Abstract
Background
Recent magnetic resonance imaging (MRI) studies have established that brain iron accumulation might accelerate cognitive decline in Alzheimer’s disease (AD) patients. Both normal aging and AD are associated with cerebral atrophy in specific regions. However, no studies have investigated aging- and AD-selective iron deposition-related cognitive changes during normal aging. Here, we applied quantitative susceptibility mapping (QSM) to detect iron levels in our cortical signature regions and assessed the relationships among iron, atrophy, and cognitive changes in older adults.
Methods
In this Taizhou Imaging Study, 770 older adults (mean age 62.0 ± 4.93 years, 57.5% women) underwent brain MRI to measure brain iron and atrophy, of whom 219 underwent neuropsychological tests nearly every 12 months for up to a mean follow-up of 2.68 years. Global cognition was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Domain-specific cognitive scores were obtained from MoCA subscore components. Regional analyses were performed for cortical regions and 3 signature regions: aging (AG)-specific regions, AG regions and AD signature meta-ROIs (Fig. 2). The QSM and cortical morphometry means of the above ROIs were also computed.
Results
Significant associations were found between QSM levels and cognitive scores. In particular, after adjusting for cortical thickness of regions of interest (ROIs), participants in the upper tertile of the cortical and AG-specific signature QSM exhibited worse global cognitive function than did those in the bottom tertile [Table 2; \(\beta\) = -0.104, p = 0.035; \(\beta\) = -0.118, p = 0.020, respectively]. Longitudinal analysis suggested that QSM values in all ROIs might predict cognitive decline in global cognition and key domains such as attention and visuospatial function (Table 3, Fig. 3; all p < 0.05). Furthermore, iron levels were negatively correlated with classic MRI markers of cortical atrophy (cortical thickness, gray matter volume, and local gyrification index) in total, AG-specific, and AG signature regions (Fig. 2; all p < 0.05).
Conclusion
AG- and AD-selective iron deposition was associated with atrophy and cognitive decline in elderly people, highlighting its potential as a neuroimaging marker for cognitive aging.