Table 1. Descriptive characteristics of the study population
|
No. (%) of Participants, Vascular Risk Factors
|
|
|
Total (n=178,586)
|
AD
(n=10,732)
|
Non-AD (n=167,854)
|
P-value
|
Sex *
|
|
|
|
<0.0001
|
Male
|
81242 (45.5)
|
3742 (34.9)
|
77500 (46.2)
|
|
Female
|
97344 (54.5)
|
6990 (65.1)
|
90354 (53.8)
|
|
Age group *
|
|
|
|
<0.0001
|
65 to 69 years
|
23471 (13.1)
|
74 (0.7)
|
23397 (13.9)
|
|
70 to 74 years
|
80333 (45.0)
|
2352 (21.9)
|
77981 (46.5)
|
|
75 to 79 years
|
48208 (27.0)
|
3898 (36.3)
|
44310 (26.4)
|
|
Older than 80 years
|
26574 (14.9)
|
4408 (41.1)
|
22166 (13.2)
|
|
Income, deciles *
|
|
|
|
<0.0001
|
Medical Aid
|
1899 (1.1)
|
258 (2.4)
|
1641 (1.0)
|
|
Low (1st–3rd decile)
|
36433 (20.4)
|
2037 (19.0)
|
34396 (20.5)
|
|
Middle (4th–7th decile)
|
48421 (27.1)
|
2832 (26.4)
|
45589 (27.2)
|
|
High (8th–10th decile)
|
91833 (51.4)
|
5605 (52.2)
|
86228 (51.4)
|
|
Life styles *
|
|
|
|
|
Smoking status *
|
|
|
|
<0.0001
|
Never smoking
|
130940 (73.3)
|
8475 (79.0)
|
122465 (73.0)
|
|
Ex-smoking
|
26613 (14.9)
|
1230 (11.5)
|
25383 (15.1)
|
|
Current smoking
|
21033 (11.8)
|
1027 (9.6)
|
20006 (11.9)
|
|
Alcohol consumption *
|
|
|
|
<0.0001
|
Rarely (0–2 days/week)
|
158170 (88.6)
|
9795 (91.3)
|
148375 (88.4)
|
|
Light (3–4 days/week)
|
9275 (5.2)
|
376 (3.5)
|
8899 (5.3)
|
|
Heavy (5–7 days/week)
|
11141 (6.2)
|
561 (5.2)
|
10580 (6.3)
|
|
Exercise *
|
|
|
|
<0.0001
|
No exercise
|
121405 (68.0)
|
7795 (72.6)
|
113610 (67.7)
|
|
Exercise
|
57181 (32.0)
|
2937 (27.4)
|
54244 (32.3)
|
|
Co-morbidities *
|
|
|
|
|
Depression *
|
14075 (7.9)
|
1270 (11.8)
|
12805 (7.6)
|
<0.0001
|
Charlson co-morbidity Index *
|
|
|
|
|
0
|
21574 (12.1)
|
975 (9.1)
|
20599 (12.3)
|
<0.0001
|
1
|
40912 (22.9)
|
2014 (18.8)
|
38898 (23.2)
|
|
≥ 2
|
116100 (65.0)
|
7743 (72.2)
|
108357 (64.6)
|
|
Health care visit frequency *,†
|
|
|
|
<0.0001
|
First quartile
|
44748 (25.1)
|
1904 (17.7)
|
42844 (25.5)
|
|
Second quartile
|
44669 (25.0)
|
2325 (21.7)
|
42344 (25.2)
|
|
Third quartile
|
44595 (25.0)
|
2751 (25.6)
|
41844 (24.9)
|
|
Fourth quartile
|
44574 (25.0)
|
3752 (35.0)
|
40822 (24.3)
|
|
Medication history *
|
|
|
|
|
HMG-CoA reductase inhibitors
|
41904 (23.5)
|
2611 (24.3)
|
39293 (23.4)
|
0.029
|
Antidiabetic medication
|
28439 (15.9)
|
2056 (19.2)
|
26383 (15.7)
|
<0.0001
|
Antihypertensive medication
|
106098 (59.4)
|
6101 (62.4)
|
99397 (59.2)
|
<0.0001
|
Antidepressants
|
10318 (5.8)
|
1028 (9.6)
|
9290 (5.5)
|
<0.0001
|
Benzodiazepine and sleep pill
|
47203 (26.4)
|
3835 (35.7)
|
43368 (25.8)
|
<0.0001
|
Antiplatelet medication
|
50994 (28.6)
|
3491 (32.5)
|
47503 (28.3)
|
<0.0001
|
Laboratory findings
|
|
|
|
|
Cholesterol level, mean (SD), mg/dL ‡
|
|
|
|
|
Total cholesterol
|
196.4 (38.4)
|
198.6 (39.3)
|
196.3 (38.4)
|
<0.0001
|
LDL-C
|
116.2 (35.3)
|
117.6 (35.8)
|
116.1 (35.2)
|
<0.0001
|
HDL-C
|
52.8 (13.4)
|
52.9 (13.7)
|
52.8 (13.4)
|
0.211
|
Triglyceride
|
135.6 (68.6)
|
138.6 (69.9)
|
135.4 (68.5)
|
<0.0001
|
Fasting glucose
|
101.9 (21.0)
|
102.8 (22.3)
|
101.9 (20.9)
|
<0.0001
|
Hemoglobin
|
13.3 (1.5)
|
13.0 (1.4)
|
13.3 (1.5)
|
<0.0001
|
Physical examination findings, mean (SD), mmHg ‡
|
|
|
|
Systolic blood pressure
|
130.3 (15.9)
|
130.4 (16.4)
|
130.3 (15.9)
|
0.534
|
Diastolic blood pressure
|
78.0 (9.8)
|
78.1 (10.1)
|
78.1 (9.8)
|
0.728
|
Body Mass Index, kg/m2
|
23.8 (3.1)
|
23.5 (3.2)
|
23.8 (3.1)
|
<0.0001
|
* Group comparisons by Chi-squared tests
† The fourth quartile group had the highest frequency of medical visits.
‡ Group comparisons by T-tests
Table 2. Adjusted hazard ratio (aHR) of Alzheimer’s disease according to vascular risk factors *
|
Group 1
|
Group 2
|
Group 3
|
Group 4
|
Group 5
|
P for trend
|
Sex × group Interaction P
|
Total cholesterol
|
|
|
|
|
|
|
|
Ranges (mg/dL)
|
< 200
|
200 – 239
|
≥ 240
|
-
|
-
|
|
|
Total population, age- sex- aHR
|
1 [Reference]
|
1.013 (0.971-1.058)
|
1.085 (1.025-1.149)
|
-
|
-
|
0.013
|
|
Total population, aHR †
|
1 [Reference]
|
1.035 (0.991-1.082)
|
1.089 (1.025-1.156)
|
-
|
-
|
0.005
|
|
Male, aHR †
|
1 [Reference]
|
0.998 (0.924-1.079)
|
1.055 (0.929-1.198)
|
-
|
-
|
0.574
|
0.339
|
Female, aHR †
|
1 [Reference]
|
1.055 (1.000-1.114)
|
1.102 (1.028-1.181)
|
-
|
-
|
0.004
|
|
LDL cholesterol
|
|
|
|
|
|
|
|
Ranges (mg/dL)
|
< 100
|
100 – 129
|
130 – 159
|
160 – 189
|
≥ 190
|
|
|
Total population, age- sex- aHR
|
1 [Reference]
|
0.952 (0.908-0.997)
|
0.981 (0.932-1.034)
|
1.045 (0.973-1.122)
|
1.017 (0.906-1.142)
|
0.658
|
|
Total population, aHR ‡
|
1 [Reference]
|
1.006 (0.959-1.055)
|
1.046 (0.991-1.103)
|
1.116 (1.039-1.199)
|
1.085 (0.966-1.218)
|
0.004
|
|
Male, aHR ‡
|
1 [Reference]
|
0.957 (0.887-1.033)
|
0.963 (0.878-1.056)
|
1.073 (0.932-1.235)
|
1.123 (0.855-1.474)
|
0.928
|
0.208
|
Female, aHR ‡
|
1 [Reference]
|
1.044 (0.981-1.111)
|
1.096 (1.026-1.171)
|
1.150 (1.056-1.252)
|
1.095 (0.961-1.247)
|
0.0003
|
|
HDL cholesterol
|
|
|
|
|
|
|
|
Ranges (mg/dL)
|
≥ 60
|
59 – 40
|
< 40
|
-
|
-
|
|
|
Total population, age- sex- aHR
|
1 [Reference]
|
0.965 (0.924-1.008)
|
1.000 (0.940-1.062)
|
|
|
0.528
|
|
Total population, aHR §
|
1 [Reference]
|
0.945 (0.904-0.988)
|
0.941 (0.882-1.004)
|
|
|
0.019
|
|
Male, aHR §
|
1 [Reference]
|
0.953 (0.880-1.031)
|
0.978 (0.880-1.087)
|
-
|
-
|
0.517
|
0.132
|
Female, aHR §
|
1 [Reference]
|
0.943 (0.894-0.995)
|
0.913 (0.840-0.991)
|
-
|
-
|
0.012
|
|
Triglyceride
|
|
|
|
|
|
|
|
Ranges (mg/dL)
|
< 150
|
150 – 199
|
200 – 499
|
-
|
-
|
|
|
Total population, age- sex- aHR
|
1 [Reference]
|
1.031 (0.981-1.085)
|
1.101 (1.044-1.161)
|
-
|
-
|
0.0004
|
|
Total population, aHR ||
|
1 [Reference]
|
1.030 (0.978-1.084)
|
1.094 (1.034-1.156)
|
|
-
|
0.002
|
|
Male, aHR ||
|
1 [Reference]
|
1.100 (1.003-1.205)
|
1.084 (0.978-1.201)
|
-
|
-
|
0.044
|
0.189
|
Female, aHR ||
|
1 [Reference]
|
1.002 (0.941-1.067)
|
1.100 (1.030-1.176)
|
|
-
|
0.011
|
|
Fasting glucose
|
|
|
|
|
|
|
|
Ranges (mg/dL)
|
< 70
|
70 – 99
|
100 – 125
|
≥ 126
|
-
|
|
|
Total population, age- sex- aHR
|
1 [Reference]
|
0.850 (0.671-1.078)
|
0.868 (0.684-1.102)
|
1.029 (0.807-1.311)
|
-
|
<.0001
|
|
Total population, aHR #
|
1 [Reference]
|
0.897 (0.707-1.138)
|
0.882 (0.695-1.120)
|
0.896 (0.702-1.143)
|
-
|
0.689
|
|
Male, aHR #
|
1 [Reference]
|
0.839 (0.577-1.219)
|
0.825 (0.567-1.200)
|
0.907 (0.618-1.330)
|
-
|
0.358
|
0.09
|
Female, aHR #
|
1 [Reference]
|
0.932 (0.685-1.268)
|
0.918 (0.674-1.250)
|
0.891 (0.650-1.222)
|
-
|
0.27
|
|
Systolic blood pressure
|
|
|
|
|
|
|
|
Ranges (mmHg)
|
< 120
|
120 – 129
|
130 – 139
|
≥ 140
|
-
|
|
|
Total population, age- sex- aHR
|
1 [Reference]
|
0.951 (0.898-1.007)
|
0.890 (0.844-0.938)
|
0.887 (0.840-0.936)
|
-
|
<.0001
|
|
Total population, aHR **
|
1 [Reference]
|
0.925 (0.872-0.982)
|
0.854 (0.805-0.905)
|
0.827 (0.771-0.888)
|
-
|
<.0001
|
|
Male, aHR **
|
1 [Reference]
|
0.839 (0.577-1.219)
|
0.825 (0.567-1.200)
|
0.907 (0.618-1.330)
|
-
|
0.358
|
0.405
|
Female, aHR **
|
1 [Reference]
|
0.884 (0.821-0.953)
|
0.830 (0.772-0.893)
|
0.800 (0.734-0.873)
|
-
|
<.0001
|
|
Diastolic blood pressure
|
|
|
|
|
|
|
|
Ranges (mmHg)
|
< 80
|
80 – 89
|
≥ 90
|
-
|
-
|
|
|
Total population, age- sex- aHR
|
1 [Reference]
|
0.988 (0.948-1.030)
|
0.984 (0.931-1.040)
|
-
|
-
|
0.5
|
|
Total population, aHR ††
|
1 [Reference]
|
1.041 (0.996-1.089)
|
1.110 (1.037-1.188)
|
-
|
-
|
0.003
|
|
Male, aHR ††
|
1 [Reference]
|
1.035 (0.960-1.116)
|
1.018 (0.904-1.147)
|
-
|
-
|
0.565
|
0.201
|
Female, aHR ††
|
1 [Reference]
|
1.046 (0.990-1.106)
|
1.158 (1.066-1.259)
|
-
|
-
|
0.001
|
|
Body Mass Index
|
|
|
|
|
|
|
|
Ranges
|
< 18.5
|
18.5 – 24.9
|
25 – 29.9
|
30 – 34.9
|
≥ 35
|
|
|
Total population, age- sex- aHR
|
1 [Reference]
|
1.000 (0.918-1.089)
|
0.958 (0.876-1.049)
|
0.967 (0.840-1.114)
|
1.397 (0.769-2.538)
|
0.145
|
|
Total population, aHR ‡‡
|
1 [Reference]
|
0.981 (0.899-1.069)
|
0.914 (0.832-1.003)
|
0.901 (0.780-1.040)
|
1.292 (0.710-2.349)
|
0.067
|
|
Male, aHR ‡‡
|
1 [Reference]
|
1.065 (0.902-1.233)
|
1.004 (0.854-1.181)
|
1.117 (0.818-1.525)
|
2.428 (0.602-9.792)
|
0.078
|
0.536
|
Female, aHR ‡‡
|
1 [Reference]
|
0.929 (0.834-1.034)
|
0.859 (0.765-0.964)
|
0.828 (0.702-0.978)
|
1.100 (0.567-2.135)
|
0.265
|
|
* incidence was defined as events/100,000 person-years
† Adjusted for sex, age, income, life styles (smoking, alcohol consumption and exercise), co-morbidities, health care visit frequency, medication history, body mass index, systolic/diastolic blood pressure, HDL-C, triglyceride, fasting glucose, and hemoglobin. Sex was not included as a covariate in the sex subgroup analysis.
‡ Adjusted for sex, age, income, life styles (smoking, alcohol consumption and exercise), co-morbidities, health care visit frequency, medication history, body mass index, systolic/diastolic blood pressure, HDL-C, triglyceride, fasting glucose, and hemoglobin. Sex was not included as a covariate in the sex subgroup analysis.
§ Adjusted for sex, age, income, life styles (smoking, alcohol consumption and exercise), co-morbidities, health care visit frequency, medication history, body mass index, systolic/diastolic blood pressure, LDL-C, triglyceride, fasting glucose, and hemoglobin. Sex was not included as a covariate in the sex subgroup analysis.
|| Adjusted for sex, age, income, life styles (smoking, alcohol consumption and exercise), co-morbidities, health care visit frequency, medication history, body mass index, systolic/diastolic blood pressure, LDL-C, HDL-C, fasting glucose, and hemoglobin. Sex was not included as a covariate in the sex subgroup analysis.
# Adjusted for sex, age, income, life styles (smoking, alcohol consumption and exercise), co-morbidities, health care visit frequency, medication history, body mass index, systolic/diastolic blood pressure, LDL-C, HDL-C, triglyceride, and hemoglobin. Sex was not included as a covariate in the sex subgroup analysis.
** Adjusted for sex, age, income, life styles (smoking, alcohol consumption and exercise), co-morbidities, health care visit frequency, medication history, body mass index, diastolic blood pressure, LDL-C, HDL-C, triglyceride, fasting glucose, and hemoglobin. Sex was not included as a covariate in the sex subgroup analysis.
†† Adjusted for sex, age, income, life styles (smoking, alcohol consumption and exercise), co-morbidities, health care visit frequency, medication history, body mass index, systolic blood pressure, LDL-C, HDL-C, triglyceride, fasting glucose, and hemoglobin. Sex was not included as a covariate in the sex subgroup analysis.
‡‡ Adjusted for sex, age, income, life styles (smoking, alcohol consumption and exercise), co-morbidities, health care visit frequency, medication history, systolic/diastolic blood pressure, LDL-C, HDL-C, triglyceride, fasting glucose, and hemoglobin. Sex was not included as a covariate in the sex subgroup analysis.