Age- and memory- related differences in hippocampal gray matter integrity are better captured by NODDI compared to single-tensor diffusion imaging.

Single-tensor diffusion imaging (DTI) has traditionally been used to assess integrity of white matter. For example, we previously showed that integrity of limbic white matter tracts declines in healthy aging and relates to episodic memory performance. However, multi-compartment diffusion models may be more informative about microstructural properties of gray matter. The current study examined hippocampal gray matter integrity using both single-tensor and multi-compartment (neurite orientation dispersion and density imaging, NODDI) diffusion imaging. Younger (20-38 years) and older (59-84 years) adults also completed the Mnemonic Similarity Task to measure mnemonic discrimination performance. Results revealed age-related declines in both single-tensor (lower fractional anisotropy, higher mean diffusivity) and multi-compartment (higher restricted, hindered and free diffusion) measures of hippocampal gray matter integrity. As expected, NODDI measures (hindered and free diffusion) captured more age-related variance than DTI measures. Moreover, mnemonic discrimination of highly similar lure items in memory was related to hippocampal gray matter integrity in younger but not older adults. These findings support the notion that age-related differences in gray matter integrity are better captured by multi-compartment versus single-tensor diffusion models and show that the relationship between mnemonic discrimination and hippocampal gray matter integrity is moderated by age.