First Application of the Standard Model of Diffusion to Subjective Cognitive Decline Reveals Novel Insights into White Matter Microstructure

Motivation: Subjective cognitive decline (SCD) is thought be a preclinical stage of Alzheimer's disease (AD). Prior SCD research has employed diffusion models that make assumptions about compartment diffusivities, assumptions which may be violated by pathology. The Standard Model Imaging (SMI) toolbox uses machine learning to estimate compartment diffusivities. Goal(s): To apply SMI to SCD for the first time, along with DKI and NODDI. Approach: 325 cognitively normal participants older than 55 were included. Participants were considered SCD if they endorsed problems with their memory. Results: Increased SMI perpendicular extracellular diffusivity in SCD overlapped with increased radial diffusivity, increased mean diffusivity, and decreased fractional anisotropy. Impact: Our findings suggest the Standard Model Imaging (SMI) can detect pathological changes in compartment diffusivities assumed to be indistinguishable or stable in other popular diffusion models. These findings are consistent with demyelination. Further research on demyelination in SCD is needed.