Cognitive-and lifestyle-related microstructural variation in the ageing human hippocampus

Abstract

Ageing is a biological process associated with the natural degeneration of various regions of the brain. Alteration of neural tissue in the hippocampus with ageing typically results in cognitive decline that may serve as a risk factor for dementia and other neurodegenerative diseases. Modifiable lifestyle factors may help preserve hippocampal neural tissue (microstructure) and slow down neurodegeneration and thus promote healthy cognition in old age. In this study, we sought to identify potential modifiable lifestyle factors that may help preserve microstructure in the hippocampus. We used data from 494 subjects (36-100 years old) without clinical cognitive impairment from the Human Connectome Project-Aging study. We estimated hippocampal microstructure using myelin-sensitive (T1w/T2w ratio), inflammation-sensitive (MD) and fibre-sensitive (FA) MRI markers. Non-negative matrix factorization was used to integrate the signals of these images into a multivariate spatial signature of microstructure covariance across the hippocampus. The associations between hippocampal microstructural patterns and lifestyle factors & cognition were identified using partial least squares analysis. Our results reveal that the preservation of axon density and myelin in regions corresponding to subicular regions and CA1 to CA3 regions of the hippocampi of younger adults is associated with improved performance in executive function tasks, however, this is also associated with a decreased performance in memory tasks. We also show that microstructure is preserved across the hippocampus when there is normal hearing levels, physical fitness and normal insulin levels in younger adults of our study even in the presence of cardiovascular risk factors like high body mass index, blood pressure, triglycerides and blood glucose known to be associated with hippocampal neurodegeneration. This preservation is not observed in older adults when there are no normal levels of insulin, physical fitness and hearing. Taken together, our results suggest that certain lifestyle factors like normal hearing, physical fitness and normal insulin levels may help preserve hippocampal microstructure which may be useful in maintaining optimum performance on executive function tasks and potentially other modes of cognition.