Superficial white matter (SWM) contains short fibres and has largely been overlooked in Alzheimer’s disease (AD). Standard MRI approaches face confounding
effects of complex fibre organisation and proximity to the cortex when measuring
SWM in vivo. This thesis investigates SWM in AD by applying advanced MRI
techniques to overcome these limitations.
First, SWM in a cohort of young-onset AD and healthy controls was investigated using an advanced diffusion MRI model. Findings showed that young-onset
AD participants have lower density, but increased dispersion, of SWM neurites
compared to healthy controls. The second project found that these advanced diffusion MRI metrics are associated with independent quantitative MRI metrics sensitive to microstructure, and indicate previous findings are linked to losses in SWM
myelin and iron. Project three explored the confounding effect of nearby CSF on
cortical diffusion MRI measures and showed that a tissue-weighting approach can
ameliorate CSF’s influence on regional averages. Project four investigated whether
SWM is affected in autosomal dominant AD. Results supported earlier findings of
lower density and higher dispersion of SWM neurites in symptomatic mutation carriers compared to non-carriers. Presymptomatic mutation carriers also had a lower
density of neurites in entorhinal SWM. The final project used high-resolution 7T
MRI to limit the influence of partial volume effects from nearby tissues on SWM
measures in typical and atypical AD participants and healthy controls. An interim
analysis qualitatively supports a loss of myelin and iron, with a potential increase
in dispersion, occurring in the SWM during AD.
In summary, SWM undergoes both degenerative and organisational changes
during AD that coincide with a loss of iron. This extends the literature by overcoming limitations of standard MRI techniques previously used to investigate SWM in
AD. SWM represents an overlooked region of brain changes in AD that may help
detect and characterise the disease
