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2019 Alzheimer's Association Research Grant (AARG)

Hypothalamic dysfunction as a driver of age-related cognitive decline

How do changes in a certain brain region lead to cognitive impairment in people with Alzheimer’s disease?

Ahmad Aziz, M.D., Ph.D.
German Center for Neurodegenerative Diseases
Bonn, Germany


In Alzheimer’s disease, one of the earliest changes in the brain is a loss of nerve cells in a region called the hypothalamus. The hypothalamus regulates several important body functions—hormone secretion, sleep, and appetite—that can impact cognitive function. But it is not clear how changes in the hypothalamus lead to thinking and memory problems in people with Alzheimer’s disease.  Dr. Ahmad Aziz proposes to investigate the relation between changes associated with the hypothalamus and decline in cognitive function in Alzheimer’s disease.

Research Plan

Dr. Ahmad Aziz and his multidisciplinary team will develop a new automated way to precisely analyze highly detailed brain scans of the hypothalamus, using Magnetic Resonance Imaging (MRI). Dr. Aziz will use this new method to examine brain scans from a group of more than 2000 people as part of the Rhineland study based in Germany. This study has been recently established to identify risk factors for neurodegenerative diseases including Alzheimer’s disease. Dr. Aziz plans to characterize the different structures present in hypothalamus, quantify the volumes of the regions in hypothalamus and investigate connections between the hypothalamus and other brain regions. The researchers will then apply their new method to associate specific changes observed in the hypothalamus and its connectivity to other brain regions to cognitive function. Lastly, Dr. Aziz and colleagues also plan to use advanced statistical techniques to identify which biological pathways are influenced by changes in hypothalamus—such as changes in appetite, sleep, hormone secretion etc. — and how this in turn impacts cognitive abilities.   


The study results may help in the understanding of changes in the hypothalamus that occur as people age and its impact in cognitive function as well as non-cognitive changes such as sleep, appetite etc. If successful, the results could help justify further exploration into hypothalamus as a brain region impacted in Alzheimer’s disease.

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