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

Brain Struct Funct. 2025 Apr 23;230(4):53. doi: 10.1007/s00429-025-02908-6.

ABSTRACT

Age-related hippocampal alterations often accompany cognitive decline, a significant risk factor for dementias. Modifiable lifestyle factors may help preserve hippocampal neural tissue and slow neurodegeneration and potentially promote cognition in old age. Here, we sought to identify the relationship between lifestyle and cognition in the context of the hippocampal microstructure across the lifespan. We used data from 494 subjects (36-100 years old) without cognitive impairment from the Human Connectome Project-Ageing study. We estimated hippocampal microstructure using myelin-sensitive (T1w/T2w ratio), inflammation-sensitive (MD) and fibre-sensitive (FA) MRI markers. We identified microstructural-lifestyle/-cognition using non-negative matrix factorization to integrate MRI measures into a multivariate spatial signature of hippocampal microstructure covariance followed by 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 are negatively associated with age, and 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 insulin levels and this is negatively associated with age in the presence of cardiovascular risk factors like high body mass index, blood pressure, triglycerides and blood glucose that are in turn associated with hippocampal neurodegeneration. Taken together, our results suggest that 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.

PMID:40266346 | DOI:10.1007/s00429-025-02908-6