Background
Methods
Study participants
Cognitive testing
Medical information and blood biochemistry
Apolipoprotein E genotyping
Scoring white matter and periventricular hyperintensities
Statistical analyses
Results
Participant characteristics
All | Male | Female | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Number | Data are mean ± SD, median [range] or (%) | p value | Number | Data are mean ± SD, median [range] or (%) | p value | Number | Data are mean ± SD, median [range] or (%) | p value | |||||||
Control | CD | Control | CD | Control | CD | Control | CD | Control | CD | Control | CD | ||||
Baseline | |||||||||||||||
Age (years) | 117 | 34 | 59.4 ± 5.9 | 61.2 ± 4.6 | 0.066 | 82 | 19 | 59.9 ± 6.2 | 61.2 ± 4.6 | 0.128 | 35 | 15 | 58.2 ± 5.3 | 59.9 ± 4.3 | 0.280 |
Sex (Female) | 35 | 15 | 29.9 (%) | 44.1 (%) | 0.148 | ||||||||||
BMI (kg/m2) | 117 | 34 | 22.3 ± 2.4 | 22.6 ± 3.3 | 0.590 | 82 | 19 | 22.5 ± 2.3 | 23.0 ± 2.1 | 0.379 | 35 | 15 | 21.8 ± 2.8 | 22.0 ± 4.4 | 0.844 |
SBP (mmHg) | 117 | 34 | 124 ± 18.6 | 124 ± 19.0 | 0.974 | 82 | 19 | 124 ± 15.7 | 130 ± 20.8 | 0.118 | 35 | 15 | 124 ± 24.4 | 116 ± 12.9 | 0.122 |
DBP (mmHg) | 117 | 34 | 72.8 ± 9.5 | 73.0 ± 10.9 | 0.916 | 82 | 19 | 73.8 ± 8.9 | 74.6. ± 12.5 | 0.804 | 35 | 15 | 70.4 ± 10.6 | 71.0 ± 8.43 | 0.852 |
Triglyceride (mg/dl) | 115 | 34 | 98.7 ± 52.3 | 103 ± 47.4 | 0.604 | 81 | 19 | 102 ± 56.2 | 120 ± 51.8 | 0.198 | 34 | 15 | 90.1 ± 40.8 | 82.7 ± 31.5 | 0.537 |
Total cholesterol (mg/dl) | 115 | 34 | 211 ± 30.1 | 224 ± 43.2 | 0.108 | 81 | 19 | 208 ± 28.8 | 209 ± 37.4 | 0.938 | 34 | 15 | 219 ± 32.2 | 244 ± 42.9 |
0.029
|
HDL-C (mg/dl) | 115 | 34 | 68.0 ± 18.4 | 63.5 ± 16.0 | 0.205 | 81 | 19 | 64.1 ± 18.4 | 55.7 ± 11.5 | 0.061 | 34 | 15 | 77.1 ± 15.2 | 73.4 ± 15.6 | 0.437 |
non-HDL-C (mg/dl) | 115 | 34 | 141 ± 37.7 | 161 ± 42.4 |
0.009
| 82 | 19 | 142 ± 36.5 | 153 ± 40.5 | 0.259 | 35 | 15 | 138 ± 40.8 | 171 ± 43.9 |
0.014
|
Total Protein (g/dl) | 115 | 34 | 7.14 ± 0.39 | 7.33 ± 0.33 |
0.012
| 81 | 19 | 7.11 ± 0.39 | 7.22 ± 0.31 | 0.276 | 34 | 15 | 7.22 ± 0.37 | 7.47 ± 0.32 |
0.027
|
Albumin (g/dl) | 115 | 34 | 4.40 ± 0.21 | 4.41 ± 0.19 | 0.751 | 81 | 19 | 4.42 ± 0.22 | 4.39 ± 0.23 | 0.626 | 34 | 15 | 4.36 ± 0.18 | 4.45 ± 0.15 | 0.137 |
A/G ratio | 99 | 30 | 1.87 ± 0.21 | 1.74 ± 0.16 |
0.002
| 71 | 18 | 1.91 ± 0.22 | 1.78 ± 0.16 |
0.025
| 28 | 12 | 1.78 ± 0.17 | 1.68 ± 0.16 | 0.084 |
Creatinine (mg/dl) | 115 | 34 | 0.94 ± 0.14 | 0.94 ± 0.23 | 0.850 | 81 | 19 | 1.00 ± 0.12 | 1.04 ± 0.25 | 0.277 | 34 | 15 | 0.81 ± 0.10 | 0.80 ± 0.11 | 0.816 |
Uric acid (mg/dl) | 115 | 34 | 5.47 ± 1.18 | 5.30 ± 1.37 | 0.466 | 81 | 19 | 5.89 ± 1.03 | 5.75 ± 1.54 | 0.620 | 34 | 15 | 4.47 ± 0.91 | 4.73 ± 0.87 | 0.369 |
HbA1c | 117 | 34 | 5.05 ± 0.77 | 5.34 ± 0.66 |
0.044
| 82 | 19 | 5.09 ± 0.71 | 5.43 ± 0.81 | 0.076 | 35 | 15 | 4.98 ± 0.88 | 5.24 ± 0.41 | 0.228 |
hsCRP (mg/dl) | 71 | 26 | 0.09 ± 0.07 | 0.11 ± 0.11 | 0.347 | 54 | 15 | 0.08 ± 0.07 | 0.13 ± 0.13 | 0.183 | 17 | 11 | 0.10 ± 0.08 | 0.08 ± 0.09 | 0.559 |
C. pneumoniae seropositivity | 39 | 14 | 33.3 (%) | 41.2 (%) | 0.420 | 25 | 11 | 30.5 (%) | 57.9 (%) |
0.034
| 14 | 3 | 40.0 (%) | 20.0 (%) | 0.209 |
H. pylori seropositivity | 58 | 27 | 49.6 (%) | 79.4 (%) |
0.003
| 37 | 15 | 45.1 (%) | 78.9 (%) |
0.010
| 21 | 12 | 60.0 (%) | 80.0 (%) | 0.209 |
ApoE4 carrier | 25 | 6 | 21.4 (%) | 17.7 (%) | 0.633 | 15 | 4 | 18.2 (%) | 21.1 (%) | 0.756 | 10 | 2 | 28.6 (%) | 13.3 (%) | 0.466 |
ApoE4 not determined | 2 | 1 | 1.71 (%) | 2.94 (%) | 2 | 0 | 2.43 (%) | 0 (%) | 0 | 1 | 0 (%) | 6.67 (%) | |||
Anamnesis | |||||||||||||||
Hypertension | 35 | 14 | 29.9 (%) | 41.2 (%) | 0.298 | 22 | 11 | 26.8 (%) | 57.9 (%) |
0.015
| 13 | 3 | 37.1 (%) | 20.0 (%) | 0.328 |
Hyperlipidemia | 18 | 6 | 15.3 (%) | 17.6 (%) | 0.793 | 15 | 5 | 18.3 (%) | 26.3 (%) | 0.525 | 3 | 1 | 8.57 (%) | 6.67 (%) | 1.000 |
Diabetes | 21 | 8 | 18.0 (%) | 23.5 (%) | 0.471 | 17 | 5 | 20.7 (%) | 26.3 (%) | 0.759 | 4 | 3 | 11.4 (%) | 20.0 (%) | 0.415 |
History of stroke | 1 | 0 | 0.86 (%) | 0 (%) | 1.000 | 0 | 0 | 0 (%) | 0 (%) | 1 | 0 | 2.86 (%) | 0 (%) | 1.000 | |
Education | |||||||||||||||
< 13 year | 53 | 23 | 45.3 (%) | 67.6 (%) |
0.049
| 32 | 12 | 39.0 (%) | 63.2 (%) | 0.122 | 21 | 11 | 60.0 (%) | 73.3 (%) | 0.526 |
≥ 13 year | 60 | 11 | 51.3 (%) | 32.4 (%) | 47 | 7 | 57.3 (%) | 36.8 (%) | 13 | 4 | 37.1 (%) | 26.7 (%) | |||
Not determined | 4 | 0 | 3.42 (%) | 0 (%) | 3 | 0 | 3.66 (%) | 0 (%) | 1 | 0 | 2.86 (%) | 0 (%) | |||
Alcohol drinking | |||||||||||||||
Current | 78 | 15 | 66.7 (%) | 44.1 (%) | 0.067 | 67 | 13 | 81.7 (%) | 68.4 (%) | 0.301 | 11 | 2 | 31.4 (%) | 13.3 (%) | 0.297 |
Former | 3 | 2 | 2.56 (%) | 5.88 (%) | 3 | 2 | 3.66 (%) | 10.5 (%) | 0 | 0 | 0 (%) | 0 (%) | |||
Never | 35 | 16 | 29.9 (%) | 47.0 (%) | 11 | 4 | 13.4 (%) | 21.1 (%) | 24 | 12 | 68.6 (%) | 80.0 (%) | |||
Not determined | 1 | 1 | 0.86 (%) | 2.94 (%) | 1 | 0 | 1.22 (%) | 0 (%) | 0 | 1 | 0 (%) | 6.67 (%) | |||
Smoking (%) | |||||||||||||||
Current | 21 | 7 | 17.9 (%) | 20.6 (%) | 0.758 | 20 | 7 | 24.4 (%) | 36.8 (%) | 0.561 | 1 | 0 | 2.86 (%) | 0 (%) | 0.221 |
Former | 40 | 9 | 34.2 (%) | 26.5 (%) | 40 | 8 | 48.8 (%) | 42.1 (%) | 0 | 1 | 0 (%) | 6.67 (%) | |||
Never | 54 | 16 | 46.2 (%) | 47.1 (%) | 21 | 4 | 25.6 (%) | 21.1 (%) | 33 | 12 | 94.3 (%) | 80.0 (%) | |||
Not determined | 2 | 2 | 1.71 (%) | 5.88 (%) | 1 | 0 | 1.22 (%) | 0 (%) | 1 | 2 | 2.86 (%) | 13.3 (%) | |||
In 2006-2008 | |||||||||||||||
MMSE | 117 | 34 | 29.5 ± 0.71 | 29.0 ± 0.75 |
<0.001
| 82 | 19 | 29.6 ± 0.64 | 29.3 ± 0.67 | 0.092 | 35 | 15 | 29.4 ± 0.85 | 28.6 ± 0.72 |
0.004
|
Ta | 117 | 34 | 10 [4-18] | 9 [4-18] | 0.274 | 82 | 19 | 10 [4-18] | 9 [4-18] | 0.501 | 35 | 15 | 10 [4-18] | 8 [4-18] | 0.469 |
Ka | 117 | 34 | 12 [2-21] | 11 [5-17] | 0.052 | 82 | 19 | 12 [4-21] | 11 [5-17] | 0.100 | 35 | 15 | 12 [2-21] | 10 [6-17] | 0.425 |
Pulse wave velocity (m/sec) | 116 | 34 | 15.2 ± 2.68 | 16.6 ± 2.73 |
0.013
| 81 | 19 | 15.4 ± 2.56 | 17.8 ± 2.94 |
<0.001
| 35 | 15 | 14.9 ± 2.95 | 14.9 ± 1.25 | 0.959 |
In 2012-2014 | |||||||||||||||
MMSE | 117 | 34 | 29.5 ± 0.67 | 26.0 ± 0.88 |
<0.001
| 82 | 19 | 29.6 ± 0.54 | 25.8 ± 0.87 |
<0.001
| 35 | 15 | 29.3 ± 0.87 | 26.1 ± 0.91 |
<0.001
|
Verbal fluency tasks | |||||||||||||||
Ta | 117 | 34 | 9 [2-17] | 8 [3-24] |
0.026
| 82 | 19 | 9 [2-15] | 8 [4-13] | 0.055 | 35 | 15 | 9 [2-17] | 8 [3-24] | 0.237 |
Ka | 117 | 34 | 10 [3-20] | 9 [5-18] |
0.038
| 82 | 19 | 10 [3-20] | 9 [5-18] | 0.440 | 35 | 15 | 10 [3-20] | 8 [5-14] |
0.017
|
Pulse wave velocity (m/sec) | 116 | 34 | 17.0 ± 2.99 | 18.5 ± 3.28 |
0.011
| 81 | 19 | 17.2 ± 2.65 | 19.4 ± 3.76 |
0.026
| 35 | 15 | 16.4 ± 3.64 | 17.4 ± 2.20 | 0.329 |
IADL | 117 | 34 | 13 [9-13] | 13 [7-13] | 0.463 | 81 | 19 | 13 [9-13] | 13 [9-13] | 0.595 | 35 | 15 | 13 [10-13] | 13 [7-13] | 0.580 |
METs | 117 | 34 | 14.5 [2.0-48.4] | 16.9 [1.5-50.4] | 0.161 | 81 | 19 | 15.2 [2.5-48.4] | 17.1 [1.5-50.4] | 0.195 | 35 | 15 | 14.5 [2.0-42.5] | 14.2 [1.5-40.0] | 0.335 |
Anamnesis | |||||||||||||||
Hypertension | 63 | 20 | 53.9 (%) | 58.8 (%) | 0.697 | 45 | 15 | 54.9 (%) | 78.9 (%) | 0.071 | 18 | 5 | 51.4 (%) | 33.3 (%) | 0.355 |
Hyperlipidemia | 61 | 25 | 52.1 (%) | 73.5 (%) |
0.031
| 41 | 14 | 50.0 (%) | 73.7 (%) | 0.076 | 20 | 11 | 57.1 (%) | 73.3 (%) | 0.351 |
Diabetes | 26 | 10 | 22.2 (%) | 29.4 (%) | 0.372 | 22 | 7 | 26.8 (%) | 36.8 (%) | 0.407 | 4 | 3 | 11.4 (%) | 20.0 (%) | 0.415 |
History of stroke | 6 | 1 | 5.13 (%) | 2.94 (%) | 0.822 | 4 | 1 | 4.88 (%) | 5.26 (%) | 1.000 | 2 | 0 | 5.71 (%) | 0 (%) | 0.640 |
Feel depression | |||||||||||||||
Nothing | 108 | 31 | 92.3 (%) | 91.2 (%) | 0.804 | 77 | 18 | 93.9 (%) | 94.7 (%) | 0.888 | 31 | 13 | 88.6 (%) | 86.7 (%) | 1.000 |
Sometimes | 8 | 3 | 6.84 (%) | 8.82 (%) | 4 | 1 | 4.88 (%) | 5.26 (%) | 4 | 2 | 11.4 (%) | 13.3 (%) | |||
Always | 1 | 0 | 0.86 (%) | 0 (%) | 1 | 0 | 1.22 (%) | 0 (%) | 0 | 0 | 0 (%) | 0 (%) |
Associations between CD and control participant characteristics
Number | Model I | Model II | Model III | |||||
---|---|---|---|---|---|---|---|---|
Control | CD | OR | 95% CI | OR | 95% CI | OR | 95% CI | |
DWL Baseline | ||||||||
grade 0 | 67 | 17 | Reference | Reference | Reference | |||
grade 1 | 44 | 17 | 1.476 | 0.669-3.255 | 1.684 | 0.715-3.967 | 1.451 | 0.573-3.671 |
DWL 1st follow-up | ||||||||
grade 0 | 52 | 11 | Reference | Reference | Reference | |||
grade 1 | 55 | 20 | 1.764 | 0.754-4.129 | 1.872 | 0.759-4.619 | 1.763 | 0.697-4.455 |
grade 2 | 8 | 3 | 1.314 | 0.620-2.787 | 1.458 | 0.598-3.557 | 1.049 | 0.299-3.387 |
DWL 2nd follow-up | ||||||||
grade 0 | 43 | 5 | Reference | Reference | Reference | |||
grade 1 | 50 | 21 |
3.659
|
1.242-10.77
|
4.562
|
1.382-15.05
|
4.427
|
1.323-14.81
|
grade 2 | 17 | 7 |
2.058
|
1.042-4.062
|
3.969
|
1.424-11.06
|
4.215
|
1.384-12.83
|
grade 3 | 6 | 1 | 1.008 | 0.450-2.259 | 0.807 | 0.273-2.384 | 1.103 | 0.274-4.442 |
PVH Baseline | ||||||||
grade 0 | 83 | 23 | Reference | Reference | Reference | |||
grade 1 | 29 | 11 | 1.156 | 0.479-2.791 | 0.848 | 0.327-2.197 | 0.700 | 0.254-1.930 |
PVH 1st follow-up | ||||||||
grade 0 | 66 | 18 | Reference | Reference | Reference | |||
grade 1 | 41 | 15 | 1.152 | 0.498-2.668 | 0.971 | 0.392-2.409 | 0.909 | 0.359-2.298 |
grade 2 | 8 | 1 | 0.591 | 0.192-1.815 | 0.611 | 0.188-1.988 | 0.632 | 0.191-2.095 |
PVH 2st follow-up | ||||||||
grade 0 | 61 | 17 | Reference | Reference | Reference | |||
grade 1 | 44 | 13 | 0.857 | 0.354-2.075 | 0.847 | 0.337-2.131 | 0.857 | 0.337-2.175 |
grade 2 | 7 | 4 | 1.450 | 0.716-2.937 | 1.254 | 0.554-2.842 | 1.221 | 0.524-2.841 |
Number | Model I | Model II | Model III | |||||
---|---|---|---|---|---|---|---|---|
Control | CD | OR | 95% CI | OR | 95% CI | OR | 95% CI | |
BMI | 117 | 34 | 1.073 | 0.998-1.154 | 1.060 | 0.910-1.235 | 1.024 | 0.868-1.207 |
SBP | 117 | 34 | 0.999 | 0.938-1.151 | 0.994 | 0.971-1.017 | 0.971 | 0.941-1.002 |
DBP | 117 | 34 | 1.010 | 0.970-1.052 | 0.998 | 0.954-1.044 | 0.997 | 0.941-1.036 |
Triglyceride | 115 | 34 | 1.003 | 0.996-1.011 | 1.002 | 0.994-1.010 | 1.002 | 0.989-1.015 |
Total cholesterol | 115 | 34 | 1.001 | 0.998-1.022 | 1.009 | 0.995-1.022 | 1.009 | 0.995-1.022 |
HDL-C | 115 | 34 |
0.972
|
0.946-0.999
| 0.977 | 0.950-1.004 | 0.973 | 0.942-1.005 |
non-HDL-C | 115 | 34 |
1.014
|
1.003-1.025
|
1.013
|
1.001-1.025
|
1.013
|
1.001-1.027
|
Total Protein | 115 | 34 |
2.971
|
1.023-8.622
|
3.575
|
1.088-11.74
| 3.219 | 0.938-11.04 |
Albumin | 115 | 34 | 2.035 | 0.291-14.21 | 1.980 | 0.243-16.12 | 1.852 | 0.218-15.71 |
A/G ratio | 99 | 30 |
0.063
|
0.006-0.619
|
0.032
|
0.003-0.379
|
0.037
|
0.003-0.470
|
Creatinine | 115 | 34 | 2.688 | 0.207-34.86 | 2.852 | 0.185-43.87 | 2.235 | 0.135-36.88 |
Uric acid | 115 | 34 | 1.007 | 0.695-1.459 | 1.037 | 0.707-1.520 | 1.068 | 0.730-1.563 |
HbA1c | 117 | 34 |
2.433
|
1.156-5.118
|
2.405
|
1.131-5.112
|
2.586
|
1.036-6.455
|
hsCRP | 71 | 26 | 12.95 | 0.104-1617 | 66.97 | 0.303-14824 | 42.42 | 0.127-14225 |
C. pneumoniae seropositivity | 117 | 34 | 1.297 | 0.580-2.899 | 1.437 | 0.619-3.336 | 1.593 | 0.664-3.82 |
H. pylori seropositive | 117 | 34 |
3.507
|
1.398-8.801
|
4.867
|
1.754-13.50
|
4.786
|
1.710-13.39
|
Pulse wave velocity in 2006-2008 | 116 | 34 |
1.184
|
1.021-1.371
|
1.209
|
1.028-1.422
| 1.179 | 0.989-1.404 |
Pulse wave velocity in 2012-2014 | 116 | 34 |
1.158
|
1.015-1.322
| 1.145 | 0.989-1.327 | 1.125 | 0.963-1.313 |
Education | 113 | 34 | 2.129 | 0.927-4.890 | ||||
ApoE4 carrier | 115 | 33 | 0.781 | 0.310-1.970 |
Multivariate | Stepwise forward selection | |||
---|---|---|---|---|
OR | 95% CI | OR | 95% CI | |
non-HDL-C | 1.011 | 0.999-1.024 | ||
A/G ratio | 0.265 | 0.022-3.215 |
0.092
|
0.010-0.887
|
HbA1c | 1.743 | 0.782-3.883 | ||
H. pylori seropositive |
4.255
|
1.422-12.73
|
4.468
|
1.535-13.00
|
Sex | 1.493 | 0.522-4.270 | ||
Age | 1.079 | 0.983-1.183 |
A/G ratio | ||
---|---|---|
Coefficient | p value | |
MMSE score in 2006-2008 | 0.187 |
0.034
|
MMSE score in 2012-2014 | 0.264 |
0.003
|
non-HDL-C | −0.230 |
0.009
|
HbA1c | −0.193 |
0.029
|
hsCRP | −0.369 |
0.001
|
Pulse wave velocity in 2006-2008 | −0.047 | 0.598 |
Pulse wave velocity in 2012-2014 | −0.001 | 0.989 |