‘Resilience to cognitive decline to escape dementia: what we can learn from cognitively healthy centenarians’

Hosts: Esther Sammler and Dario Alessi 

Venue: MSI, Small Lecture Theatre, SLS

Abstract: 

A Dutch woman who died at age 115 without any symptoms of cognitive decline proved that cognitive decline is not inevitable. The question is: how can cognitive health be maintained during human aging? To learn about the molecular mechanisms underlying this extraordinary phenomenon, we set up the 100-plus Study, a longitudinal cohort study of cognitively healthy centenarians with the primary aim to identify protective genetic and biomolecular factors that associate with the escape of cognitive decline.  

Currently the cohort includes more than 450 centenarians from whom we collect various blood samples, DNA samples, and faeces samples, and ~30% of the centenarians agree to post mortem brain donation. Centenarians are visited at home and subjected to a life-history questionnaire, a comprehensive cognitive testing battery, and we collect medical history from their GPs. Furthermore, we collect blood-samples from the siblings and the children of the centenarians (~75 years old) and their respective partners.  

By comparing the biomaterials from these centenarians with those from Alzheimer Disease patients we identify both, protective and risk-increasing factors. Thus far we have shown that centenarians can have very high levels of cognitive performance, which are mostly maintained in the ensuing years after study inclusion. Centenarians can be resilient to very high levels of neuropathological substrates associated with neurodegenerative disease. We see that as a group, they are enriched with genetic variants that protect against Alzheimer’s Disease and depleted with risk-increasing genetic variants. In my talk I will present an overview of our findings in the 100-plus Study: covering our genetic, neuropathological, and brain proteomic, neuropsychological, and immunological findings. To learn more about the study please visit www.holstegelab.eu 

Bio: 

Henne Holstege heads the section of Genomics of Neurodegenerative Diseases and Aging at the Department of Human Genetics at the Amsterdam University Medical Center. Additionally, she is part of the staff of the Amsterdam Alzheimer Center. Holstege majored in biochemistry at the University of Leiden, after which moved to Harvard Medical School in Boston to study the neurochemistry associated with satiety. She went on to do her PhD at the Netherlands Cancer Institute where she studied the germline and somatic genetic aberrations associated with the development of breast cancer. Meanwhile she was intrigued by the finding that escaping aging related diseases often occurs within families. In 2010, Holstege moved to the Amsterdam UMC where built a new research section at the department of Human Genetics where she focuses on the identification of genetic and genomic factors associated with neurodegenerative diseases. Holstege won the Alzheimer Research Prize 2020 from the Hans und Ilse Breuer Foundation. For more information about her team and the projects: See www.holstegelab.eu.