Longitudinal susceptibility Mapping in Alzheimer´s Disease

Abnormally increased brain iron accumulation in deep gray matter is a common finding in Alzheimers 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 Parkinsons 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 50 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.