IronAge

PI: Grégoria Kalpouzos, gregoria.kalpouzos@ki.se

Advances in Magnetic Resonance Imaging (MRI) have made it possible to noninvasively quantify iron that accumulates in people’s brains. In the brain, iron is found in two forms: heme iron, found in the blood, and intra-cellular nonheme iron. Nonheme iron is a fundamental element that contributes to cellular metabolism. However, an overload of free nonheme iron in the brain is highly toxic, inducing oxidative stress, inflammation, cellular degradation, and cell death. Excessive concentrations of brain iron have been found in disorders such as Parkinson’s disease and Alzheimer’s disease and also in non-pathological aging. A high concentration of brain iron may lead to brain atrophy and motor and cognitive (e.g., memory) decline. However, no study has yet evaluated the impact of brain iron concentration on brain activity and other characteristics of the brain, such as molecular changes.

The aim of IronAge is to seek associations between age-related iron concentration, brain activity during the performance of tasks, and other brain characteristics. In a pilot study that included ca. 45 participants, we found that more brain iron was related to lower brain activity*. The ongoing longitudinal study aims to include up to 250 individuals aged 20-80 years. In addition to conducting MRI scans, we are taking blood samples to measure iron components and performing genetic studies after DNA extraction (to study the effects of iron genes). We are also collecting information about lifestyle, including nutrition.

Changes in brain iron concentration may constitute a biological marker for age-related cognitive decline and, possibly, development of neurodegenerative diseases.

The project is funded by a grant from the Swedish Research Council.

 

Publications:

Garzón B, Sitnikov R, Bäckman L, Kalpouzos G (2017). Automated segmentation of midbrain structures with high iron content. NeuroImage, in press. DOI: 10.1016/j.neuroimage.2017.06.016

Garzón B, Sitnikov R, Bäckman L, Kalpouzos G (2017). Can transverse relaxation rates in deep gray matter be approximated from functional and T2-weighted FLAIR scans for relative brain iron quantification? Magnetic Resonance Imaging 40: 75-82.

*Kalpouzos G, Garzón B, Sitnikov R, Heiland C, Salami A, Persson J, Bäckman L (2017). Higher striatal iron concentration is linked to frontostriatal underactivation and poorer memory in normal aging. Cerebral Cortex 27(6): 3427-3436.