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

Abstract

Although the incidence of dementia increases exponentially with age, some individuals reach more than 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). 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. 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); most centenarians lived independently, retained hearing and vision abilities and were independently mobile. Mortality was associated with cognitive functioning: centenarians with a baseline MMSE score ≥ 26 points had a mortality percentage of 17% per annual year in the second year after baseline, while centenarians with a baseline MMSE score < 26 points had a mortality of 42% per annual year (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). 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.Electronic supplementary materialThe online version of this article (10.1007/s10654-018-0451-3) contains supplementary material, which is available to authorized users.

Longitudinal Maintenance of Cognitive Health in Centenarians in the 100-plus Study

“…We genotyped or imputed apolipoprotein E (APOE) genotypes using standard procedures as previously described. 23 Carrying 1 or 2 alleles of APOE-ε4 was considered a risk-increasing factor associated with cognitive decline (APOE-ε3ε4, APOE-ε2ε4, or APOE-ε4ε4), whereas carrying 1 or 2 alleles of APOE-ε2 (APOE-ε2ε2 or APOE-ε2ε3) was considered a protective factor against cognitive decline (note that the APOE-ε2ε4 genotype was considered a risk-increasing factor). [27][28][29][30]…”

“…We classified hearing and vision capacities as good to moderate and as poor to very poor on the basis of the self-report of the centenarians and their family members and on the observations of the researcher during home visits. 23,32 History of heart disease, stroke and/or transient ischemic attack, diabetes, and hypertension was based on the medical report from the centenarian's general practitioner (GP) or, if not available, the self-report of the centenarians and/or a proxy. We determined medication use by the total number of prescription medication categories used by the centenarians according to the medication lists provided by their GPs (eg, cardiac medication, diuretics, anticoagulants, laxatives, antacids, analgesic, sedatives, antidiabetics, antidepressants, iron supplements, and others).…”

“…Indeed, age-associated diseases, including cardiovascular conditions, were previously found to be prevalent in our cohort. 23 When considering cardiovascular diseases as a risk factor associated with cognitive decline, this offers an opportunity to identify whether centenarians who maintain good cognitive health are resilient against such risk factors by comparing their cardiovascular disease prevalence with the prevalence of the centenarians with a lower and/or declining cognitive performance. 40,41 We found that the centenarians who maintained high levels of cognitive functioning did not have a lower prevalence of these diseases compared with all other centenarians in the cohort, which suggests that the escape of cognitive decline occurs irrespective of the effects of cardiovascular diseases.…”

Centanarians of Moscow: functional, cognitive and emotional state

“…По данным Нью-Йоркского регистра [21] средний уровень по шкале MMSE у супердолгожителей (возраст включения 95 лет) был 16.45, что примерно на 5 баллов ниже, чем результаты данного анализа. С другой стороны, данные исследования, проведенного в Нидерландах, продемонстрировали более высокий средний балл по шкале MMSE (23.9) [24]. В целом все работы подтверждают, что очень пожилые люди необязательно характеризуются когнитивными нарушениями [18][19][20][21].…”

Immune response and endocytosis pathways are associated with the resilience against Alzheimer’s Disease

“…[3] Yet, a small proportion of the population (<0.1%) escapes the disease, reaching at least 100 years while maintaining a high level of cognitive health. [4] Both the development and the escape from AD are determined by a combination of beneficial and harmful environmental and genetic factors that is unique for each individual. [1,5,6] Thus far, large collaborative genome-wide association studies (GWAS) have discovered common genetic variants associated with a small modification of the risk of AD.…”