Table 1
Demographic and clinical characteristics of the two groups:
|
Whole group
(n=1924)
|
Normal group
(n=1513)
|
Cognitive Impairment group
(n=411)
|
t/ χ 2
|
p
|
|
Age
Mean (SD)
Range
|
69.29 (5.96)
50-85
|
68.98 (5.71)
50-84
|
70.44 (6.68)
54-85
|
-4.43
|
<0.001*
|
Gender (M/F)
N (%)
|
634 (32.95)
|
472 (31.20)
|
162 (39.42)
|
9.88
|
0.002#
|
Education year
Mean (SD)
Range
|
10.09 (3.48)
0-22
|
10.23 (3.55)
0-22
|
9.55 (3.16)
0-18
|
3.514
|
0.001*
|
AD8
Mean(SD)
|
1.83 (1.75)
|
1.74 (1.67)
|
2.16 (1.98)
|
-4.43
|
<0.001*
|
MMSE
Mean (SD)
|
27.31 (2.70)
|
28.27 (1.60)
|
23.76 (2.95)
|
41.20
|
<0.001*
|
MoCA-s
Mean(SD)
|
13.91 (2.82)
|
14.47 (2.47)
|
11.84 (3.10)
|
18.02
|
<0.001*
|
PALT
Mean (SD)
|
7.30 (4.12)
|
7.89 (4.08)
|
5.14 (3.51)
|
12.46
|
<0.001*
|
DSB
Mean(SD)
|
4.46 (1.47)
|
4.64 (1.45)
|
3.78 (1.36)
|
10.75
|
<0.001*
|
DSST
Mean (SD)
|
29.53 (11.78)
|
31.05 (11.48)
|
23.96 (11.16)
|
11.34
|
<0.001*
|
CESD
Mean (SD)
|
6.94 (8.35)
|
6.65 (8.07)
|
8.00 (9.24)
|
-2.93
|
0.003*
|
APOE ε4 carrier
N
|
250(13.54)
N=1847
|
175 (12.05)
N=1452
|
75 (18.99)
N=395
|
12.76
|
<0.001#
|
AD8, Ascertain Dementia 8; MMSE, Mini-Mental State Examination; MoCA-s, Montreal Cognitive Assessment short edition; DSST, Digital Symbol Substitution Test; PALT, Paired Associative Learning Test; CESD, Center for Epidemiological Studies Depression Scale. *t test; # χ2 test.
Table 2
Logistic regression analysis of SNPs additive model stratified by the APOE ε4 allele.
|
SNP
|
MAF
|
OR(95%CI)
|
P not adjusted APOE
|
P adjusted APOE
|
P for APOE interaction
|
OR(95%CI)
|
Case
|
Control
|
DTNBP1
|
Rs1047631
|
0.013
|
0.021
|
0.719(0.371-1.394)
|
0.328
|
0.292
|
0.999
|
-
|
ABCC9
|
Rs11046205
|
0.119
|
0.139
|
0.775(0.607-0.900)
|
0.041
|
0.046
|
0.007
|
0.365(0.175-0.759)
|
SORL1
|
Rs2070045
|
0.412
|
0.450
|
0.875(0.744-1.029)
|
0.106
|
0.114
|
0.331
|
0.821(0.551-1.222)
|
TOMM40
|
Rs2075650
|
0.101
|
0.079
|
1.308(0.985-1.737)
|
0.064
|
0.789
|
0.405
|
0.784(0.441-1.392)
|
APOE promoter
|
Rs405509
|
0.302
|
0.288
|
1.078(0.905-1.284)
|
0.399
|
0.173
|
<0.001
|
2.735(1.574-4.752)
|
APOE
|
Rs429358
|
0.097
|
0.065
|
1.639(1.223-2.196)
|
0.001
|
0.453
|
-
|
-
|
CLSTN2
|
Rs6439886
|
0.062
|
0.084
|
0.732(0.531-1.009)
|
0.057
|
0.056
|
0.227
|
0.620(0.285-1.347)
|
APOE
|
Rs7412
|
0.085
|
0.082
|
1.070(0.802-1.429)
|
0.645
|
0.505
|
0.397
|
1.438(0.620-3.334)
|
MAF, minor allele frequency.
Adjusted for age, gender, education year, APOE status (except for rs429358), smoking status, alcohol drinking frequency, physical activity, hypertension, diabetes, heart disease, cerebral infarction and CESD.
Table 3
The association between APOE ε4 and cognitive impairment.
Models
|
Total sample
|
Pa
|
OR(95%CI)
|
Pb
|
OR(95%CI)
|
Pc
|
OR(95%CI)
|
APOE ε4
|
<0.001
|
1.759(1.296-2.386)
|
<0.001
|
1.752(1.290-2.378)
|
<0.001
|
1.816(1.333-2.474)
|
aAdjusted for age, gender, education year, smoking status, alcohol drinking frequency, physical activity, hypertension, diabetes, heart disease, cerebral infarction and CESD.
bAdjusted for age, gender, education year, smoking status, alcohol drinking frequency, physical activity, hypertension, diabetes, heart disease, cerebral infarction, CESD and rs11046205 additive model.
cAdjusted for age, gender, education year, smoking status, alcohol drinking frequency, physical activity, hypertension, diabetes, heart disease, cerebral infarction, CESD and rs405509 additive model.
Table 4
Multiple linear regressions of SNPs additive model and cognitive phenotype.
Gene
|
SNP
|
MMSE
|
β±se
|
PModel
|
APOE
|
rs429358
|
-0.474±0.159
|
0.003
|
Adjusted for age, gender, educational year, smoking status, alcohol drinking frequency, hypertension, diabetes, heart disease, cerebral infarction, physical status, CESD and APOE status (except for rs429358).
MMSE, Mini-Mental State Examination.
Table 5
Gene-gene interaction models identified by the GMDR method (logistic regression).
Interaction model
|
Testing accuracy (%)
|
P(CV)
|
|
|
Rs11046205, rs429358
|
54.04
|
0.0107(10/10)
|
|
Abbreviations: GMDR=general multifactor dimensionality reduction; CV=Cross-validation consistency.
Adjusted for age, gender and education year.
Table 6
Gene-lifestyle interaction models with MMSE identified by the GMDR method (linear regression).
Interaction model
|
Testing accuracy (%)
|
P(CV)
|
|
|
Rs429358, physical
|
53.98
|
0.0107(6/10)
|
|
Abbreviations: GMDR=general multifactor dimensionality reduction; CV=Cross-validation consistency.
Adjusted for age, gender and education year.