ABSTRACT
RATIONALE Although the incidence of dementia increases exponentially with age, some individuals reach >100 years with fully retained cognitive abilities. To identify the characteristics associated with the escape or delay of cognitive decline, we initiated the 100-plus Study (www.100plus.nl).
DESIGN The 100-plus Study is an on-going prospective cohort study of Dutch centenarians who self-reported to be cognitively healthy, their first-degree family members and their respective partners. We collect demographics, life history, medical history, genealogy, neuropsychological data and blood samples. Centenarians are followed annually until death. PET-MRI scans and feces donation are optional. Almost 30% of the centenarians agreed to post-mortem brain donation.
COHORT DESCRIPTION To date (September 2018), 332 centenarians were included in the study. We analyzed demographic statistics of the first 300 centenarians (25% males) included in the cohort. Centenarians came from higher socio-economic classes and had higher levels of education compared to their birth cohort; alcohol consumption of centenarians was similar, and most males smoked during their lifetime. At baseline, the centenarians had a median MMSE score of 25 points (IQR: 22.0-27.5); the large majority lived independently, retained hearing and vision abilities and was independently mobile. Mortality was associated with cognitive functioning: centenarians with a baseline MMSE score ≥26 and <26 points had a mortality percentage of respectively 17% and 42% per annual year in the second year after baseline (p=0.003). The cohort was 2.1-fold enriched with the neuroprotective APOE-ε2 allele relative to 60-80 year-old population controls (p=4.8×10-7), APOE-ε3 was unchanged and the APOE-ε4 allele was 2.3-fold depleted (p=6.3×10-7).
CONCLUSIONS Comprehensive characterization of the 100-plus cohort of cognitively healthy centenarians might reveal protective factors that explain the physiology of long-term preserved cognitive health.
AUTHORS’ CONTRIBUTIONS
HH conceived and designed the study and wrote the manuscript; NB helped obtain ethical approval for the study and with the management of communication with participants and their proxies; TD is dedicated GP and analyzed GP reports, KP, EW, KS, LT, DB and SR visited the centenarians and helped design/improve the study as it evolved; SS advised on the design of the neuropsychological testing battery; FvP provided expert knowledge on occupation classification and the demographics of the 1910-1920 birth cohorts, HMH contributed substantive support for study set-up; MH helped with the study design and manages the Open Clinica database for data storage; PS contributed substantive support for the study and aided with obtaining necessary funding. All authors read and approved the final manuscript.
ACKNOWLEDGEMENTS
We are grateful for the collaborative efforts of all participating centenarians and their family members and/or relations. We also want to acknowledge the many people who contributed and continue to contribute to the study. The students involved in recruiting and visiting the centenarians: Lieke Jansma, Lieve Steins Bisschop, Sanne Koole, Sanne Hofman, Anna Kamsteeg, Saiedah Wekker, Matteo Neumann, and Marlous Jansen. The personnel who facilitated data collection and storage in available biobanks: Michiel Kooreman, Annemieke Rozemuller, Jeroen Hoozemans, Hans Gille, Charlotte Teunissen. The persons who advised on the collection procedures of specific data: Quinten Waisfisz, Eus van Someren, Ted Koene, Bart van Berckel, Wiesje van der Flier, Vivi Heine, Erik Sistermans, Cornelia van Duijn. We thank Marcel Reinders and Sven van der Lee for critically reviewing the manuscript before submission.
Footnotes
FUNDING: This work was supported by Stichting Alzheimer Nederland (WE09.2014-03), Stichting Diorapthe (VSM 14 04 14 02) and Stichting VUmc Fonds.