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Abnormally increased brain iron accumulation in deep gray matter is a common finding in Alzheimer’s disease (AD) and due to its paramagnetic nature, iron is changing the magnetic susceptibility of brain tissue. Recent validation studies showed that brain iron can be measured precisely by the novel MRI technique quantitative susceptibility mapping (QSM) in vivo, thus, enabling reliable and precise longitudinal investigations. Furthermore, QSM was more sensitive to disease-induced changes in Parkinson’s disease and multiple sclerosis than conventional MRI techniques. We hypothesize that pathologic brain iron accumulation can be assessed with higher sensitivity with QSM than with current MRI techniques such as R2* mapping and that regional QSM is a predictor for cognitive decline and disability.

We propose an explorative longitudinal study including patients with AD and age-matched control subjects which will be recruited for their 2 years follow-ups from our outpatient department and undergo extensive cognitive testing and quantitative 3 Tesla MRI. Regional differences of susceptibility and R2* in deep gray matter and the neocortex will be evaluated in AD patients and controls and related to the patients´ cognitive status at baseline. Follow-up MRI and clinical data with multivariate regression analysis serve to investigate the dynamics of AD-related changes of susceptibility, and their relation to cognitive functioning.

With this explorative longitudinal study in a large patient cohort we aim to clarify whether regional iron deposition is a cause or merely epiphenomenon of AD and if changes of magnetic susceptibility can serve as a predictive marker for AD progression.

This research is funded by the Austrian Science Fund FWF.

 

References

** Langkammer, C; Ropele, S; Pirpamer, L; Fazekas, F; Schmidt, R
MRI for iron mapping in Alzheimer's disease.
Neurodegener Dis. 2014; 13(2-3):189-1919

** Langkammer, C; Bredies, K; Poser, BA; Barth, M; Reishofer, G; Fan, AP; Bilgic, B; Fazekas, F; Mainero; C; Ropele, S
Fast Quantitative Susceptibility Mapping using 3D EPI and Total Generalized Variation.
Neuroimage. 2015 Feb 27. PubMed 

** Langkammer, C; Krebs, N; Goessler, W; Scheurer, E; Yen, K; Fazekas, F; Ropele, S
Susceptibility induced gray-white matter MRI contrast in the human brain.
Neuroimage. 2012; 59(2):1413-1419

** Langkammer, C; Schweser, F; Krebs, N; Deistung, A; Goessler, W; Scheurer, E; Sommer, K; Reishofer, G; Yen, K; Fazekas, F; Ropele, S; Reichenbach, JR
Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A post mortem validation study.
Neuroimage. 2012; 62(3):1593-1599