Fig. 1Incidence rates of (A) all-cause dementia, (B) Alzheimer's disease (AD), and (C) vascular dementia (VaD) based on age group.
Fig. 2Hazard ratios (HRs) for all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) based on (A) body mass index (BMI) or (B) waist circumference. Analyses were adjusted for age, sex, smoking, alcohol intake, exercise, income, plasma glucose concentration, duration of diabetes, dyslipidemia, hypertension, diabetic retinopathy, chronic kidney disease, stroke, ischemic heart disease, depression, number of oral hypoglycemic agents, and treatment with insulin.
Table 1Baseline characteristics of participants grouped based on the development of dementia
Characteristic |
Dementia |
P value |
No |
Yes |
Number |
1,824,944 |
92,758 |
|
Age, yr |
59.1±10.3 |
72.2±7.3 |
<0.001 |
Male sex |
1,074,414 (58.9) |
35,923 (38.7) |
<0.001 |
BMI, kg/m2
|
25.1±3.3 |
24.3±3.3 |
<0.001 |
WC, cm |
85.6±8.4 |
85.1±8.7 |
<0.001 |
Current smoker |
428,508 (23.5) |
11,135 (12.0) |
<0.001 |
Heavy drinker |
149,352 (8.2) |
3,201 (3.5) |
<0.001 |
Regular exercise |
881,117 (48.3) |
28,625 (30.9) |
<0.001 |
Income (lower 20%) |
398,762 (21.9) |
20,681 (22.3) |
0.001 |
FPG ≥126 mg/dL |
124,266 (68.1) |
51,398 (55.4) |
<0.001 |
Duration of diabetes ≥5 yr |
649,073 (35.6) |
48,059 (51.8) |
<0.001 |
Hypertension |
1,115,305 (61.1) |
70,535 (76.0) |
<0.001 |
Dyslipidemia |
818,380 (44.8) |
42,800 (46.1) |
<0.001 |
Diabetic retinopathy |
181,489 (9.9) |
13,960 (15.1) |
<0.001 |
CKD |
213,615 (11.7) |
25,680 (27.7) |
<0.001 |
Stroke |
42,827 (2.4) |
6,338 (6.8) |
<0.001 |
IHD |
107,463 (5.9) |
10,028 (10.8) |
<0.001 |
CVD |
142,589 (7.8) |
15,422 (16.6) |
<0.001 |
Depression |
108,996 (6.0) |
14,918 (16.1) |
<0.001 |
No. of OHAs |
|
|
<0.001 |
0 |
603,706 (33.1) |
18,096 (19.5) |
1 |
388,212 (21.3) |
22,761 (24.5) |
≥2 |
833,026 (45.7) |
51,901 (56.0) |
Insulin treatment |
163,683 (9.0) |
15,462 (16.7) |
<0.001 |
Table 2Multivariate Cox proportional analysis for development of any type of dementia, Alzheimer's disease, or vascular dementia
Characteristic |
Total |
ANY |
AD |
VaD |
Age |
1.13 (1.13–1.14) |
1.14 (1.14–1.14) |
1.11 (1.10–1.11) |
Female sex |
1.20 (1.18–1.22) |
1.26 (1.23–1.28) |
1.01 (0.96–1.06) |
Smoker |
|
|
|
Ex |
0.91 (0.89–0.93) |
0.92 (0.89–0.94) |
0.90 (0.85–0.96) |
Current |
1.15 (1.13–1.18) |
1.12 (1.09–1.15) |
1.34 (1.26–1.42) |
Drinker |
|
|
|
Mild |
0.83 (0.82–0.85) |
0.82 (0.80–0.84) |
0.86 (0.82–0.91) |
Heavy |
1.01 (0.97–1.04) |
0.99 (0.94–1.03) |
0.95 (0.86–1.04) |
Exercise |
0.80 (0.79–0.82) |
0.82 (0.80–0.83) |
0.75 (0.73–0.78) |
Income (lower 20%) |
1.10 (1.08–1.11) |
1.09 (1.07–1.11) |
1.09 (1.04–1.13) |
FPG ≥126 mg/dL |
0.98 (0.97–1.00) |
0.97 (0.95–0.99) |
1.03 (0.99–1.07) |
DM duration ≥5 yr |
1.13 (1.11–1.15) |
1.13 (1.11–1.15) |
1.11 (1.06–1.15) |
BMI, kg/m2
|
|
|
|
<18.5 |
1.26 (1.21–1.31) |
1.26 (1.21–1.32) |
1.13 (1.01–1.27) |
18.5–23 |
1 (reference) |
1 (reference) |
1 (reference) |
23–25 |
0.84 (0.83–0.86) |
0.84 (0.83–0.86) |
0.87 (0.83–0.91) |
25–30 |
0.78 (0.77–0.80) |
0.77 (0.76–0.79) |
0.84 (0.81–0.88) |
>30 |
0.75 (0.72–0.77) |
0.74 (0.71–0.77) |
0.80 (0.74–0.87) |
Hypertension |
1.06 (1.04–1.08) |
1.03 (1.01–1.05) |
1.26 (1.20–1.31) |
Dyslipidemia |
0.99 (0.98–1.00) |
0.99 (0.98–1.01) |
0.97 (0.94–1.01) |
Diabetic retinopathy |
1.09 (1.07–1.11) |
1.10 (1.07–1.12) |
1.08 (1.03–1.14) |
CKD |
1.16 (1.15–1.18) |
1.15 (1.13–1.17) |
1.18 (1.13–1.23) |
Stroke |
1.84 (1.79–1.88) |
1.57 (1.52–1.62) |
3.34 (3.16–3.53) |
IHD |
1.06 (1.04–1.08) |
1.07 (1.05–1.10) |
1.07 (1.01–1.13) |
Depression |
1.93 (1.89–1.96) |
1.94 (1.90–1.98) |
1.77 (1.68–1.86) |
No. of OHAs |
|
|
|
1 |
1.16 (1.14–1.18) |
1.15 (1.12–1.18) |
1.20 (1.14–1.27) |
≥2 |
1.04 (1.02–1.06) |
1.03 (1.01–1.06) |
1.09 (1.03–1.16) |
Insulin treatment |
1.52 (1.50–1.55) |
1.49 (1.45–1.52) |
1.62 (1.54–1.70) |
Table 3Multivariate Cox proportional analysis for development of any type of dementia, Alzheimer's disease, or vascular dementia based on 60 years of age
Characteristic |
<60 years |
≥60 years |
ANY |
AD |
VaD |
ANY |
AD |
VaD |
Age |
1.17 (1.17–1.18) |
1.20 (1.20–1.21) |
1.12 (1.11–1.13) |
1.11 (1.11–1.11) |
1.11 (1.11–1.12) |
1.08 (1.08–1.09) |
Female sex |
1.06 (1.01–1.12) |
1.13 (1.06–1.20) |
0.92 (0.83–1.03) |
1.23 (1.21–1.26) |
1.29 (1.26–1.32) |
1.04 (0.99–1.09) |
Smoker |
|
|
|
|
|
|
Ex |
0.85 (0.80–0.90) |
0.84 (0.78–0.90) |
0.87 (0.76–0.99) |
0.93 (0.91–0.96) |
0.94 (0.91–0.96) |
0.92 (0.86–0.98) |
Current |
1.24 (1.17–1.31) |
1.17 (1.09–1.25) |
1.43 (1.28–1.60) |
1.14 (1.11–1.17) |
1.12 (1.09–1.16) |
1.30 (1.22–1.39) |
Drinker |
|
|
|
|
|
|
Mild |
0.83 (0.80–0.87) |
0.83 (0.78–0.88) |
0.84 (0.76–0.93) |
0.85 (0.83–0.87) |
0.84 (0.81–0.86) |
0.89 (0.83–0.94) |
Heavy |
1.00 (0.93–1.08) |
0.98 (0.89–1.08) |
0.93 (0.80–1.09) |
1.04 (1.00–1.09) |
1.03 (0.98–1.09) |
0.97 (0.86–1.09) |
Exercise |
0.75 (0.73–0.78) |
0.75 (0.72–0.79) |
0.71 (0.66–0.77) |
0.81 (0.79–0.82) |
0.82 (0.81–0.84) |
0.76 (0.73–0.80) |
Low incomea
|
1.26 (1.21–1.30) |
1.28 (1.22–1.34) |
1.24 (1.14–1.35) |
1.07 (1.05–1.09) |
1.07 (1.05–1.09) |
1.04 (0.99–1.09) |
FPG ≥126 mg/dL |
0.95 (0.91–0.99) |
0.93 (0.89–0.97) |
0.99 (0.91–1.08) |
1.01 (0.99–1.02) |
0.99 (0.97–1.01) |
1.05 (1.01–1.10) |
DM duration ≥5 yr |
1.18 (1.14–1.23) |
1.18 (1.12–1.24) |
1.18 (1.08–1.29) |
1.10 (1.08–1.12) |
1.10 (1.08–1.12) |
1.07 (1.02–1.12) |
BMI <18.5 kg/m2
|
1.85 (1.64–2.07) |
1.94 (1.68–2.24) |
1.56 (1.18–2.06) |
1.26 (1.21–1.31) |
1.26 (1.20–1.33) |
1.10 (0.97–1.25) |
Hypertension |
1.19 (1.14–1.24) |
1.10 (1.05–1.16) |
1.50 (1.38–1.64) |
1.01 (1.00–1.03) |
0.99 (0.97–1.01) |
1.16 (1.10–1.21) |
Dyslipidemia |
0.97 (0.93–1.00) |
0.98 (0.93–1.02) |
1.00 (0.92–1.08) |
0.99 (0.97–1.00) |
0.99 (0.97–1.00) |
0.96 (0.92–1.00) |
Diabetic retinopathy |
1.13 (1.08–1.19) |
1.14 (1.07–1.21) |
1.19 (1.06–1.32) |
1.06 (1.03–1.08) |
1.06 (1.04–1.09) |
1.03 (0.97–1.09) |
CKD |
1.25 (1.19–1.31) |
1.23 (1.15–1.30) |
1.25 (1.12–1.40) |
1.17 (1.15–1.19) |
1.16 (1.14–1.18) |
1.18 (1.13–1.23) |
Stroke |
3.15 (2.96–3.36) |
2.62 (2.40–2.86) |
4.88 (4.32–5.51) |
1.67 (1.62–1.71) |
1.44 (1.39–1.49) |
3.03 (2.85–3.22) |
IHD |
1.16 (1.09–1.24) |
1.17 (1.08–1.27) |
1.27 (1.11–1.46) |
1.04 (1.01–1.06) |
1.05 (1.02–1.07) |
1.02 (0.96–1.09) |
Depression |
2.62 (2.50–2.75) |
2.74 (2.59–2.91) |
2.09 (1.87–2.34) |
1.81 (1.78–1.85) |
1.83 (1.79–1.87) |
1.68 (1.59–1.78) |
No. of OHAs |
|
|
|
|
|
|
1 |
1.08 (1.03–1.14) |
1.10 (1.03–1.17) |
1.08 (0.97–1.21) |
1.14 (1.11–1.16) |
1.11 (1.09–1.14) |
1.21 (1.14–1.28) |
≥2 |
0.99 (0.94–1.05) |
1.01 (0.94–1.09) |
0.95 (0.84–1.07) |
1.02 (0.99–1.04) |
1.00 (0.98–1.03) |
1.10 (1.03–1.18) |
Insulin treatment |
1.78 (1.69–1.86) |
1.78 (1.67–1.88) |
1.72 (1.55–1.90) |
1.46 (1.43–1.49) |
1.43 (1.39–1.46) |
1.57 (1.49–1.65) |