Imaging Alzheimer's genetic risk using diffusion MRI: A systematic review

Abstract

Diffusion magnetic resonance imaging (dMRI) is an imaging technique which probes the random motion of water molecules in tissues and has been widely applied to investigate changes in white matter microstructure in Alzheimer's Disease. This paper aims to systematically review studies that examined the effect of Alzheimer's risk genes on white matter microstructure. We assimilated findings from 37 studies and reviewed their diffusion pre-processing and analysis methods. Most studies estimate the diffusion tensor (DT) and compare derived quantitative measures such as fractional anisotropy and mean diffusivity between groups. Those with increased AD genetic risk are associated with reduced anisotropy and increased diffusivity across the brain, most notably the temporal and frontal lobes, cingulum and corpus callosum. Structural abnormalities are most evident amongst those with established Alzheimer's Disease. Recent studies employ signal representations and analysis frameworks beyond DT MRI but show that dMRI overall lacks specificity to disease pathology. However, as the field advances, these techniques may prove useful in pre-symptomatic diagnosis or staging of Alzheimer's disease.

Keywords: Alzheimer's Disease; Apolipoproteins E; Diffusion Tensor Imaging; Magnetic Resonance Imaging; Multifactorial Inheritance; Presenilin-1; Presenilin-2.

Fig. 1

PRISMA flow chart.

Fig. 2

The change in the diffusion signal (isotropic to anisotropic diffusion) can result from multiple different pathologies. States that can produce the same signal change include axonal loss, demyelination, axonal growth or edema.