Abnormalities of the Fornix in Mild Cognitive Impairment are Related to Episodic Memory Loss

The fornix is a major efferent tract of the hippocampus, a structure critical for normal memory function. However, the role of structural degradation of the fornix in memory dysfunction in mild cognitive impairment (MCI) has remained unclear. We used diffusion tensor tractography to measure microstructural properties of the fornix and the corticospinal tract (CST), as a control tract, in 206 cognitively normal subjects, 76 amnestic MCI (aMCI) and 51 non-amnestic MCI (naMCI) subjects. Hippocampal volumes were measured using deformation-based morphometry. We found significant fractional anisotropy reductions in the left fornix and radial diffusivity (RD) increases in bilateral fornices in aMCI, but not in naMCI, compared with controls. No significant changes in the CST were found in aMCI subjects, but naMCI subjects showed significantly increased RD and axial diffusivity of the right CST, compared with controls. Increased left fornical RD measure was correlated with poor verbal memory performance in aMCI subjects. In addition, reduced microstructural integrity of the fornix was associated with hippocampal atrophy in aMCI. This study suggests that microstructural alteration of the fornix is a contributor to early episodic memory dysfunction in non-demented individuals.