Functional and microstructural MRI substrates of conserved memory in healthy ageing

The brain parenchyma undergoes several structural changes throughout life that significantly impact on its physiology, and are reflected in changes in cognitive abilities. The aim of this healthy ageing study was to investigate how age-related microstructural alterations affect the degree of preserved cognition in the elderly. We sought to identify brain region- and age-specific patterns that contribute to the physiological decline in cognition. To this end, we compared behavioral and microstructural MRI biomarkers in adult (6 months) and old (1.5 years) Wistar rats. Additionally, we analyzed fMRI resting state data to determine functional connectivity (FC) (n=22, 9 old), and diffusion weighted MRI to measure mean diffusivity (MD) (n=10, 5 old). Behavioral experiments in the Morris Water Maze were performed to measure short- and long-term memory. Our results revealed age-related changes in FC in important regions for memory and motor functions, including the cingulate/prelimbic and motor resting-state networks. MD was decreased in older animals compared to adults in most grey matter areas. No significant differences were found in short- or long-term memory across groups in MWM. However, there was a significant negative correlation between MD and latency in finding the platform, indicating a significant association between microstructural integrity and long-term memory. Overall, these results suggest that brain microstructure plays a prominent role in determining the degree of conserved abilities in the elderly, and holds therefore great potential as a platform to test interventions to promote healthy ageing.