Cognition and brain iron deposition in whole grey matter regions and hippocampal subfields

Regional brain iron accumulation is observed in many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, and is associated with cognitive decline. We explored associations between age, cognition and iron content in grey matter regions and hippocampal subfields in 380 participants of the Aberdeen children of the 1950s cohort and their first-generation relatives (aged 26-72 years). Participants underwent cognitive assessment at the time of MRI scanning. Quantitative susceptibility mapping of these MRI data was used to assess iron content in grey matter regions and in hippocampal subfields. Principle component analysis was performed on cognitive test scores to create a general cognition score. Spline analysis was used with the Akaike information criterion to determine if order 1, 2 or 3 natural splines were optimal for assessing non-linear relationships between regional iron and age. Multivariate linear models were used to assess associations between regional iron and cognition. Higher iron correlated with older age in the left putamen across all ages and in the right putamen of only participants over 58. Whereas a decrease in iron with older age was observed in the right thalamus and left pallidum across all ages. Right amygdala iron levels were associated with poorer general cognition scores and poorer immediate recall scores. Iron was not associated with any measures of cognitive performance in other regions of interest. Our results suggest that, whilst iron in some regions was associated with cognitive performance, there is an overall lack of association between regional iron content and cognitive ability in cognitively healthy individuals.