Quantitative Susceptibility Mapping of Brain Iron in Healthy Aging and Cognition

Quantitative susceptibility mapping (QSM) is a magnetic resonance imaging (MRI) technique that can assess the magnetic properties of cerebral iron in vivo. Although brain iron is necessary for basic neurobiological functions, excess iron content disrupts homeostasis, leads to oxidative stress, and ultimately contributes to neurodegenerative disease. However, some degree of elevated brain iron is present even among healthy older adults. To better understand the topographical pattern of iron accumulation and its relation to cognitive aging, we conducted a systematic review of 47 QSM studies of healthy aging, with a focus on five distinct themes. The first two themes focused on age-related increases in iron accumulation in deep gray matter nuclei versus the cortex. The overall level of iron is higher in deep gray matter nuclei than in cortical regions. Deep gray matter nuclei vary with regard to age-related effects, which are most prominent in the putamen, and age-related deposition of iron is also observed in frontal, temporal, and parietal cortical regions during healthy aging. The third theme focused on the behavioral relevance of iron content and indicated that higher iron in both deep gray matter and cortical regions was related to decline in fluid (speed-dependent) cognition. A handful of multimodal studies, reviewed in the fourth theme, suggest that iron interacts with imaging measures of brain function, white matter degradation, and the accumulation of neuropathologies. The final theme concerning modifiers of brain iron pointed to potential roles of cardiovascular, dietary, and genetic factors. Although QSM is a relatively recent tool for assessing cerebral iron accumulation, it has significant promise for contributing new insights into healthy neurocognitive aging.