Demographics and baseline characteristics
Detailed demographic and clinical characteristics of the participants were presented in Table 1. 40.2% of participants had metabolic syndrome. The mean age of the metabolic syndrome group was higher than the no metabolic syndrome group. The metabolic syndrome group had a higher proportion of females than the no metabolic syndrome group. The no metabolic syndrome group had a higher level of physical inactivity; however, they were also engaged in smoking and alcohol intake. The mortality rate of both groups was similar.
After eight years, of the 33,828 patients with metabolic syndrome, 1,380 patients (4.08%) converted to AD, and 335 patients (0.99%) converted to VD. Of the 50,316 patients without metabolic syndrome, 176 patients (0.35%) converted to AD, and 380 patients (0.76%) converted to VD.
Table 1. Demographics and baseline characteristics
|
Metabolic syndrome
(n=33,828)
|
No metabolic syndrome
(n=50,316)
|
p value
|
Mean age
|
67.42 ± 5.28
|
66.79 ± 5.11
|
<0.0001
|
Sex, female number(%)a
|
23,020 (68.1)
|
25,088 (49.9)
|
<0.0001
|
BMI
|
25.88 ± 2.96
|
23.68 ± 2.90
|
<0.0001
|
Systolic BP
|
136.61 ± 15.15
|
126.54 ± 15.91
|
<0.0001
|
Diastolic BP
|
82.03 ± 10.12
|
77.18 ± 9.97
|
<0.0001
|
Fasting glucose
|
112.14 ± 31.27
|
96.70 ± 20.45
|
0.001
|
Total cholesterol
|
200.80 ± 46.30
|
194.55 ± 38.46
|
<0.0001
|
Smoking, pack-year
|
1.33 ± 4.89
|
2.16 ± 5.99
|
<0.0001
|
Alcohol, cup/week
|
1.20 ± 2.94
|
1.54 ± 3.20
|
<0.0001
|
|
|
|
|
Previous stroke(%)a
|
804(2.38)
|
876(1.74)
|
<0.0001
|
Previous cardiac disease(%)a
|
2,137(62.2)
|
2,513(5.8)
|
<0.0001
|
Previous HTN(%)a
|
18,062(62.2)
|
17,180(39.6)
|
<0.0001
|
Previous DM(%)a
|
6,969(24.1)
|
4,102(9.5)
|
<0.0001
|
Previous dyslipidemia(%)a
|
2,225(7.7)
|
2,493(5.8)
|
<0.0001
|
|
|
|
|
Physical inactivity(%)a
|
5,487(29.8)
|
9,483(35.0)
|
<0.0001
|
|
|
|
|
High TG(%)a
|
21,746 (64.3)
|
7,617 (15.1)
|
<0.0001
|
High BP(%)a
|
27,571 (81.5)
|
22,848 (45.4)
|
<0.0001
|
High glucose(%)a
|
22,422 (33.7)
|
12,804 (74.6)
|
<0.0001
|
Abdominal obesity(%)a
|
26,806 (79.2)
|
14,939 (29.7)
|
<0.0001
|
Low HDL-C(%)a
|
19,768 (58.4)
|
8,377 (16.65)
|
<0.0001
|
Data are mean ± SD unless otherwise indicated
a Number (%)
Abbreviations: BMI, body mass index; SD, standard deviation; BP, blood pressure; HTN, hypertension; DM, diabetes mellitus; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol
Association between metabolic syndrome and AD
Table 2 showed the risk of AD according to the metabolic syndrome and component of the definition of metabolic syndrome.
Metabolic syndrome was associated with AD. (OR 11.48, 95% CI 9.03, 14.59, p<0.0001). Each of the five components of metabolic syndrome were also associated with AD. Patients with high TG had 1.87-fold odds of AD (OR 1.87, 95% CI 1.60, 2.19, p<0.001). Patients with high BP had 1.85-fold odds of AD (OR 1.85, 95% CI 1.55, 2.21, p<0.0001). Patients with high glucose levels had 1.77-fold odds of AD (OR 1.77, 95% CI 1.52, 2.06, p<0.0001). Patients with abdominal obesity had 1.88-fold odds of AD (OR 1.88, 95% CI 1.57, 2.25, p<0.0001). Patients with low HDL-C had 1.91-fold odds of AD (OR 1.91, 95% CI 1.63, 2.24, p<0.0001).
Table 2. Metabolic syndrome and odds of dementia in Alzheimer’s type
|
Model 1
|
|
Model 2
|
|
Model 3
|
|
|
OR (95% CI)
|
p value
|
OR (95% CI)
|
p value
|
OR (95% CI)
|
p value
|
MetS
|
10.58
(9.02,12.41)
|
<0.0001
|
12.03
(9.58,15.10)
|
<0.0001
|
11.48
(9.03,14.59)
|
<0.0001
|
Hight TG
|
2.64 (2.38,2.92)
|
<0.0001
|
2.00
(1.73,2.31)
|
<0.0001
|
1.87
(1.60,2.19)
|
<0.0001
|
High BP
|
1.87 (1.67,2.11)
|
<0.0001
|
1.78
(1.51,2.10)
|
<0.0001
|
1.85
(1.55,2.21)
|
<0.0001
|
High glucose
|
2.31
(2.08,2.54)
|
<0.0001
|
1.84
(1.60,2.12)
|
<0.0001
|
1.77
(1.52,2.06)
|
<0.0001
|
Abdominal obesity
|
2.37 (2.10,2.67)
|
<0.0001
|
1.77
(1.50,2.09)
|
<0.0001
|
1.88
(1.57,2.25)
|
<0.0001
|
Low HDL-C
|
2.33 (2.10,2.59)
|
<0.0001
|
1.95
(1.69,2.26)
|
<0.0001
|
1.91
(1.63,2.24)
|
<0.0001
|
Model 1: separate models associated each exposure variable with AD with adjustment for age and sex
Model 2: single model including age, sex, smoking, alcohol, physical inactivity, and metabolic syndrome or 5 metabolic syndrome components (high TG, high BP, high glucose, abdominal obesity, low HDL-C)
Model 3: single model including age, sex, smoking, alcohol, physical inactivity, previous stroke, previous cardiac disease, and metabolic syndrome or 5 metabolic syndrome components (high TG, high BP, high glucose, abdominal obesity, low HDL-C)
Abbreviations: OR, odds ratio; CI, confidence interval; MetS, metabolic syndrome; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; BP, blood pressure
Association between metabolic syndrome and VD
Table 3 showed the risk of VD according to the metabolic syndrome and component of the definition of metabolic syndrome.
Metabolic syndrome was not associated with VD (OR 1.17, 95% CI 0.94, 1.47, p=0.158). Among the five components of metabolic syndrome, high glucose was associated with VD. Patients with high glucose had 1.26-fold odds of VD (OR 1.26, 95% CI 1.01, 1.56, p=0.042). High TG, high BP, abdominal obesity, and low HDL-C were not associated with VD.
Table 3. Metabolic syndrome and odds of vascular dementia
|
Model 1
|
|
Model 2
|
|
Model 3
|
|
|
OR (95% CI)
|
p value
|
OR (95% CI)
|
p value
|
OR (95% CI)
|
p value
|
MetS
|
1.08
(1.02, 1.15)
|
0.006
|
1.17
(0.95, 1.45)
|
0.144
|
1.17
(0.94, 1.47)
|
0.158
|
Hight TG
|
1.03
(0.88, 1.20)
|
0.709
|
0.95
(0.76, 1.19)
|
0.631
|
0.90
(0.71, 1.14)
|
0.392
|
High BP
|
1.07
(0.92, 1.25)
|
0.404
|
1.31
(1.05, 1.64)
|
0.019
|
1.25
(0.99, 1.58)
|
0.066
|
High glucose
|
1.30
(1.11, 1.50)
|
0.001
|
1.29
(1.04, 1.59)
|
0.019
|
1.26
(1.01, 1.56)
|
0.042
|
Abdominal obesity
|
1.08
(0.92, 1.21)
|
0.362
|
0.97
(0.77, 1.21)
|
0.754
|
0.99
(0.78, 1.26)
|
0.939
|
Low HDL-C
|
1.03
(0.88, 1.20)
|
0.736
|
0.97
(0.77, 1.22)
|
0.806
|
0.97
(0.76, 1.23)
|
0.785
|
Model 1: separate models associated each exposure variable with VD with adjustment for age and sex
Model 2: single model including age, sex, smoking, alcohol, physical inactivity, and metabolic syndrome or 5 metabolic syndrome components (high TG, high BP, high glucose, abdominal obesity, low HDL-C)
Model 3: single model including age, sex, smoking, alcohol, physical inactivity, previous stroke, previous cardiac disease, and metabolic syndrome or 5 metabolic syndrome components (high TG, high BP, high glucose, abdominal obesity, low HDL-C)
Abbreviations: OR, odds ratio; CI, confidence interval; MetS, metabolic syndrome; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; BP, blood pressure
Association between metabolic syndrome and Any type of dementia
Table 4 showed the risk of any type of dementia according to the metabolic syndrome and component of the definition of metabolic syndrome.
Metabolic syndrome was associated with any type of dementia (OR 1.47, 95% CI 1.37, 1.57, p<0.0001). Among the five components of metabolic syndrome, high TG, high glucose, abdominal obesity, and low HDL-C were associated with any type of dementia. Patients with high TG had 1.16-fold odds of any type of dementia (OR 1.16, 95% CI 1.08, 1.24, p<0.0001). Patients with high glucose had 1.13-fold odds of any type of dementia (OR 1.13, 95% CI 1.05, 1.20, p<0.0001). Patients with abdominal obesity had 1.17-fold odds of any type of dementia (OR 1.17, 95% CI 1.09, 1.26, 0<0.0001). Patients with low HDL-C had 1.10-fold odds of any type of dementia (OR 1.10, 95% CI 1.03, 1.18, p=0.007).
Table 4. Metabolic syndrome and odds of any type of dementia
|
Model 1
|
|
Model 2
|
|
Model 3
|
|
|
OR (95% CI)
|
p value
|
OR (95% CI)
|
p value
|
OR (95% CI)
|
p value
|
MetS
|
1.44
(1.37, 1.50)
|
<0.0001
|
1.47
(1.39, 1.57)
|
<0.0001
|
1.47
(1.37, 1.57)
|
<0.0001
|
Hight TG
|
1.25
(1.20, 1.31)
|
<0.0001
|
1.19
(1.12, 1.27)
|
<0.0001
|
1.16
(1.08, 1.24)
|
<0.0001
|
High BP
|
1.04
(1.00, 1.09)
|
0.073
|
1.04
(0.97, 1.10)
|
0.264
|
1.06
(0.99, 1.14)
|
0.092
|
High glucose
|
1.19
(1.14, 1.24)
|
<0.0001
|
1.12
(1.06, 1.20)
|
<0.0001
|
1.13
(1.05, 1.20)
|
<0.0001
|
Abdominal obesity
|
1.22
(1.16, 1.28)
|
<0.0001
|
1.17
(1.09, 1.24)
|
<0.0001
|
1.17
(1.09, 1.26)
|
<0.0001
|
Low HDL-C
|
1.18
(1.12, 1.23)
|
<0.0001
|
1.12
(1.05, 1.19)
|
0.001
|
1.10
(1.03, 1.18)
|
0.007
|
Model 1: separate models associated each exposure variable with any type of dementia with adjustment for age and sex
Model 2: single model including age, sex, smoking, alcohol, physical inactivity, and metabolic syndrome or 5 metabolic syndrome components (high TG, high BP, high glucose, abdominal obesity, low HDL-C)
Model 3: single model including age, sex, smoking, alcohol, physical inactivity, previous stroke, previous cardiac disease, and metabolic syndrome or 5 metabolic syndrome components (high TG, high BP, high glucose, abdominal obesity, low HDL-C)
Abbreviations: OR, odds ratio; CI, confidence interval; MetS, metabolic syndrome; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; BP, blood pressure
Association between other cardiovascular risk factors included continuous metabolic parameters and dementia
BMI, fasting glucose, smoking, and previous stroke history were found associated with AD (Table 5). Patients with each 1-unit kg/m2 higher BMI had 0.951-fold odds of AD. (OR 0.951, 95% CI 0.927,0.975, p<0.0001) Patients with each 1-unit mg/dL higher fasting glucose had 1.003-fold odds of AD. (OR 1.003, 95% CI 1.001, 1.005, p=0.003) Patients with each 1-year higher pack/year smoking had 1.020-fold odds of AD (OR 1.020, 95% CI 1.003, 1.039, p=0.024). Patients with having previous stroke history had 1.827-fold odds of AD. (OR 1.827, 95% CI 1.263, 2.644, p=0.001).
Fasting glucose and previous stroke history were associated with VD. Patients with each 1-unit mg/dL higher fasting glucose had 1.004-fold odds of VD (OR 1.004, 95% CI 1.001, 1.008, p=0.012). Patients with having previous stroke history had 2.775-fold odds of VD. (OR 2.775, 95% CI 1.747, 4.406, p<0.0001).
Table 5. Odds of the dementia in Alzheimer’s type or VD according to vascular risk factors
|
Alzheimer’s disease
|
Vascular dementia
|
|
Model 1
|
Model 2
|
Model 3
|
Model 1
|
Model 2
|
Model 3
|
|
OR (95% CI)
|
p value
|
OR (95% CI)
|
p value
|
OR (95% CI)
|
p value
|
OR (95% CI)
|
p value
|
OR (95% CI)
|
p value
|
OR (95% CI)
|
p value
|
BMI
|
1.059
(1.042, 1.075)
|
<0.0001
|
0.958
(0.941, 0.975)
|
<0.0001
|
0.951 (0.927,0.975)
|
<0.0001
|
1.008
(0.984, 1.032)
|
0.528
|
0.998
(0.973, 1.023)
|
0.857
|
0.988
(0.952, 1.024)
|
0.504
|
Systolic BP
|
1.014
(1.011, 1.017)
|
<0.0001
|
1.000
(0.995, 1.004)
|
0.882
|
0.999
(0.992, 1.005)
|
0.651
|
1.000
(0.996, 1.005)
|
0.855
|
0.994
(0.988, 1.000)
|
0.063
|
0.999
(0.990, 1.008)
|
0.788
|
Diastolic BP
|
1.014
(1.009, 1.018)
|
<0.0001
|
0.996
(0.990, 1.002)
|
0.214
|
1.001
(0.991, 1.010)
|
0.916
|
1.007
(0.999, 1.014)
|
0.071
|
1.002
(1.002, 1.022)
|
0.019
|
1.004
(0.990, 1.019)
|
0.575
|
Fasting glucose
|
1.009
(1.008, 1.011)
|
<0.0001
|
1.004
(1.002, 1.005)
|
<0.0001
|
1.003
(1.001, 1.005)
|
0.003
|
1.005
(1.003, 1.007)
|
<0.0001
|
1.002
(1.002, 1.007)
|
<0.0001
|
1.004
(1.001, 1.008)
|
0.012
|
Total cholesterol
|
1.001
(1.000, 1.002)
|
0.003
|
1.001
(1.000, 1.002)
|
0.211
|
1.000
(0.998, 1.002)
|
0.793
|
1.000
(0.999, 1.002)
|
0.662
|
0.999
(0.999, 1.002)
|
0.793
|
1.000
(0.997, 1.003)
|
0.998
|
Smoking
|
1.007
(0.994, 1.021)
|
0.282
|
|
|
1.020
(1.003, 1.039)
|
0.024
|
0.928
(0.892, 0.966)
|
<0.0001
|
|
|
0.988
(0.962,1.014)
|
0.352
|
Alcohol
|
0.995
(0.969, 1.021)
|
0.694
|
|
|
0.979
(0.940, 1.019)
|
0.302
|
0.972
(0.936, 1.011)
|
0.155
|
|
|
1.014
(0.972,1.056)
|
0.525
|
Physical inactivity
|
0.935
(0.945, 1.163)
|
0.415
|
|
|
0.997
(0.838, 1.188)
|
0.977
|
0.974
(0.836, 1.136)
|
0.741
|
|
|
0.898
(0.700,1.153)
|
0.399
|
Previous stroke
|
2.248
(1.757, 2.874)
|
<0.0001
|
|
|
1.827
(1.263, 2.644)
|
0.001
|
2.461
(1.753, 3.445)
|
<0.0001
|
|
|
2.775
(1.747, 4.406)
|
<0.0001
|
Previous cardiac disease
|
1.213
(1.004, 1.467)
|
0.046
|
|
|
1.088
(0.836, 1.416)
|
0.532
|
0.825
(0.598, 1.139)
|
0.242
|
|
|
0.702
(0.434, 1.136)
|
0.150
|
Model 1: separate models associated each exposure variable with AD or VD with adjustment for age and sex
Model 2: single model including age, sex, metabolic syndrome, BMI, systolic BP, diastolic BP, fasting glucose, total cholesterol
Model 3: single model including age, sex, metabolic syndrome, BMI, systolic BP, diastolic BP, fasting glucose, total cholesterol, smoking, alcohol, physical inactivity, previous stroke and previous cardiac disease
Abbreviations: OR, odds ratio; CI, confidence interval; BMI, body mass index; BP, blood pressure