Higher iron levels in the older adult brain are linked to higher R2 in gray matter and more white matter hyperintensities

Motivation: High iron levels in the brain of older adults have been linked to age-related neuropathologies and cognitive impairment. It is not yet known how iron levels relate to brain MRI characteristics above and beyond the effects of neuropathologies. Goal(s): To investigate the association of brain iron levels with R2 and white matter hyperintensities (WMH) independent of the effects of age-related neuropathologies in community-based older adults. Approach: Ex-vivo MRI, detailed neuropathologic evaluation, and inductively coupled plasma mass spectrometry were combined in 437 community-based older adults. Results: Higher iron levels are independently associated with higher R2 and WMH levels controlling for other metals and neuropathologies. Impact: We demonstrated that brain iron levels in older adults are associated with higher R2 and WMH independent of age-related neuropathologies and other metals, suggesting the presence of additional mechanisms of iron accumulation.