ABSTRACT
BACKGROUND Although the prevalence 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).
METHODS The 100-plus Study is an on-going prospective cohort study of Dutch centenarians who self-reported to be cognitively healthy, and family members. 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 is optional. Almost 30% of the centenarians agreed to post-mortem brain donation.
RESULTS The first 300 centenarians (25% males) included in the cohort 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-rate of respectively 0.19 and 0.54 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 APOE-ε4 was 2.3-fold depleted (p=6.3×10−7).
CONCLUSIONS The 100-plus Study cohort represents cognitively healthy centenarians. Comprehensive characterization of this cohort might reveal protective factors that explain the pathophysiology of long-term preserved cognitive health.