can involve different strategies that are dependent on the hippocampus and caudate nucleus. The proportion of people using hippocampus-dependent spatial strategies decreases across the lifespan. As such, the decrease in spatial strategies, and corresponding increase in caudate nucleus-dependent response strategies with age, may play a role in the observed neurobiological changes in the hippocampus. Furthermore, we previously showed a negative correlation between grey matter in the hippocampus and caudate nucleus/striatum in mice, young adults, and in individuals diagnosed with Alzheimer's disease. As such, we hypothesized that this negative relationship between the two structures would be present during normal aging. The aim of the current study was to investigate this gap in the literature by studying the relationship between grey matter in the hippocampus and caudate nucleus of the striatum, in relation to each other and to navigation strategies, during healthy aging. Healthy older adults (N = 39) were tested on the Concurrent Spatial Discrimination Learning Task (CSDLT), a virtual radial task that dissociates between spatial and response strategies. A regression of strategies against structural MRIs showed for the first time in older adults that the response strategy was associated with higher amounts of grey matter in the caudate nucleus. As expected, the spatial strategy correlated with grey matter in the hippocampus, which was negatively correlated with grey matter in the caudate nucleus. Interestingly, a sex difference emerged showing that among older adult response learners, women have the least amount of grey matter in the hippocampus, which is a known risk for Alzheimer's disease. This difference was absent among spatial learners. These results are discussed in the context of the putative protective role of spatial memory against grey matter loss in the hippocampus, especially in women.