Memory function declines with age. Some part of this is the result of outright structural damage in the brain, caused by the periodic rupture of small blood vessels that kills a small volume of tissue – a form of damage that proceeds that much more rapidly in hypertensive individuals, for all of the obvious reasons. But this is far from the only form of structural change in the brain. More subtle processes of damage and adaptation to damage also take place. Researchers here assess what can be done with modern tools in order to correlate structural change with cognitive decline.

Aging, even in the absence of clear pathology of dementia, is associated with cognitive decline. Neuroimaging, especially diffusion-weighted imaging, has been highly valuable in understanding some of these changes in live humans, non-invasively. Traditional tensor techniques have revealed that the integrity of the fornix and other white matter tracts significantly deteriorates with age, and that this deterioration is highly correlated with worsening cognitive performance. However, traditional tensor techniques are still not specific enough to indict explicit microstructural features that may be responsible for age-related cognitive decline and cannot be used to effectively study gray matter properties.

Here, we sought to determine whether recent advances in diffusion-weighted imaging, including Neurite Orientation Dispersion and Density Imaging (NODDI) and Constrained Spherical Deconvolution, would provide more sensitive measures of age-related changes in the microstructure of the medial temporal lobe. We evaluated these measures in a group of young (ages 20-38 years old) and older (ages 59-84 years old) adults and assessed their relationships with performance on tests of cognition.

We found that the fiber density (FD) of the fornix and the neurite density index (NDI) of the fornix, hippocampal subfields, and parahippocampal cortex, varied as a function of age in a cross-sectional cohort. Moreover, in the fornix and hippocampal subields DG/CA3 and CA1, these changes correlated with memory performance, even after regressing out the effect of age, suggesting that they were capturing neurobiological properties directly related to performance in this task.

These measures provide more details regarding age-related neurobiological properties. For example, a change in fiber density could mean a reduction in axonal packing density or myelination, and the increase in NDI observed might be explained by changes in dendritic complexity or even sprouting. These results provide a far more comprehensive view than previously determined on the possible system-wide processes that may be occurring because of healthy aging and demonstrate that advanced diffusion-weighted imaging is evolving into a powerful tool to study more than just white matter properties.