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.
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.
Prof. Dr. med. Michael Kreißl
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).
Dr. Kathrin Baldauf
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.
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
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.
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
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
Plasma concentrations of anti-inflammatory cytokine TGF-β are associated with hippocampal structure related to explicit memory performance in older adults
M Raschick, A Richter, L Fischer, L Knopf, A Schult, R Yakupov, G Behnisch, K Guttek, E Düzel, I R Dunay, C I Seidenbecher, B Schraven, D Reinhold, B H Schott J Neural Transm (2023)
The relationship between resting-state amplitude fluctuations and memory-related deactivations of the default mode network in young and older adults
Jasmin M Kizilirmak, Joram Soch, Hartmut Schütze, Emrah Düzel, Hannah Feldhoff, Larissa Fischer, Lea Knopf, Anne Maass, Matthias Raschick, Annika Schult, Renat Yakupov, Anni Richter, Björn H Schott Hum Brain Mapp (2023)
Emrah Düzel, Gabriel Ziegler, David Berron, Anne Maass, Hartmut Schütze, Arturo Cardenas-Blanco, Wenzel Glanz, Coraline Metzger, Laura Dobisch, Martin Reuter, Annika Spottke, Frederic Brosseron, Klaus Fliessbach, Michael T Heneka, Christoph Laske, Oliver Peters, Josef Priller, Eike Jakob Spruth, Alfredo Ramirez,…
Ciampa CJ, Parent JH, Harrison TM, Fain RM, Betts MJ, Maass A, Winer JR, Baker SL, Janabi M, Furman DJ, D’Esposito M, Jagust WJ, Berry AS. Neuropsychopharmacology (2022)
Xenia Grande, David Berron, Anne Maass, Wilma A. Bainbridge, Emrah DüzelNeuropsychologia, Neuropsychologia (2021)
Hippocampal vascularization patterns exert local and distant effects on brain structure but not vascular pathology in old age
Niklas Vockert, Valentina Perosa, Gabriel Ziegler, Frank Schreiber, Anastasia Priester, Marco Spallazzi, Berta Garcia-Garcia, Merita Aruci, Hendrik Mattern, Aiden Haghikia, Emrah Düzel, Stefanie Schreiber, Anne Maass Brain Communications (2021)