Background
4C study research objectives
Construction and content
Study design and participants
Inclusion criteria | The 4C–MCI cohort | The 4C–Dementia cohort |
• Cognitive performance | subjective cognitive complaints and/or objective cognitive impairments | objective cognitive impairments |
• Fulfil the DSM-IV diagnostic criteria for dementia [12] | No | Yes |
• Clinical Dementia Rating (CDR) Scale [34] | 0–0.5 | 0.5–2 |
• Mini Metal State Examination (MMSE) score [35] | Not specified | ≥10 |
• Age | ≥ 55 years | Not specified |
Exclusion criteria (similar for both cohorts) | ||
• The absence of a reliable informant (who has contact with the participant for at least once a week); | ||
• If the participant was expected unable to have at least one follow-up based on clinical judgment of the physician responsible for the care of the patient at the memory clinic; | ||
• The presence of other neurological disorders that could cause cognitive impairment or affect cognitive performance, such as Parkinson’s Disease, Huntington’s Disease, Normal Pressure Hydrocephalus (NPH), Korsakov’s syndrome, and a medical history of brain tumour, encephalitis or epilepsy. However, participants suffering from other cerebrovascular or psychiatric disorders were included in the studies. |
Data collection
Baseline | 12 months | 24 months | 36 months | Assessed by | Source | |
---|---|---|---|---|---|---|
Informed consent | √ | Research assistant | Participant and informant | |||
Demographics | √ | √ | √ | √ | Research assistant | Participant and informant |
MMSE [35] | √ | √ | √ | √ | Physician | Participant |
CDR [34] | √ | √ | √ | √ | Physician | Participant and informant |
Subjective cognitive functioning [17] | √ | √ | √ | √ | Physician | Informant |
Neuropsychological assessment | √ | √ | √ | √ | Psychologist | Participant |
Physical examination & structural medical review | √ | √ | √ | √ | Physician | Participant and informant |
Medications (prescribed & taken) | √ | √ | √ | √ | Physician | Participant and informant |
Hospitalization (if any) | √ | √ | √ | Research assistant | Participant and informant | |
Syndromal diagnoses | √ | √ | √ | √ | Physician | Participant and informant |
Comorbidities (CIRS-G) [18] | √ | √ | √ | √ | Physician | Participant and informant |
√ | √ | √ | √ | Research assistant | Participant and informant | |
DAD (disability assessment) [21] | √ | √ | √ | √ | Research assistant | Informant |
GDS-15 (depression, self-reported) [22] | √ | √ | √ | √ | Research assistant | Participant |
NPI (neuropsychiatric symptoms) [23] | √ | √ | √ | √ | Research assistant | Informant |
Euroqol 5D [24] | √ | √ | √ | √ | Research assistant | Informant |
Care resource use | √ | √ | √ | √ | Research assistant | Informant |
Refusal or withdrawal data | √ | √ | √ | √ | Research assistant | Participant and informant |
Institutionalization (outcome & date) | √ | √ | √ | Research assistant | Participant and informant | |
Death (outcome & date) | √ | √ | √ | Research assistant | Informant |
Syndrome diagnosis of MCI and dementia
Cognitive assessment
Cognitive domain(s) | Neuropsychological tests |
---|---|
Global cognition | Mini Mental State Examination (MMSE) [35] |
Episodic memory | 15-Word Verbal Learning Test (VLT) immediate recall (5 trails), delayed recall and delayed recognition [36] |
Implicit associative visual learning | Visual Association Test (VAT), short version [37] |
Working memory | Digit Span subtest (forwards and backwards) of the Wechsler Adult Intelligence Test (3rd Edition) [38] |
Verbal word fluency/semantic memory | 60 s animal fluency [39] |
Information processing speed | Letter Digit Substitution Test (LDST) [40] |
Information processing speed, attention and executive functioning/response inhibition | Stroop Color Word Test (SCWT) [41] |
Information processing speed, attention and executive functioning/concept shifting | Trail Making Test (TMT) parts A & B [42] |
Visual perception | Visual Object and Space Perception battery (VOSP, Optional) Subtests of dot counting and incomplete letters [43] |
Further assessments and questionnaires
Body systems | Concerned diseases |
---|---|
Cardiovascular | angina, myocardial infarction, angioplasty/stent, coronary bypass surgery, carotid stenosis, hypertension, heart failure, others |
Cerebrovascular | transient ischemic attack (TIA), cerebrovascular accidents (infarction, bleeding), reversible ischemic neurologic deficit (RIND), others |
Endocrinal | diabetes mellitus, hypothyroidism, hyperthyroidism, obesity, others |
Psychiatric | depression, psychosis, delirium, others |
Somatic | chronic obstructive pulmonary disease (COPD), kidney problems, liver problems, others |
Medications | the names, doses, frequencies and the indications of the medications |
Hospitalization | the primary diagnosis, acute or routine medical care, the treating department, the total number of nights spent in the hospital |
Refusal or withdrawal, minimum but essential data collected for research
Adaptations of study protocol and implementation
Utility and discussion
Results
N (%), unless stated differently | 4C-MCI cohort (n = 315) | 4C-Dementia cohort (n = 331) |
---|---|---|
Age at baseline (years, mean ± SD) | 69.7 ± 8.5 | 74.9 ± 10.2 |
Female sex | 111 (35) | 182 (55) |
Caucasian | 311 (99) | 326 (98) |
Education | ||
Low (lower than middle school) | 126 (40.0) | 142 (44.1) |
Middle (high school/vocational education) | 78 (24.8) | 90 (28.0) |
High (university) | 111 (35.2) | 90 (28.0) |
Marital Status | ||
Married/registered partnership, cohabiting | 244 (77.5) | 202 (61.2) |
Widow/widower | 42 (13.3) | 93 (28.2) |
Single, divorced | 29 (9.2) | 35 (10.6) |
Living situation | ||
Alone, independently | 59 (18.7) | 100 (30.5) |
With partner and/or children | 242 (76.8) | 205 (62.5) |
Institutionalized living | 9 (2.9) | 21 (6.4) |
Others | 5 (1.6) | 2 (0.6) |
Informant’s relation with the participant | ||
Partner | 224 (71.1) | 179 (54.4) |
Offspring | 60 (19.5) | 115 (35.0) |
Sibling | 7 (2.2) | 10 (3.0) |
Other relative or acquaintance | 23 (7.3) | 25 (7.6) |
Mean ± SD, unless stated differently | 4C-MCI cohort (n = 315) | 4C-Dementia cohort (n = 331) |
---|---|---|
Subclassification cognitive disorder, N (%)a | ||
Subjective cognitive decline | 90 (29) | n.a. |
Amnestic MCI | 151 (48) | n.a. |
Non-amnestic MCI | 71 (23) | n.a. |
Alzheimer’s disease (probable or possible) | n.a. | 216 (65) |
Vascular dementia or any dementia diagnosis with a vascular component | n.a. | 71 (21) |
Any other dementia diagnosis without a vascular component | n.a. | 44 (13) |
Self-reported duration of cognitive problems (years) | 3.3 ± 3.8 | 3.1 ± 2.6 |
Self-reported course of cognitive problems, N (%) | ||
Progressive | 213 (67.6) | 285 (89.1) |
Stable | 40 (12.7) | 14 (4.4) |
Fluctuated | 33 (10.5) | 21 (6.6) |
Cognitive functionsb | ||
MMSE (range 0–30, lower is worse) | 26.9 ± 2.6 | 21.9 ± 3.7 |
VLT immediate recall (z-score, lower is worse) | −1.1 ± 1.2 | −2.3 ± 1.1 |
VLT delayed recall (z-score, lower is worse) | −1.2 ± 1.3 | −2.4 ± 0.9 |
60 s animal fluency (z-score, lower is worse) | −0.7 ± 0.8 | −1.7 ± 0.9 |
TMT-A (z-score, lower is worse) | −0.3 ± 1.4 | −1.7 ± 1.9 |
TMT-B (z-score, lower is worse) | −0.4 ± 1.3 | −1.8 ± 1.4 |
SCWT card 1 + 2 (z-score, lower is worse) | −1.2 ± 1.7 | −2.8 ± 2.5 |
SCWT card 3 (z-score, lower is worse) | −1.2 ± 2.4 | −3.5 ± 3.2 |
Neuropsychiatric symptoms | ||
GDS-15 (range 0–15, higher is worse) | 3.6 ± 2.8 | 3.1 ± 2.7 |
NPI (range 0–144, higher is worse) | 14.5 ± 15.0 | 16.3 ± 16.3 |
BMI (kg/m2, mean ± SD) | 26.2 ± 3.9 | 25.9 ± 4.3 |
DAD (range 0–100, lower is worse) | 86.7 ± 15.7 | 70.8 ± 24.1 |
CIRS-G | ||
Total score (range 0–52c, higher is worse) | 7.09 ± 4.87 | 7.48 ± 4.94 |
Severity index (total score/number of categories endorsed, range 0–4, higher is worse) | 1.57 ± 0.51 | 1.63 ± 0.55 |
Comorbidity index (number of categories with score ≥2, range 0–13, higher is worse) | 2.25 ± 1.93 | 2.37 ± 1.90 |
CIRS-G category with score ≥2 (at least moderate disability or morbidity/requires “first line” therapy), N (%) | ||
Heart | 92 (29.2) | 90 (27.3) |
Vascular | 144 (45.7) | 170 (51.5) |
Hematopoietic | 12 (3.8) | 25 (7.6) |
Respiratory | 74 (23.5) | 54 (16.4) |
Eyes/ears/nose/throat | 54 (17.1) | 72 (21.8) |
Upper gastrointestinal | 48 (15.2) | 43 (13.0) |
Lower gastrointestinal | 28 (8.9) | 35 (10.6) |
Liver | 20 (6.3) | 21 (6.4) |
Renal | 15 (4.8) | 19 (5.8) |
Genitourinary | 57 (18.1) | 75 (22.7) |
Neuromuscular | 40 (12.7) | 70 (21.2) |
Neurological | 75 (23.8) | 48 (14.6) |
Endocrine | 49 (15.6) | 59 (17.9) |
Frailty according Fried Criteria, N (%) | ||
Not frail (≤1 of 5 criteria satisfied), | 219 (74.7) | 224 (68.9) |
Pre-frail (2 of 5 criteria satisfied) | 44 (15.0) | 55 (16.9) |
Frail (≥3 of 5 criteria satisfied) | 30 (10.2) | 46 (14.2) |
EQ-5D (with Dutch weights) (range 0–1, lower is worse) | 0.98 ± 0.06 | 0.81 ± 0.20 |
EQ-5D VAS (range 0–100, lower is worse) | 69.4 ± 15.6 | 67.5 ± 16.9 |
Study time line | Number of subjects | % | |
---|---|---|---|
MCI conversion to dementia | In the cohort | ||
1 year follow-up | 32 | 278 | 11.5 |
2 year follow-up | 18 | 260 | 6.9 |
3 year follow-up | 24 | 236 | 10.1 |
Total | 74 | 315 | 23.4 |