Human molecular imaging ageing and SuperAgeing cohort

Z03

Episodic memory records and recalls our personal experiences. As we age, episodic memory declines but the amount of decline differs considerably between individuals. Early beginnings of Alzheimer’s disease places additional strains on episodic memory, long before signs of dementia are visible. Again, individuals considerably differ by how much they are affected. The goal of the Z03 project is to quantify the health and size of episodic memory regions in the brain using cutting edge and novel technologies. We seek to find out how people differ as they age and what sets “SuperAgers” apart from normal agers.

Principal Investigators

CRC 1436 Spokesperson Emrah Düzel

Prof. Dr. med. Emrah Düzel

CRC 1436 member Michael Kreißl

Prof. Dr. med. Michael Kreißl

CRC 1436 member Anne Maaß

Dr. Anne Maass

Prof. Dr. med. Emrah Düzel

Emrah Düzel has trained as a neurologist in Germany (in Bonn and Magdeburg). He is working as a cognitive neurologist on the functional anatomy of human episodic memory networks, neuromodulatory circuits, their clinical and mechanistic alterations in aging and neurodegeneration and their scope for plasticity. He leads the Institute of Cognitive Neurology and Dementia Research and Memory Clinic at the OvG University Magdeburg. As speaker of the Magdeburg site of the German Center for Neurodegenerative Diseases (DZNE, Helmholtz Society), he supports the implementation and analysis of imaging and cognition measures for early Alzheimer’s disease. He is also a part time group leader at the Institute of Cognitive Neuroscience at the Univ. College London, a fellow of the Max-Planck School of Cognition and co-founder of the digital health start-up neotiv. Within the newly founded German Network of Memory Clinics, he coordinates a working group on Digital Health and Telemedicine.

Institut:Otto von Guericke University Magdeburg, Medical Faculty

:German Center for Neurodegenerative Diseases, Magdeburg

Project Title:A04 Cognitive enhancement by the anti-ageing protein Klotho – from molecular mechanisms to interventions

:B02 Neural resources of mnemonic discrimination and their interaction with hidden pathology in older adults and SuperAgers

:Z03 Human molecular imaging ageing and SuperAgeing cohort

Prof. Dr. med. Michael Kreißl

coming soon

Institut:Otto von Guericke University Magdeburg, Medical Faculty

Project Title:Z03 Human molecular imaging ageing and SuperAgeing cohort

Dr. Anne Maass

Dr. Anne Maass is a group leader at the DZNE (since 2019) and her work focuses on the use of Multimodal neuroimaging techniques for understanding how brain function changes in aging and age-related disease, such as Alzheimer’s disease (AD). In her previous work, she used ultra-high resolution functional MRI to investigate memory pathways in the medial temporal lobe and its plasticity in the human brain in aging and disease. During her Post Doc at UC Berkeley, she combined functional MRI with molecular imaging (PET), which allows to assess AD pathology, to investigate how early tau and amyloid-beta pathology affects memory function, ultimately resulting in memory deficits. At the DZNE she now combines different neuroimaging techniques to better understand what drives the accumulation of age-related pathology (e.g. aberrant activation) and why some people do not develop pathology (are resistant) or why others remain cognitively normal in face of pathology (are resilient). Within the SFB1436 she leads the Z03 project together with Prof. Düzel and Prof. Kreissl as well as the project B04 together with Esther Kühn and Stefanie Schreiber (Co-PI: Nadine Diersch).

Institut:German Center for Neurodegenerative Diseases, Magdeburg

Project Title:B04 Effects of hippocampal vascularization patterns on the neural resources of MTL neurocognitive circuits

:Z03 Human molecular imaging ageing and SuperAgeing cohort

Co-Workers

picture is coming soon

Dr. Kathrin Baldauf

CRC 1436 member Larissa Fischer

Larissa Fischer

CRC 1436 member Anne Hochkeppler

Anne Hochkeppler

CRC 1436 member Eóin Molloy

Dr. Eóin Molloy

picture is coming soon

Dr. Peter Schulze

CRC 1436 member Beate Schumann-Werner

Beate Schumann-Werner

CRC 1436 member Svenja Schwarck

Svenja Schwarck

Dr. Kathrin Baldauf

coming soon

Larissa Fischer

Larissa Fischer is a research assistant in the Z03 project. She will receive her Master’s degree in psychology with a focus on cognitive neuroscience at the end of 2022. She studied at Otto von Guericke University in Magdeburg and spent a semester abroad at the University of Cambridge. She is interested in learning and memory processes and how they change with age.

Anne Hochkeppler

coming soon

Dr. Eóin Molloy

Eóin is a postdoctoral researcher at the University Clinic for Radiology and Nuclear Medicine, OvGU and the Multimodal Neuroimaging (MuMoNi) Lab at the DZNE, Magdeburg. Eóin completed his PhD at the MPI for Human Cognitive & Brain Sciences in Leipzig. His research interests include characterizing the molecular and functional mechanisms of pathological ageing and dementia with an emphasis on the treatment and prevention of Alzheimer’s disease. Within the SFB, Eóin’s projects include the Z03 project, which is focused on delineating the neural resources of SuperAgers, with a goal towards understanding how these older individuals remain cognitively healthy into later life.

Dr. Peter Schulze

coming soon

Beate Schumann-Werner

Beate Schumann-Werner is a speech-language pathologist. She completed her master’s degree at RWTH Aachen University. After a research visit at the Upper Airway Dysfunction Lab at the University of Florida/ Gainesville, she started her PhD at RWTH Aachen University. In her doctoral study, she focused on neural correlates for dysphagia in Huntington’s Disease. She previously worked as Research Assistant and coordinator of the Neuropsychological Therapy Ward at the University Hospital Aachen. Since July 2022, Beate is supporting project Z03 within the SFB as Research Assistant. Her clinical and research interests include diagnosis and treatment of swallowing and communication disorders associated with neurodegenerative diseases.

Svenja Schwarck

coming soon

What is a SuperAger?

SuperAgers are healthy adults aged at least 80 years old. Unlike “normal” agers, SuperAgers have preserved cognitive function in domains such as memory, with their abilities being more similar to that of adults aged 20 to 30 years younger. Many different neuropsychological tests can be used to identify a SuperAger. In our central project, we identify SuperAgers using several tests, one of which is called the Rey Auditory Verbal Learning Test (RAVLT) and the Rey-Osterrieth (ROCF) complex figure, a well-established test used to examine memory function. By scoring in the age range of adults aged 50 to 60 years, we can classify older people as SuperAgers.

What happens in the brains
of SuperAgers?

Tau is a protein found in the brain that plays a major role in stabilizing microtubules; cylindrical structures inside brain cells that form and maintain organization and function. In Alzheimer’s disease, tau protein becomes misfolded and clumps together to form neurofibrillary tangles which cause degradation and death of the cell. Though a hallmark of Alzheimer’s disease, tau also accumulates in the brains of cognitively healthy people and has been linked to cognitive ability. Tau early aggregates in the medial temporal lobe (MTL), a region important for memory function. How this tau accumulation might differ in SuperAgers is still not understood. One hypothesis, however, has been termed “brain resistance” and suggests that tau accumulation is reduced in SuperAgers, leaving them with intact memory performance in later life. Another possibility is referred to as “brain reserve” or “resilience” and suggests that SuperAger brains may be better able to withstand the effects of tau on memory in later life, possibly due to higher levels of education or other lifestyle factors. Understanding this mechanism is a central goal of the Z03 project.

How can we investigate tau in SuperAger brains?

Positron emission tomography (PET) is a well-established neuroimaging technique that capitalizes upon the physical properties of metabolic and neurochemical processes in the brain. Recently, novel methods have been developed to better image tau accumulation in the brain. For the Z03 project, we will collaborate with the Department of Nuclear Medicine at University Hospital Leipzig (led by Prof. Osama Sabri) to use a relatively new radiotracer known as 18F-PI-2620, which has been recently established in both Alzheimer’s patients and healthy adults, to quantify tau in brain regions. Compared to previous tau radiotracers, 18F-PI-2620 has been shown to exhibit less unspecific binding and a fast washout of non-target areas. With this method, we will be able to quantify the amount of tau in key brain regions of SuperAgers (such as the MTL) and compare these measures to age-matched controls.

The goals of our project

In a large sample of cognitively healthy older adults, we aim to characterize the molecular, functional, and structural characteristics of SuperAger brains as well as their cognitive and memory abilities. To do this, we will recruit 50 SuperAgers and 50 age matched “normal” agers. In addition, we will also recruit 300 further participants aged between 60 and 79 years. All participants will undergo a 3 Tesla MRI scan to assess brain structure, brain function and blood flow. A subsample of subjects will undergo MR-PET scans to measure regional tau accumulation. We will also assess other biological markers, including amyloid-beta from blood in cooperation with the DZNE Göttingen (Prof. Jens Wiltfang) and genetic factors (APOE4, BDNF, Klotho). We are interested in characterizing SuperAgers based on their cognition, genetics, brain function and structure, lifestyle factors, and fitness to investigate the factors that may contribute to SuperAger status. Similarly, we are interested in how these factors relate to memory in the other cognitively normal elderly. Furthermore, the Z03 project aims to put our participants into sub-groups for allocation to “sub-projects” – smaller projects with similar goals and interests. Establishing this healthy cohort will allow collaboration between different research groups and foster further investigation of healthy human ageing.

A Look into the future

A next step for the Z03 project following our SuperAger assessments will involve a follow-up in a subsample of older participants after several years, who will undergo a further MRI-PET scan and neuropsychological testing. More generally, by collaborating and sharing data with our colleagues, we will enable our fellow CRC projects to extend their research to questions related to brain resilience, reserve, maintenance and overall healthy ageing.

Publications of the project Z03