Background
Methods/study design
Inclusion and exclusion criteria
Recruitment and research visits
Recruitment
Baseline visit
Study participants | Actions |
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Centenarians
|
First baseline visit: interview
|
Phase 1 and Phase 2 | Formalities for study inclusion: ICF; Proof of age |
Childhood living environment; Education; Marriage/Partners; Number of children, Religion, Occupation; Occupation of parents and partner | |
Genealogy of first degree family members and partners; Disease history in family | |
Lifestyle Questionnaire: Smoking habits; Drinking habits; Lifetime cognitive activity scale; situation during WWII | |
Disease history (self-report): weight/length; incontinence; medication intake, dental condition (stopped); hospital visits/anesthesia | |
Researcher subjective estimate of sight, hearing, mobility, cognitive status; | |
Centenarian presentation: current housing situation, total hours of care; ADL (Barthel index); sleep quality (PSQI); Geriatric Depression Scale (GDS); cognitive well-being judged by informant (IQ-CODE) | |
Collection of biomaterials and biomarkers: blood sampleab | |
Second baseline visit
| |
Neuropsychological test battery: Table 2 | |
Measurement of grip strengthb and blood pressureb | |
Follow up
| |
MMSE at last visit > 20: yearly visit: update of general well-being, disease history, and missed items at baseline interview; Researcher subjective estimate of sight, hearing, mobility, cognitive status; | |
Neuropsychological testing battery (Table 2) Barthel index; GDS; IQ-CODE, grip strength measurementb; blood pressure measurementb | |
MMSE at last visit ≤ 20; phone interview: update of general well-being, disease history, and missed items at baseline interview; IQ-CODE (by mail), ADL (Barthel index) | |
For brain donors: half yearly follow-up: TICs-M (by telephone); IQ-CODE (by mail) | |
GP
| |
At baseline inclusion: request for summary of medical events | |
Post mortem: request medical events leading to death | |
Optional in Phase-2
| |
MRI-PET or PET-CT scan | |
Feces donation | |
iPS cell generation | |
Post mortem brain donation | |
Centenarian children and partners Phase-2 |
Baseline visit
|
Formalities for study inclusion: ICF | |
Collection of blood sampleb | |
Mail: Questionnaire on lifestyle, general well-being, education and occupation, disease history and genealogy | |
Follow up
| |
No follow-up | |
GP
| |
For specific cases: request for summary of medical events | |
Centenarian-siblings and partners, centenarian-partners Phase-2 |
Baseline visit
|
Update lifestyle questionnaire, current health, disease history and general well-being Blood sample, MMSE, Barthel index; IQ-CODE; grip strengthb and blood pressure measurement,b estimation of sight, hearing, and mobility; | |
Researcher subjective estimate of sight, hearing, mobility, cognitive status; | |
Mail: questionnaire on lifestyle, general well-being, education and occupation, disease history, and genealogy | |
Follow up
| |
Yearly: TICs-M (by telephone); IQ-CODE (by mail) | |
GP
| |
For specific cases: request for summary of medical events |
Domain or goal | Assessment/questionnaires | Duration (min) |
---|---|---|
Cognitive functioning
| ||
Overall cognitive functioning | Researcher subjective impression of cognitive health (see “Methods”) | 0 |
5 | ||
3 | ||
Telephone Interview Cognitive Status—Modified (TICS-M)d [90] | ||
Memory | CERAD 10-word list—immediate and delayed recall [91] | 15 |
Visual Association Test—Memory [92] | 5 | |
6 | ||
Attention | 3 | |
NA | ||
Executive functions | 3 | |
2 | ||
3 | ||
3 | ||
10 | ||
Amsterdam Dementia Screening Test—Meander figure [107] | 2 | |
Language | 2 | |
Visual Association Test—Naming [92] | 1 | |
Visuo-spatial functioning/construction | 3 | |
2 | ||
Visual Object and Space Perception (VOSP) Batteryb—subtest Number Location [113] | 3 | |
Depression, ADL, sleep, lifestyle, geriatric impairments
| ||
Depressive symptoms | Geriatric Depression Scale-15 (GDS) [29] | 4 |
(Instrumental) Activities of daily living | 3 | |
3 | ||
Lifetime cognitively stimulating experience | 5 | |
Sleep quality | Pittsburgh Sleep Quality Indexa (PSQI) [28] | 5 |
Geriatric impairments | Researcher subjective impression of sight, hearing, mobility (“Methods”) | 0 |
Follow-up visits
Data collection
Centenarian presentation
Vision | Hearing | Mobility | |
---|---|---|---|
Good | Able to read newspapers and watch television | Able to have and follow a conversation in a group of people | Able to walk independently (with or without help of a walking stick or walker) |
Moderate | Able to read large texts with large letters and watch television | Able to have a conversation with one person/questions do not have to be repeated | Able to walk with help of another person |
Poor | Not able to watch television/vision problems cause some difficulties in ADL | Limited ability to have a conversation with one person/questions need to be repeated multiple times | Able to move independently in a wheelchair |
Very poor | Limited or complete loss of vision which causes severe difficulties in ADL | Not able to have a conversation with one person; this does not improve when speaking loud and clearly | Not able to move independently in a wheelchair |
Medical history
Condition-category | Conditions |
---|---|
Fraction of centenarians with at least one mention of this condition in their GP report (%) | Fraction of centenarians with a at least one mention of these conditions in their GP report (%) |
Cardiovascular disease (83.7%) Cardiovascular disease without hypertension (66.5%) | Hypertension (48.8%); congestive heart failure (29.7%); cardiac dysrhythmia (23%); CVA/TIA (18.7%); angina pectoris (15.3%); myocardial infarction (8.1%); valvular heart disease (8.1%); thrombosis (6.2%); pacemaker (5.7%); aortic stenosis (2.9%); amputation leg (1.4%); coronary bypass (1%); hypercholesterolemia (1%); arterial disease (0.5%); arteritis temporalis (0.5%); atherosclerosis (0.5%); cerebrovascular insufficiency (0.5%); coronary sclerosis (0.5%); intermittent claudication (0.5%); orthostatic hypotension (0.5%); pericarditis (0.5%) |
Musculoskeletal (63.2%) | Arthrosis (35.4%); fractures (34.4%); osteoporosis (14.8%); joint(s) replacement (11.5%); osteoarthritis (3.3%); hernia (1%) |
Vision (41.6%) | Cataract (30.1%); macular (7.7%); glaucoma (3.8%); vision impairment (2.4%) |
Hearing (30.6%) | Hearing impairment (30.6%); cholesteatoma (0.5%); sudden deafness (0.5%) |
Cancer (27.8%) | Skin cancer (17.2%); breast cancer (4.3%); colon cancer (4.3%); prostate cancer (1.9%); uterus cancer (1.4%); bladder cancer (0.5%); choleasteatome (0.5%); palate cancer (0.5%); stomach cancer (0.5%); thyroid cancer (0.5%); vocal chord cancer (0.5%) |
Autoimmunology (22%) | Diabetes (7.7%); rheumatoid arthritis (4.8%); hyperthyroidism (3.8%); hypothyroidism (3.3%); skin cancer (1.4%); asthma (1%); hypopituitarism (0.5%); thyroid enlargement (0.5%); thyroid removal (0.5%) |
Urology (21.5%) | UTI (7.2%); incontinence (5.7%); prostate hypertrophy (4.8%); hysterectomy (1.9%); uterine prolapse (1.9%); catheter (1%); prostate resection hypertrophy (1%); ovarian cysts (0.5%); |
Neurology/psychiatry (15.8%) | Balance (3.3%); cognitive decline (2.9%); depression (2.4%); psychiatry (2.4%); epilepsy (1.9%); delirium (1.4%); insomnia (1%); Parkinson’s (1%); dizziness (0.5%); migraine (0.5%); tremor (0.5%); WM atrophy (0.5%) |
Gastrointestinal (15.3%) | Kidney failure (6.7%); gastric ulcer (1.9%); cholecystectomy (1.4%); diverticulosis (1.4%); gall stones (1.4%); kidney stones (1%); reflux esophagitis (1%); appendectomy (0.5%); intestinal polyps (0.5%); pancreatitis (0.5%); rectal prolapse (0.5%); sigmoid resection (0.5%) |
Lung disease (10.5%) | Pneumonia (6.2%); COPD (2.4%); TBC (1.9%); Emphysema (0.5%); ulcer (0.5%) |
Other | Erysipelas (1.4%); anemia (1%); herpes zoster (1%); other (1%); restless legs (1%); eye infection (0.5%); itching (0.5%); pes equinus (0.5%); vitamin B deficiency (0.5%); vitiligo (0.5%) |
Cognitive profiling
Lifetime/demographic characteristics
Lifetime habits
Data-collection of first degree living centenarian-relatives and partners
Biomaterials
Biomaterial collection
Data storage
Cohort description
Included centenarians
Cohort statistics | ||
---|---|---|
100-plus cohort, June 2017 (N available, %)
| 300 | |
Age at inclusion (mean, SD) | 101.3 ± 1.7 | |
Birth years (median, IQR) | 1914 (1913–1915) | |
Brain donors (n, %) | 81 (27%) | |
Follow-up visits
| ||
T0 baseline visits | 300 | |
T1 possible visits (visited, died, missed) | 223 (140, 53, 30) | |
T2 possible visits (visited, died, missed) | 155 (48, 88, 19) | |
T3 possible visits (visited, died, missed) | 119 (11, 102, 6) |
Mortality | ||
---|---|---|
Whole cohort
| T0–T1 | T1–T2 |
Mortality rate (95% CI) | 0.24 (0.17–0.32) | 0.32 (0.20–0.49) |
Mortality percentage (95% CI) | 21% (16–27%) | 28% (18–39%) |
MMSE < 26 at baseline (95% CI)
| ||
Mortality rate (95% CI) | 0.29 (0.19–0.43) | 0.54 (0.29–0.90) |
Mortality percentage (95% CI) | 25% (17–35%) | 42% (25–59%) |
MMSE ≥ 26 at baseline (95% CI)
| ||
Mortality rate (95% CI) | 0.19 (0.11–0.29) | 0.19 (0.08–0.37) |
Mortality percentage (95% CI) | 17% (10–25%) | 17% (8–31%) |
Cognitive functioning at baseline | ||
---|---|---|
Mini Mental State Examination (MMSE)
| ||
100-plus cohort (median MMSE, IQR) | 25 (22.0–27.5) | |
MMSE > 22a (fraction of cohort, %) | 72.4% | |
MMSE ≥ 26 (fraction of cohort, %) | 47.2% | |
Estimated by trained researcher (n = 287)
| ||
Cognitively healthy (fraction of cohort, %; median MMSE (IQR) | 83%; 26 (23.5–28.0) | |
Doubt | 14%; 19 (16.4–22.0) | |
Cognitively impaired | 2.8%; 16.4 (12.8–17) |
Baseline presentation | ||
---|---|---|
Geriatric impairments
| ||
Mobile: without aids | 80.2% | |
Hearing: moderate-Good | 86.8% | |
Vision: moderate-Good | 77.1% | |
Maintained continence | 56.3% | |
Number of comorbidities (avg ± SD) | 3.7 ± 1.5 | |
Geriatric depression scale: ≤ 5 (no depression) | 91.5% | |
Living independence
| ||
Community dwelling/private residence with care available | 51.9% | |
Private quarters in residential care center | 42.0% | |
Independence in Activities of Daily Living (Barthel Index)
| ||
Needs minimal assistance (15–19) | 45.1% | |
Fully independent (20) | 32.4% |
Lifestyle characteristics | ||
---|---|---|
Smoking: regularly/often
| ||
Males | 67% | |
Females | 15% | |
Alcohol consumption: regularly/often
| ||
Males | 54% | |
Females | 31% |
Demographic characteristics | ||
---|---|---|
Education > basic (primary school)
| Centenarians versus populationb, c | |
Males | 79 versus 45% | |
Females | 66 versus 31% | |
Socioeconomic status
| ||
SEB: Social class father: ≥ lower-middle class | 31.2 versus 17.9% | |
SES: Social class-centenarian or –partner: ≥ lower-middle class | 55.5 versus 29.4% | |
Number of children parented: (mean ± SD)
| 3.9 ± 2.2 versus 3.5 ± 2.5 |
APOE genotypes | ||
---|---|---|
APOE genotypes
| Genotype frequency (%); centenarians versus populationd | Odds ratio (95% CI); p valuee |
ε2/ε2 | 0.9 versus 0.7% | 1.30 (0.3–5.7); p = 9.6 × 10−1 |
ε2/ε3 | 24.9 versus 11.7% | 2.49 (1.8–3.5); p = 3.4 × 10−7 |
ε2/ε4 | 4.8 versus 3.0% | 1.63 (0.8–3.1); p = 2.1 × 10−1 |
ε3/ε3 | 60.3 versus 60.5% | 0.99 (0.8–3.1); p = 8.9 × 10−1 |
ε3/ε4 | 8.7 versus 21.3% | 0.35 (0.2–0.6); p = 5.7 × 10−7 |
ε4/ε4 | 0.4 versus 2.9% | 0.15 (0.0–1.1); p = 3.2 × 10−3 |
APOE alleles
| ||
ε2 | 17 versus 10.7% | 2.1 (1.6–2.8); p = 4.8 × 10−7 |
ε3 | 86.1 versus 87.1% | 1.0 (0.8–1.3); p = 1.0 |
ε4 | 3.2 versus 7.5% | 0.44 (0.31–0.63); p = 6.3 × 10−7 |