Background
Methods
Study sample
Measurements
Biomaterial
Comorbidity
Lifestyle
Cognitive outcome measures
Statistical analyses
Spline regression analyses
Differences between age groups at baseline
Association of risk factors with cognitive outcome measures
Selection during follow-up
Statistical software
Results
Characteristic | Total sample | ≤70 years | > 70–80 years | > 80 years |
P
-value
b
|
---|---|---|---|---|---|
Sample sizea | 2527 | 1292 | 794 | 441 | |
Age, y | 70.1 (8.8) | 62.6 (4.2) | 75.5 (2.9) | 82.6 (1.5) | |
Female, % | 51.2 | 52.3 | 50.0 | 50.3 |
0.48
|
Education, y | 9.1 (3.4) | 9.5 (3.3) | 8.7 (3.2) | 8.6 (3.7) |
< 0.01
|
Follow-up, y (median, IQR) | 9.1 (3.2–19.0) | 13.3 (8.9–19.2) | 6.2 (3.0–13.0) | 4.9 (3.3–8.9) |
< 0.01
|
MMSE, points (median, IQR) | 28 (27–29) | 29 (26–30) | 28 (24–30) | 27 (24–30) |
< 0.01
|
Change in MMSE per year (SE) | −0.11 (0.00) | − 0.06 (0.00) | − 0.18 (0.01) | − 0.25 (0.02) |
< 0.01
|
15WT immediate recall, words | 8.1 (2.5) | 8.9 (2.3) | 7.6 (2.4) | 6.3 (2.1) |
< 0.01
|
Change in 15WT immediate recall per year (SE) | −0.11 (0.00) | −0.07 (0.00) | − 0.11 (0.01) | −0.07 (0.02) |
< 0.01
|
15WT delayed recall, words | 5.3 (2.7) | 6.2 (2.6) | 4.7 (2.5) | 3.5 (2.2) |
< 0.01
|
Change in 15WT delayed recall per year (SE) | −0.11 (0.00) | −0.05 (0.01) | − 0.10 (0.01) | −0.06 (0.02) |
< 0.01
|
APOE ε4, %c | 26.3 | 27.8 | 25.2 | 23.6 |
0.29
|
Total cholesterol, mmol/L | 5.7 (1.0) | 5.9 (1.0) | 5.6 (1.0) | 5.3 (1.1) |
< 0.01
|
LDL cholesterol, mmol/L | 3.7 (1.0) | 3.8 (0.9) | 3.6 (0.9) | 3.4 (1.1) |
< 0.01
|
HDL cholesterol, mmol/L | 1.3 (0.4) | 1.3 (0.4) | 1.4 (0.4) | 1.3 (0.4) |
0.48
|
Homocysteine, mmol/L | 14.5 (6.1) | 13.5 (5.2) | 14.7 (5.0) | 17.2 (9.2) |
< 0.01
|
Vitamin B12, pMol/L (median, IR) | 266 (212–333) | 268 (219–335) | 264 (213–331) | 249 (196–333) |
0.12
|
Hypertension, % | 76.7 | 72.9 | 82.2 | 73.7 |
< 0.01
|
Myocardial infarction, % | 8.8 | 6.4 | 11.1 | 11.7 |
< 0.01
|
Diabetes mellitus, % | 7.0 | 4.3 | 8.6 | 12.3 |
< 0.01
|
Stroke, % | 4.4 | 1.6 | 6.7 | 8.7 |
< 0.01
|
CES-D total score (median, IQR) | 5 (2–11) | 5 (2–9) | 6 (3–11) | 7 (3–12) |
< 0.01
|
IL-6, pg/ml (median, IQR) | 1.4 (0.6–2.5) | 1.3 (0.6–2.4) | 1.6 (0.7–2.7) | 1.8 (1.0–3.1) |
< 0.01
|
CRP, ug/ml (median, IQR) | 2.2 (1.0–4.7) | 2.0 (0.9–3.9) | 2.5 (1.3–5.6) | 2.8 (1.4–5.7) |
< 0.01
|
ACT, % of NHP | 173.6 (57.6) | 169.6 (53.0) | 179.3 (66.1) | 177.2 (54.1) |
0.01
|
Alcohol consumption, % | |||||
None | 20.1 | 15.6 | 25.3 | 24.7 |
< 0.01
|
Minimald | 20.6 | 17.8 | 23.6 | 23.6 | |
Moderatee | 59.4 | 66.6 | 51.1 | 51.7 | |
Smokers, % | 24.6 | 30.4 | 23.1 | 19.8 |
< 0.01
|
Total physical activity, min per day | 169.2 (114.2) | 188.4 (121.3) | 160.0 (103.7) | 126.8 (95.3) |
< 0.01
|
Determination of the best-fitted spline regression model
Differences between age groups at baseline
Association of risk factors with cognitive decline in the total sample
Risk factor | MMSE | 15WT immediate recall | 15WT delayed recall | ||||||
---|---|---|---|---|---|---|---|---|---|
B | SE |
P-value
| B | SE |
P-value
| B | SE |
P-value
| |
APOE ε4 | −0.25 | 0.24 |
< 0.01
| −0.07 | 1.27 |
0.49
| −0.09 | 1.44 |
0.42
|
Total cholesterol | 0.05 | 0.17 |
0.34
| 0.09 | 1.22 |
0.11
| 0.08 | 1.39 |
0.21
|
LDL cholesterol | 0.05 | 0.17 |
0.41
| 0.08 | 1.24 |
0.20
| 0.08 | 1.41 |
0.25
|
HDL cholesterol | 0.16 | 0.16 |
0.20
| 0.23 | 1.21 |
0.08
| 0.07 | 1.42 |
0.67
|
Homocysteine | −0.05 | 0.12 |
< 0.01
| −0.05 | 1.16 |
< 0.01
| − 0.06 | 1.33 |
< 0.01
|
Hypertension | 0.13 | 0.28 |
0.26
| −0.02 | 1.26 |
0.88
| −0.03 | 1.43 |
0.85
|
DM | −0.16 | 0.29 |
0.25
| −0.42 | 1.28 |
0.01
| −0.42 | 1.45 |
0.04
|
MI | 0.05 | 0.29 |
0.69
| 0.08 | 1.28 |
0.58
| 0.22 | 1.48 |
0.21
|
Stroke | −0.40 | 0.28 |
0.02
| −0.55 | 1.27 |
0.01
| −0.58 | 1.44 |
0.02
|
Depressive symptoms | −0.01 | 0.33 |
< 0.01
| −0.02 | 1.33 |
< 0.01
| −0.02 | 1.50 |
< 0.01
|
CRP | 0.00 | 0.27 |
0.57
| −0.01 | 1.27 |
0.15
| −0.01 | 1.45 |
0.47
|
IL-6 | 0.01 | 0.26 |
0.46
| 0.01 | 1.27 |
0.72
| 0.02 | 1.44 |
0.42
|
ACT | 0.00 | 0.27 |
0.68
| 0.00 | 1.27 |
0.74
| 0.00 | 1.45 |
0.87
|
Alcohola: minimalb | 0.27 | 0.10 |
< 0.01
| 0.35 | 0.12 |
< 0.01
| 0.35 | 0.14 |
0.01
|
Alcohola: moderatec | 0.24 | 0.08 |
< 0.01
| 0.41 | 0.10 |
< 0.01
| 0.42 | 0.12 |
< 0.01
|
Smoking | −0.09 | 0.25 |
0.26
| −0.16 | 1.27 |
0.09
| −0.03 | 1.46 |
0.77
|
Physical activity | 0.00 | 0.30 |
0.78
| 0.00 | 1.28 |
0.59
| 0.00 | 1.45 |
0.24
|
Age dependency of risk factors
Risk factor | MMSE | 15WT immediate recall | 15WT delayed recall | ||||||
---|---|---|---|---|---|---|---|---|---|
≤70 | > 70–80 | > 80 | ≤70 | > 70–80 | > 80 | ≤70 | > 70–80 | > 80 | |
APOE ε4 | 0.72 |
−4.24
|
−10.17
| −0.65 |
−3.85
|
−5.32
| 0.18 |
−4.15
|
−8.52
|
Total cholesterol | −3.37 | −0.10 | 1.26 | −1.08 | − 1.09 | 1.53 | 0.97 | −1.53 | 1.27 |
LDL cholesterol |
−5.40*
| 0.66 | 1.83* | −0.18 | −1.92* | 1.96* | 0.68 |
−2.62
| 1.41 |
HDL cholesterol | 7.35 | −2.17 | −1.07 | − 1.84 | 2.64 | 0.50 | 6.21 | 1.45 | 2.97 |
Homocysteine | 0.39 | −0.40 |
−0.92
| − 0.39 | − 0.21 | 0.13 | − 0.76* | −0.08 | 0.13* |
Hypertension | 0.04 | −2.14* |
6.52*
| −5.65* | −0.22 |
5.06*
| −4.04 | 3.54 | 0.43 |
DM | −0.95 | −0.46 | −9.32 | − 0.11 | −3.49 | −0.29 | −1.68 | −5.44 | 4.90 |
MI | 2.42 | −1.59 | 2.23 | 0.41 | 1.93 | 5.64 | 4.90 | 0.62 |
10.14
|
Stroke | 1.25 | −9.16* | 9.16* | 2.60 | −0.34 | 6.70 | 0.79 | −1.58 | −4.30 |
Depressive symptoms | −0.07 | 0.02 | −0.06 | −0.21 | 0.00 | 0.07 | −0.11* | −0.23 | 0.21* |
CRP | −0.18 | 0.18 | 0.19 | −0.21 | 0.03 | 0.19 | −0.19 | −0.11 | 0.16 |
IL-6 | 0.02* | −0.10* |
1.31*
| 0.27 | −0.11 | 0.64 | 0.31 | −0.03 | 0.88 |
ACT | 0.00 | 0.01 |
0.06
| −0.01 | − 0.01 | 0.03 | − 0.01* | −0.04 | 0.03* |
Alcohola: minimalb | 2.82* | −0.26 |
7.93*
| 3.19 | −3.09 | −0.31 | 5.91 | −3.03 | 0.25 |
Alcohola: moderatec | 0.78 | −0.95 | 3.48 | 2.85 | −3.51 | 1.42 | 3.19 | −0.47 | −0.69 |
Smoking | −0.30 | −1.05 | −5.15 |
−5.84*
| 0.53* | −1.13 |
−4.52
| −2.88 | −0.61 |
Physical activity | 0.00 | 0.00 |
0.02
| −0.01 | 0.01 | 0.00 | 0.01 | 0.01 | 0.00 |