Background
Methods
Study design
Setting and data source
Participants
Follow-up period
Main outcome
Risk factor measurements
Analysis
Sample size calculation
Missing data imputation
Development cohort: model development
Validation cohort: validation and calibration
Results
Development cohort study
Development cohort aged 60–79 years
Development cohort n = 800,013 Median follow-up 5 years (IQR, 3.15–5 years) Dementia events n = 6,017 | Validation cohort n = 226,140 Median follow-up 5 years (IQR, 3.27–5 years) Dementia events n = 1,699 | |||||
---|---|---|---|---|---|---|
Obs | Mean | SD | Obs | Mean | SD | |
Baseline age, years | 800,013 | 65.6 | 6.08 | 226,140 | 65.6 | 6.11 |
Baseline total cholesterol, mmol/L | 242,045 | 5.21 | 1.13 | 64,832 | 5.25 | 1.13 |
Baseline HDL cholesterol, mmol/L | 167,937 | 1.42 | 0.41 | 45,682 | 1.42 | 0.42 |
Baseline weight, kg | 226,671 | 79.2 | 16.9 | 59,594 | 79.1 | 16.8 |
Baseline systolic blood pressure, mmHg | 452,306 | 142.4 | 17.0 | 125,744 | 142.7 | 17.1 |
Height, m | 553,195 | 1.67 | 0.10 | 159,136 | 1.67 | 0.10 |
Baseline BMI, kg/m2
| 193,524 | 28.5 | 5.44 | 51,590 | 28.4 | 5.36 |
Baseline lipid ratio | 166,420 | 3.88 | 1.17 | 45,352 | 3.91 | 1.17 |
Obs | Freq | % | Obs | Freq | % | |
Sex | 800,013 | 226,140 | ||||
Men | 386,039 | 48.3 | 109,108 | 48.3 | ||
Women | 413,974 | 51.8 | 117,032 | 51.8 | ||
Local area deprivation score (quintiles) | 800,013 | 226,140 | ||||
1 (=least deprived) | 218,198 | 27.3 | 71,040 | 31.4 | ||
2 | 194,637 | 24.3 | 57,763 | 25.5 | ||
3 | 166,956 | 20.9 | 42,278 | 18.7 | ||
4 | 134,103 | 16.8 | 33,945 | 15.0 | ||
5 (=most deprived) | 86,119 | 10.8 | 21,114 | 9.3 | ||
Baseline smoking status | 756,115 | 213,419 | ||||
Never | 323,345 | 42.8 | 96,256 | 45.1 | ||
Past | 286,763 | 37.9 | 78,608 | 36.8 | ||
Current | 146,007 | 19.3 | 38,555 | 18.1 | ||
History of very heavy drinking/alcohol problem | 800,013 | 22,308 | 2.8 | 226,140 | 6,011 | 2.7 |
History of diabetes | 800,013 | 70,377 | 8.8 | 226,140 | 18,662 | 8.3 |
History of coronary heart disease | 800,013 | 93,408 | 11.7 | 226,140 | 26,016 | 11.5 |
History of stroke or transient ischemic attack | 800,013 | 38,976 | 4.9 | 226,140 | 10,930 | 4.8 |
History of atrial fibrillation | 800,013 | 24,763 | 3.1 | 226,140 | 7,085 | 3.1 |
Depression or use of anti-depressants at baseline | 800,013 | 83,464 | 10.4 | 226,140 | 23,583 | 10.4 |
Anxiety or use of anxiolytics at baseline | 800,013 | 29,690 | 3.7 | 226,140 | 8,549 | 3.8 |
Use of anti-hypertensive drugs at baseline | 800,013 | 274,657 | 34.3 | 226,140 | 75,359 | 33.3 |
Use of statins at baseline | 800,013 | 151,275 | 18.9 | 226,140 | 39,738 | 17.6 |
Use of hypnotics at baseline | 800,013 | 30,787 | 3.9 | 226,140 | 8,736 | 3.9 |
Use of NSAIDs (other than aspirin) at baseline | 800,013 | 98,397 | 12.3 | 226,140 | 27,546 | 12.2 |
Use of aspirin at baseline | 800,013 | 127,550 | 15.9 | 226,140 | 34,756 | 15.4 |
Coefficienta
| 95 % CI | HRa
| 95 % CI | |
---|---|---|---|---|
Age, per year increase | 0.209 | 0.200 to 0.219 | 1.23 | 1.22 to 1.25 |
Age2, per unit increase | −0.003 | −0.004 to −0.003 | 0.997 | 0.996 to 0.997 |
Gender (female vs. male) | 0.129 | 0.074 to 0.183 | 1.14 | 1.08 to 1.20 |
Calendar year, per year increase | 0.045 | 0.035 to 0.054 | 1.05 | 1.04 to 1.06 |
Local area deprivation score (quintile) | ||||
1 (=least deprived) | 0 | 1 | ||
2 | 0.013 | −0.063 to 0.090 | 1.01 | 0.94 to 1.09 |
3 | 0.118 | 0.041 to 0.194 | 1.13 | 1.04 to 1.22 |
4 | 0.202 | 0.123 to 0.280 | 1.22 | 1.13 to 1.32 |
5 (=most deprived) | 0.226 | 0.138 to 0.314 | 1.25 | 1.15 to 1.37 |
BMI (kg/m2), per unit increase | −0.062 | −0.069 to −0.054 | 0.94 | 0.93 to 0.95 |
BMI2, per unit increase | 0.003 | 0.002 to 0.003 | 1.003 | 1.002 to 1.003 |
Current anti-hypertensive use (yes vs. no) | −0.132 | −0.190 to −0.074 | 0.88 | 0.83 to 0.93 |
Smoking status | ||||
Never | 0 | 1 | ||
Past | −0.068 | −0.127 to −0.009 | 0.93 | 0.88 to 0.99 |
Current | −0.087 | −0.168 to −0.005 | 0.92 | 0.85 to 1.00 |
History of alcohol problem (yes vs. no) | 0.444 | 0.287 to 0.600 | 1.56 | 1.33 to 1.82 |
History of diabetes (yes vs. no) | 0.287 | 0.205 to 0.368 | 1.33 | 1.23 to 1.45 |
Current depression/use of anti-depressants (yes vs. no) | 0.834 | 0.770 to 0.897 | 2.30 | 2.16 to 2.45 |
History of stroke or transient ischemic attack (yes vs. no) | 0.577 | 0.500 to 0.654 | 1.78 | 1.65 to 1.92 |
History of atrial fibrillation (yes vs. no) | 0.221 | 0.120 to 0.322 | 1.25 | 1.13 to 1.38 |
Current aspirin use (yes vs. no) | 0.253 | 0.189 to 0.316 | 1.29 | 1.21 to 1.37 |
Development cohort aged 80–95 years
Development cohort n = 130,382 Median follow-up 3.76 years (IQR, 1.71–5 years) Dementia events n = 7,104 | Validation cohort n = 38,084 Median follow-up 3.92 years (IQR, 1.75–5 years) Dementia events n = 1,923 | |||||
---|---|---|---|---|---|---|
Obs | Mean | SD | Obs | Mean | SD | |
Baseline age, years | 130,382 | 84.8 | 3.93 | 38,084 | 84.9 | 3.97 |
Baseline total cholesterol, mmol/L | 26,841 | 4.99 | 1.19 | 6,785 | 5.08 | 1.21 |
Baseline HDL cholesterol, mmol/L | 16,630 | 1.50 | 0.44 | 4,066 | 1.49 | 0.44 |
Baseline weight, kg | 31,272 | 67.1 | 14.0 | 8,038 | 67.2 | 13.8 |
Baseline systolic blood pressure, mmHg | 78,979 | 146.9 | 19.8 | 22,347 | 147.5 | 19.8 |
Height, m | 62,622 | 1.62 | 0.10 | 17,616 | 1.62 | 0.10 |
Baseline BMI, kg/m2
| 24,091 | 25.7 | 4.65 | 6,213 | 25.7 | 4.53 |
Baseline lipid ratio | 16,566 | 3.49 | 1.10 | 4,054 | 3.57 | 1.13 |
Obs | Freq | % | Obs | Freq | % | |
Sex | 130,382 | 38,084 | ||||
Men | 44,286 | 34.0 | 13,017 | 34.2 | ||
Women | 86,096 | 66.0 | 25,067 | 65.8 | ||
Local area deprivation score (quintiles) | 130,382 | 38,084 | ||||
1 (=least deprived) | 26,643 | 20.4 | 10,048 | 26.4 | ||
2 | 30,143 | 23.1 | 9,307 | 24.4 | ||
3 | 28,970 | 22.2 | 7,830 | 20.6 | ||
4 | 26,758 | 20.5 | 6,644 | 17.5 | ||
5 (=most deprived) | 17,868 | 13.7 | 4,255 | 11.2 | ||
Baseline smoking status | 113,391 | 32,702 | ||||
Never | 63,684 | 56.2 | 19,389 | 59.3 | ||
Past | 39,778 | 35.1 | 10,697 | 32.7 | ||
Current | 9,929 | 8.8 | 2,616 | 8.0 | ||
History of very heavy drinking/alcohol problem | 130,382 | 921 | 0.7 | 38,084 | 250 | 0.7 |
History of diabetes | 130,382 | 12,762 | 9.8 | 38,084 | 3,331 | 8.8 |
History of coronary heart disease | 130,382 | 28,190 | 21.6 | 38,084 | 8,281 | 21.7 |
History of stroke or transient ischemic attack | 130,382 | 20,221 | 15.5 | 38,084 | 5,824 | 15.3 |
History of atrial fibrillation | 130,382 | 14,518 | 11.1 | 38,084 | 4,293 | 11.3 |
Depression or use of anti-depressants at baseline | 130,382 | 17,201 | 13.2 | 38,084 | 4,886 | 12.8 |
Anxiety or use of anxiolytics at baseline | 130,382 | 5,953 | 4.6 | 38,084 | 1,816 | 4.8 |
Use of anti-hypertensive drugs at baseline | 130,382 | 58,323 | 44.7 | 38,084 | 16,396 | 43.1 |
Use of statins at baseline | 130,382 | 16,546 | 12.7 | 38,084 | 4,111 | 10.8 |
Use of hypnotics at baseline | 130,382 | 14,121 | 10.8 | 38,084 | 4,137 | 10.9 |
Use of NSAIDs (other than aspirin) at baseline | 130,382 | 15,056 | 11.6 | 38,084 | 4,430 | 11.6 |
Use of aspirin at baseline | 130,382 | 41,448 | 31.8 | 38,084 | 11,830 | 31.1 |
Coefficienta
| 95 % CI | HRa
| 95 % CI | |
---|---|---|---|---|
Age, per year increase | 0.055 | 0.047 to 0.062 | 1.06 | 1.05 to 1.06 |
Age2, per unit increase | −0.005 | −0.007 to −0.004 | 0.995 | 0.993 to 0.996 |
Gender (female v male) | 0.160 | 0.104 to 0.216 | 1.17 | 1.11 to 1.24 |
Calendar year, per year increase | 0.074 | 0.063 to 0.084 | 1.08 | 1.07 to 1.09 |
BMI (kg/m2), per unit increase | −0.050 | −0.063 to-0.036 | 0.95 | 0.94 to 0.96 |
Current anti-hypertensive use (yes vs. no) | −0.249 | −0.301 to −0.197 | 0.78 | 0.74 to 0.82 |
Systolic blood pressure (mmHg), per unit increase | −0.006 | −0.008 to −0.005 | 0.994 | 0.992 to 0.995 |
Lipid ratio (per unit increase) | 0.042 | −0.055 to 0.138 | 1.04 | 0.95 to 1.15 |
Smoking status | ||||
Never | 0 | 1 | ||
Past | −0.178 | −0.233 to −0.122 | 0.84 | 0.79 to 0.89 |
Current | −0.134 | −0.229 to −0.039 | 0.88 | 0.80 to 0.96 |
History of alcohol problem (yes vs. no) | 0.256 | −0.009 to 0.521 | 1.29 | 0.99 to 1.68 |
History of diabetes (yes vs. no) | 0.183 | 0.102 to 0.264 | 1.20 | 1.11 to 1.30 |
History of stroke or transient ischemic attack (yes vs. no) | 0.242 | 0.177 to 0.306 | 1.27 | 1.19 to 1.36 |
History of atrial fibrillation (yes vs. no) | 0.057 | −0.018 to 0.132 | 1.06 | 0.98 to 1.14 |
Current depression/use of anti-depressants (yes vs. no) | 0.400 | 0.335 to 0.465 | 1.49 | 1.40 to 1.59 |
Current anxiety/use of anxiolytics (yes vs. no) | 0.136 | 0.034 to 0.237 | 1.15 | 1.04 to 1.27 |
Current NSAID use, excluding aspirin (yes vs. no) | −0.157 | −0.237 to −0.078 | 0.86 | 0.79 to 0.93 |
Current aspirin use (yes vs. no) | 0.092 | 0.037 to 0.147 | 1.10 | 1.04 to 1.16 |
Validation cohort study
Validation cohort aged 60–79 years
Cut off for high risk | Sensitivity | Specificity | PPV | NPV | Patients classified as high risk, n (%) | Patients classified as high risk who develop dementia, n (%) | Patients classified as low risk, n (%) | Patients classified as low risk who develop dementia, n (%) |
---|---|---|---|---|---|---|---|---|
1 % | 77.70 | 73.05 | 2.14 | 99.77 | 61,803 (27.33) | 1,320 (2.14) | 164,337 (72.67) | 379 (0.23) |
2 % | 58.36 | 85.15 | 2.89 | 99.63 | 34,323 (15.18) | 992 (2.89) | 191,817 (84.82) | 707 (0.37) |
5 % | 19.39 | 97.03 | 4.71 | 99.38 | 6,989 (3.09) | 329 (4.71) | 219,151 (96.91) | 1,370 (0.62) |
10 % | 5.62 | 99.52 | 8.20 | 99.29 | 1,164 (0.51) | 95 (8.2) | 224,976 (99.49) | 1,604 (0.71) |
20 % | 0.72 | 99.96 | 10.87 | 99.25 | 113 (0.05) | 12 (10.87) | 226,027 (99.95) | 1,687 (0.75) |