The 100-plus Study of cognitively healthy centenarians: rationale, design and cohort description

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.