Investigate differences in white matter (WM) integrity between Alzheimer’s and healthy subjects (HC) using diffusion tensor imaging (DTI) and free-water (FW)-DTI.

Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia in older adults. DTI has been used in AD to assess WM integrity with metrics such as fractional anisotropy (FA), axial/radial diffusivities (AxD and RD), and mode of anisotropy (MA). However, DTI is susceptible to the effects of extracellular FW, which can be removed using an advanced FW-DTI model. Here, we compared these two DTI techniques for assessing WM integrity in AD. 

MRI-data were download from the OASIS-3 database; 30 HCs and 28 AD patients were included. DTI data were preprocessed using FSL. The diffusion tensor for both methods was fit using an in-house MATLAB script. FSL-Randomise tool was used to compare WM between groups using ANCOVA, with age and gender as covariates.

With both standard and FW-DTI, decreased FA consistent with neurodegeneration was found in AD, mainly in the corpus callosum and fornix. Widespread nonspecific increases in AxD and RD were observed with standard DTI; in contrast, AxD and RD were largely decreased with FW-DTI. Using FW-DTI, improved consistency was observed in both the spatial location of altered DTI metrics and in terms of the magnitude and direction of these alterations. With both standard and FW-DTI, increased MA coupled with increased FA in AD was found in the anterior thalamic radiation and cortical spinal tract, suggestive of a loss of crossing fibers. Higher FW was observed in AD compared to HC in several WM areas, indicative of AD-associated neurodegeneration.

The implementation of a FW correction algorithm for DTI improves the accuracy of derived DTI metrics and better reflects the underlying pathology of AD. FW-DTI metrics may provide novel insight into AD-related WM changes.