Characterization of white matter hyperintensities in Down syndrome

Area of Science:

• Neuroimaging
• Neurodegenerative Diseases
• Genetics

Background:

• White matter hyperintensities (WMHs) are common in Down syndrome (DS).
• Their specific location and links to Alzheimer's disease (AD) biomarkers are not well understood.
• This study investigates WMH topography in DS and its association with AD pathology.

Purpose of the Study:

• To explore the topographical distribution of WMHs in adults with DS.
• To examine the relationship between WMHs, sociodemographic factors, and Alzheimer's disease biomarkers.
• To understand the association of WMHs with gray matter volumes in DS.

Main Methods:

• 261 adults with DS and 131 euploid controls underwent MRI scans.
• WMHs were segmented in white matter layers and lobar regions.
• Associations with AD stages, demographics, CSF biomarkers, and gray matter volume were analyzed.

Main Results:

• WMHs appeared around age 43 in DS, increasing with age.
• WMH volume rose along the AD continuum, especially in periventricular and lobar regions.
• Significant associations were found between WMHs, CSF biomarkers, and temporo-parietal gray matter volume.

Conclusions:

• WMHs increase significantly 10 years prior to AD symptom onset in DS.
• WMHs are closely associated with AD biomarkers, including neurofilament light chain.
• These findings suggest WMHs are integral to AD pathophysiology in DS, independent of vascular factors.