Population & Clinical Neuroepidemiology

Dr. Dr. Ahmad Aziz

Areas of investigation/research focus

Using deep (endo)phenotypic data obtained in the context of both population-based and clinical cohort studies, we aim to identify the risk factors, causes as well as trait and state markers of neurodegenerative diseases through application of epidemiological and bio-informatics approaches. Currently, the focus of my group is on the following three projects:

Tandem repeat variations as modifiers of brain structure and function.

Until recently it was assumed that genomic tandem repeat variations are only relevant for human health when mutated into extremely large expansions, causing several hereditary neurodegenerative diseases like Huntington disease and several spinocerebellar ataxias. However, we recently found that 1) polyglutamine disease-associated alleles with intermediate or pathological range cytosine-adenine-guanine (CAG) repeat lengths are much more prevalent in the general population than previously thought, 2) even CAG repeat variations in the normal range can act as modifiers of cognitive function, depression risk and body weight in the general population, and 3) in patients with neurodegenerative conditions like Huntington disease, Parkinson disease and Alzheimer disease, DNA repeat variations can modify disease characteristics such as age-of-onset and severity of symptoms. To identify novel genetic risk factors and causal mechanisms involved in the pathogenesis of neurodegenerative diseases, currently we are investigating the relation between a large number of tandem repeat-containing genomic loci and detailed (MR imaging-based) measures of brain structure, connectivity and function in the general population.

Elucidation of the neuroanatomical basis of motor function across lifespan.

Deterioration of motor function is an early feature of many neurodegenerative diseases, whereas physical activity may protect against neurodegeneration and cognitive decline. Elucidating the neuroanatomical basis of motor dysfunction across lifespan is thus crucial for both identification of early markers of, and development of more effective preventive and therapeutic strategies against, neurodegenerative diseases. Therefore, here we aim to assess the relation between accelerometer-based physical activity, as well as inertial motion sensor-based whole-body motor performance, with structural integrity and connectivity of relevant brain regions across lifespan in the population-based Rhineland Study.

Hypothalamic dysfunction as a driver of age-related cognitive decline.

The hypothalamus is the body’s principal homeostatic center and plays a crucial role in the modulation of cognition. However, whether hypothalamic pathology could be a risk factor for or marker of cognitive decline has not been studied in the general population for lack of a scalable high-throughput analysis method. Therefore, in this project we are developing a novel automated parcellation procedure to accurately delineate hypothalamic structures on MR images, and aiming to apply this method to relate various measures of hypothalamic structural and functional integrity to cognitive function in the population-based Rhineland Study.

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