Magnetic resonance imaging biomarkers for cognitive decline in Down syndrome

Abstract Neuroimaging presents an opportunity to study Alzheimer's disease (AD) in Down syndrome (DS). Structural MRI studies have shown a pattern of neurodegeneration that mimics sporadic AD (e.g., hippocampal volume loss), as well as surprising evidence of cerebrovascular pathology despite limited vascular risk factors in DS. Diffusion MRI studies have also shown in people with DS a pattern of frontal white matter decline similar to sporadic AD, while resting state fMRI has implicated default mode network abnormalities associated with AD in people with DS, again mirroring findings in sporadic AD. Preliminary studies with arterial spin labeling suggest changes in blood flow in people with DS are associated with dementia status. Finally, magnetic resonance spectroscopy yields novel insights into metabolites that may be implicated in AD pathophysiology in DS. We suggest that longitudinal studies evaluating and benchmarking these techniques against more traditional biomarkers are critical to advancing our understanding of AD in DS.