Identification of central noradrenergic mechanisms connecting and distinguishing older age depression and dementia in MRI

• Applicant: Dr. Thomas Liebe
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 565180459

Depression and dementia in older patients are clinically difficult to distinguish because their symptoms show significant overlap. A disruption in the neurotransmitter noradrenaline in the brain could play a crucial role in the genesis and manifestation of both conditions, explaining the similar symptoms in patients. Using a highly accurate method developed by our team, we can examine the neural connections and functionality of the locus coeruleus - a brainstem nucleus that controls nearly all noradrenaline release - via brain imaging in a magnetic resonance tomograph (MRI). Our preliminary studies show that this disruption in the noradrenaline system, present in both conditions, differs in detail between early stages of dementia and depression. Therefore, our goal is to use our MRI results to explain the clinical manifestation and differentiate between these two groups, which is crucial for timely and appropriate patient therapy. We will compare a group of healthy older adults, a group of older patients with depression, and a group of older patients at high risk for or with manifest early Alzheimer's dementia, as indicated by clinical signs and amyloid biomarkers, using MRI. First, we will depict the differences in the structure and functionality of the noradrenaline system at rest between the groups. Then, we will analyze the functionality of the noradrenaline system in both healthy individuals and patients while they perform tasks in the MRI scanner, to understand how the changes observed at rest affect behavior in dementia and depression, and to highlight the subtle differences between these conditions. The project will contribute to improving the diagnosis of both conditions and enhancing the understanding of the causes of depression and dementia.

• DFG Programme: Research Grants
• Co-Investigators: Professorin Dr. Kathrin Finke; Professor Dr. Martin Walter