The 100-plus Study
We are very grateful for all the centenarians and their families who participated in our study.
The research team together with 52 centenarians at the 100-plus day 2016.
The main source of inspiration for our research is the extraordinary case of Hendrikje van Andel-Schipper, a Dutch woman who died at age 115 without any symptoms of cognitive decline. She proved that cognitive decline is not inevitable and it is possible for the human brain to remain healthy until extreme ages. Intriguingly, her mother died at 100 years, also with full cognitive functions. This shows that reaching extreme ages without cognitive decline has a substantial heritable component, such that the genomes of those who escape cognitive decline until extreme ages may hold elements that lead to the maintenance of cognitive health during the aging process. Therefore, next to the identification of factors that increase risk of AD, our group focuses on the identification of factors that protect against AD.
We have conceived and set up the 100-plus Study cohort of cognitively healthy centenarians. During home visits we inquire about life-history of the centenarians, their family history, medical history, and current health.We assess their performance on neuropsychological tests, measure blood pressure and grip strength and we collect a blood sampe, for blood testing and genetic analyses. Optional parts of the study are: a visit to the outpatient clinic for PET-MRI and/or PET-CT imaging, feces donation to investigate the gut microbiome, and the generation of iPS cells from peripheral blood. Furthermore, all participants are informed about the option of post-mortem brain donation in collaboration with the Netherlands Brain Bank. Approximately 30% of the centenarians agrees to this. During (half-)yearly follow-up visits, we evaluate changes in general well-being and in neuropsychological test performance. Next to the centenarians, we also include their first-degree family members and their partners.
Together, this allows us to generate molecular data from different biomaterials per centenarian, which is unique for the 100-plus Study. Having such data available allows us to generate molecular profiles across multiple levels of cellular regulation and integrate this with levels of cognitive performance, demographic phenotypes, immunological features, and neuropathological changes in the centenarian brain.
Thus far, we have found that the genetic profiles of those who have escaped cognitive decline until extreme ages are enriched with protective genetic factors and depleted with risk factors. We study the downstream effects of these protective genetic factors on the composition on aged blood an brain tissues, which we collect from the centenarians. Ultimately, we aim to learn from the centenarians how to age without the burden of cognitive decline. With our studies, we aim to contribute to the improvement of diagnostic procedures of neurodegenerative diseases and to the design of personalized medication that sustains the molecular constellation of a healthy brain during the aging process.
See this article for more information about the 100-plus Study.
Ongoing projects with 100-plus cohort biomaterials
Healthy aging is the equivalent of escaping or delaying harmful or fatal aging-related diseases. To identify molecular features that underlie the escape of neurodegenerative diseases, we compare the multi-level data derived from the 100-plus Study cohort with similar data derived from the normal population or from Alzheimer’s disease cases. To achieve this, we collaborate intensely with many Alzheimer’s disease researchers.
Proteomics
Collaboration with Prof. Guus Smit (VU), Prof. Marcel Reinders (TU Delft): To identify proteins that associate with maintaining cognitive health in the centenarians we have performed mass spectrometry on 220 brain tissues-samples with and without AD across an age continuum from 50 – 110 years. Using state of the art statistical models, we identified proteins that change with age, but do not associate with AD, and proteins that specifically associate with AD, regardless of age. See also the projects of Andrea Ganz and Meng Zhang.
Neuropathology
Collaboration with Dr. Jeroen Hoozemans, Prof. A. Rozemuller (VUmc). Brain tissues donated by the centenarians are thoroughly investigated for the abundance of well-known disease-associated pathologies and this is associated with the level of cognitive performance.
Immunology
Collaborating with Prof. Jacques van Dongen, Prof. Frank Staal, Prof. dr. Eline Slagboom and dr. ir Erik van den Akker at the LUMC we are investigating the differential immune system response in cognitively healthy centenarians relative to the normal population.
iPSC cell generation
Collaboration with Dr. Vivi Heine (VU/VUmc). We are generating induced pluripotent stem cells from centenarians (iPSCs), and we have derived several fibroblast cell lines from skin-biopsies taken during brain autopsies. These can be used for functional experiments to test the genetic constellation that encodes long-term brain health.
Blood-based Biomarkers project
In collaboration with Prof. dr. ir. Charlotte Teunissen we will measure plasma biomarkers in all participants from the 100-plus Study (i.e. centenarians, their children and their partners).