|
Table 1:
Serum C-reactive protein (CRP) - categorical
|
|
Notes |
The reports in this table examine categories of serum levels of C-reactive protein (CRP) in relation to AD risk. Higher levels of CRP indicate a higher degree of inflammatory response. To measure CRP, most investigations used a high-sensitivity laboratory assay, which better distinguishes among lower levels of CRP than standard assays do. Sensitivity at low CRP levels may be important, because very modest elevations in CRP (>1 mg/L) are associated with increased cardiovascular risk, which may have implications for AD risk. The strategy for categorizing CRP levels varied across the papers, with some using quantiles and others using pre-established cutpoints.
|
|
|
|
Alzheimer Disease |
Total Dementia |
|
|
Paper |
Cohort |
Study Type |
# Subjects
(% Female) |
Average Follow-up Time |
Exposure Distribution
|
# of Cases |
Effect Size |
95% CI |
P-value |
# of Cases |
Effect Size |
95% CI |
P-value |
Ethnicity |
Age at Start of Follow-up:
Mean (SD)
(Range) |
Diagnostic Assessment |
Covariates & Analysis |
Comment |
Paper |
|
Ravaglia, 2007
|
CSBA
|
Incidence study reporting hazard ratios (HRs) |
804
(53%) |
3.7 y
(detail) |
< 3.0 mg/L: 50%
> 3.0 mg/L: 50%
(detail) |
34
34
Total: 68 |
1.00
1.10
* |
Ref.
0.62-2.00
* |
Ref.
0.75
* |
50
59
Total: 109 |
1.00
1.40
* |
Ref.
0.90-2.10
* |
Ref.
0.12
* |
(detail) |
74
(6)
(
-
)
(detail) |
Screening: Informant interview, MMSE, Other
AD Diagnosis: NINCDS ADRDA
(detail) |
A, E, G, APOE4, BMI, CVD, PA, HCY, CRT, FOL, SH, VTB‡
(detail) |
|
Ravaglia, 2007
|
|
Schmidt, 2002
|
HAAS
|
Nested case control study with cumulative incidence sampling reporting odds ratios (ORs) |
1050
(0%) |
25 y
* |
< 0.34 mg/L: 24%
0.34-0.56 mg/L: 26%
0.57-1.00 mg/L: 25%
>1.00 mg/L: 25%
(detail) |
-
-
-
-
Total: 95 |
1.00
2.80
5.40
2.30 |
Ref.
1.30-6.30
2.50-11.70
1.00-5.40 |
Ref.
0.01
< 0.0001
0.05
* |
-
-
-
-
Total: 214 |
1.00
2.70
3.80
2.40 |
Ref.
1.50-4.90
1.30-4.30
1.30-4.30 |
Ref.
0.001
< 0.0001
0.004
* |
Japanese-American
(detail) |
55
(5)
(
-
) |
Screening: CASI, IQ-CODE
AD Diagnosis: Brain Imaging, CERAD, DSM IIIR, Neuropsychological examination
(detail) |
A, E, ABI, APOE4, AF, BMI, CHD, DM, DBP, FUT, LVH, SM, SH, SBP, TC‡
(detail) |
|
Schmidt, 2002
|
|
Sundelof, 2009
|
ULSAM
|
Incidence study reporting hazard ratios (HRs) |
749
(0%) |
5.3 y
(detail) |
< 1.81 mg/L: 50%
> 1.81 mg/L: 50%
(detail) |
-
-
Total: 46 |
1.00
0.77 |
Ref.
0.38-1.55 |
Ref.
0.48 |
-
-
Total: 70 |
1.00
1.21 |
Ref.
0.76-1.93 |
Ref.
0.42 |
Caucasian
(detail) |
78
(1)
(
-
)
(detail) |
Screening: MMSE, Other
AD Diagnosis: DSM IV, NINCDS ADRDA
(detail) |
A, E, AIM, APOE4, ASP, BMI, DM, HTN, SCH, SM, SH‡
(detail) |
|
Sundelof, 2009
|
|
Sundelof, 2009
|
ULSAM
|
Incidence study reporting hazard ratios (HRs) |
1062
(0%) |
11 y
(detail) |
< 1.19 mg/L: 50%
> 1.19 mg/L: 50%
(detail) |
-
-
Total: 81 |
1.00
1.23 |
Ref.
0.72-1.10 |
Ref.
0.43 |
-
-
Total: 165 |
1.00
1.21 |
Ref.
0.85-1.73 |
Ref.
0.3 |
Caucasian
(detail) |
71
(1)
(
-
)
(detail) |
Screening: MMSE, Other
AD Diagnosis: DSM IV, NINCDS ADRDA
(detail) |
A, E, AIM, APOE4, ASP, BMI, DM, HTN, SCH, SM, SH‡
(detail) |
|
Sundelof, 2009
|
|
Tan, 2007
|
Framingham Heart Study
|
Incidence study reporting hazard ratios (HRs) |
691
(62%) |
7.0 y
(detail) |
low (0 mg/L): 69%
intermediate (1-2 mg/L): 12%
high (> 3 mg/L): 19%
(detail) |
30
3
11
Total: 44 |
1.00
0.75†
1.68 |
Ref.
0.22-2.57
0.75-3.71 |
Ref.
0.65
0.21 |
|
|
|
|
(detail) |
79
(5)
(
-
) |
Screening: MMSE, Other
AD Diagnosis: Autopsy, Brain Imaging, Medical History, NINCDS ADRDA, Neurologic examination, Neuropsychological examination
(detail) |
A, E, G, APOE4, BMI, O, HCY, SM, SH‡
(detail) |
|
Tan, 2007
|
* Derived value.
† Five or fewer cases exist.
‡ Covariates: "A" (age), "E" (education), "G" (gender), "ABI" (ankle-brachial index), "AIM" (anti-inflammatory medication), "APOE4" (APOE e4 genotype), "ASP" (aspirin ), "AF" (atrial fibrillation), "BMI" (body mass index), "CVD" (cardiovascular disease), "CHD" (coronary heart disease), "DM" (diabetes mellitus), "DBP" (diastolic blood pressure), "FUT" (follow up time), "HTN" (hypertension), "LVH" (left ventricular hypertrophy), "O" (other), "PA" (physical activity), "HCY" (plasma homocysteine), "SCH" (serum cholesterol), "CRT" (serum creatinine), "FOL" (serum folate), "SM" (smoking status), "SH" (stroke history), "SBP" (systolic blood pressure), "TC" (total cholesterol), "VTB" (vitamin B12)
|
|
|
|
Table 2:
C-reactive protein (CRP) - continuous, per 5.00 mg/L increase
|
|
Notes |
The report in this table examines plasma and serum C-reactive protein (CRP) in relation to AD risk, modeled as a continuous variable. We report findings over a uniform interval of CRP (effect size per 5 mg/L increment in CRP), which required us to convert some results to fit this interval.
|
|
|
|
Alzheimer Disease |
Total Dementia |
|
|
Paper |
Cohort |
Study Type |
# Subjects
(% Female) |
Average Follow-up Time |
mg/L
Mean (SD)
(Range)
|
# of Cases |
Effect Size |
95% CI |
P-value |
# of Cases |
Effect Size |
95% CI |
P-value |
Ethnicity |
Age at Start of Follow-up:
Mean (SD)
(Range) |
Diagnostic Assessment |
Covariates & Analysis |
Comment |
Paper |
|
Engelhart, 2004
|
Rotterdam Study
|
Case-cohort study reporting odds ratios (ORs) |
727
(53%) |
-
(detail) |
-
(6)
(
-
)
(detail) |
140 |
1.08
* |
0.97-1.22
* |
0.19
* |
188 |
1.10
* |
1.00-1.22
* |
0.06
* |
(detail) |
72
(9)
(
-
) |
Screening: CAMDEX, GMS, MMSE
AD Diagnosis: Brain Imaging, NINCDS ADRDA, Neurologic examination
(detail) |
A, E, G‡
(detail) |
|
Engelhart, 2004
|
|
Sundelof, 2009
|
ULSAM
|
Incidence study reporting hazard ratios (HRs) |
749
(0%) |
5.3 y
(detail) |
4
(7)
(
-
)
(detail) |
46 |
0.90
* |
0.69-1.17
* |
0.43
* |
70 |
1.05
* |
0.89-1.25
* |
0.57
* |
Caucasian
(detail) |
78
(1)
(
-
)
(detail) |
Screening: 3MSE, Other
AD Diagnosis: DSM IV, NINCDS ADRDA
(detail) |
A, E, AIM, APOE4, ASP, BMI, DM, HTN, SCH, SM, SH‡
(detail) |
|
Sundelof, 2009
|
|
Sundelof, 2009
|
ULSAM
|
Incidence study reporting hazard ratios (HRs) |
1062
(0%) |
11 y
(detail) |
3
(5)
(
-
)
(detail) |
81 |
1.18
* |
0.89-1.56
* |
0.25
* |
165 |
1.17
* |
0.96-1.42
* |
0.12
* |
Caucasian
(detail) |
71
(1)
(
-
)
(detail) |
Screening: MMSE, Other
AD Diagnosis: DSM IV, NINCDS ADRDA
(detail) |
A, E, AIM, APOE4, ASP, BMI, DM, HTN, SCH, SM, SH‡
(detail) |
|
Sundelof, 2009
|
* Derived value.
‡ Covariates: "A" (age), "E" (education), "G" (gender), "AIM" (anti-inflammatory medication), "APOE4" (APOE e4 genotype), "ASP" (aspirin ), "BMI" (body mass index), "DM" (diabetes mellitus), "HTN" (hypertension), "SCH" (serum cholesterol), "SM" (smoking status), "SH" (stroke history)
|
|
|
|
Table 3:
Serum interleukin 6 (IL-6) - categorical
|
|
Notes |
The reports in this table examine serum levels of interleukin 6 (IL-6) in relation to AD risk. They evaluate IL-6 in categories, where higher categories of IL-6 reflect a higher degree of inflammatory response.
|
|
|
|
Alzheimer Disease |
Total Dementia |
|
|
Paper |
Cohort |
Study Type |
# Subjects
(% Female) |
Average Follow-up Time |
Exposure Distribution
|
# of Cases |
Effect Size |
95% CI |
P-value |
# of Cases |
Effect Size |
95% CI |
P-value |
Ethnicity |
Age at Start of Follow-up:
Mean (SD)
(Range) |
Diagnostic Assessment |
Covariates & Analysis |
Comment |
Paper |
|
Ravaglia, 2007
|
CSBA
|
Incidence study reporting hazard ratios (HRs) |
804
(53%) |
3.7 y
(detail) |
< 1.17 pg/mL: 50%
> 1.17 pg/mL: 50%
(detail) |
28
40
Total: 68 |
1.00
1.20
* |
Ref.
0.68-2.00
* |
Ref.
0.51
* |
45
64
Total: 109 |
1.00
1.10
* |
Ref.
0.75-1.70
* |
Ref.
0.65
* |
(detail) |
74
(6)
(
-
)
(detail) |
Screening: Informant interview, MMSE, Other
AD Diagnosis: NINCDS ADRDA
(detail) |
A, E, G, APOE4, BMI, CVD, PA, HCY, CRT, FOL, SH, VTB‡
(detail) |
|
Ravaglia, 2007
|
|
Sundelof, 2009
|
ULSAM
|
Incidence study reporting hazard ratios (HRs) |
749
(0%) |
5.3 y
(detail) |
< 3.47 pg/mL: 50%
> 3.47 pg/mL: 50%
(detail) |
-
-
Total: 46 |
1.00
0.86 |
Ref.
0.43-1.70 |
Ref.
0.66 |
-
-
Total: 70 |
1.00
1.28 |
Ref.
0.80-2.07 |
Ref.
0.3 |
Caucasian
(detail) |
78
(1)
(≤
-
)
(detail) |
Screening: MMSE, Other
AD Diagnosis: DSM IV, NINCDS ADRDA
(detail) |
A, E, AIM, APOE4, ASP, BMI, DM, HTN, SCH, SM, SH‡
(detail) |
|
Sundelof, 2009
|
|
Sundelof, 2009
|
ULSAM
|
Incidence study reporting hazard ratios (HRs) |
1062
(0%) |
11 y
(detail) |
< 3.47 pg/mL: 50%
> 3.47 pg/mL: 50%
(detail) |
-
-
Total: 81 |
1.00
1.31 |
Ref.
0.78-2.21 |
Ref.
0.31 |
-
-
Total: 165 |
1.00
1.45 |
Ref.
1.06-2.07 |
Ref.
0.04 |
Caucasian
(detail) |
71
(1)
(
-
)
(detail) |
Screening: 3MSE, Other
AD Diagnosis: DSM IV, NINCDS ADRDA
(detail) |
A, E, AIM, APOE4, ASP, BMI, DM, HTN, SCH, SM, SH‡
(detail) |
|
Sundelof, 2009
|
|
Tan, 2007
|
Framingham Heart Study
|
Incidence study reporting hazard ratios (HRs) |
540
(-) |
7.0 y
(detail) |
Lowest tertile: 36%
2nd tertile: 31%
Highest tertile: 33%
(detail) |
9
11
13
Total: 33 |
1.00
1.22
1.27 |
Ref.
0.14-3.34
0.46-3.53 |
Ref.
0.7
0.64 |
|
|
|
|
(detail) |
79
(5)
(
-
)
(detail) |
Screening: MMSE, Other
AD Diagnosis: Autopsy, Brain Imaging, Medical History, NINCDS ADRDA, Neurologic examination, Neuropsychological examination
(detail) |
A, E, G, APOE4, BMI, O, HCY, SM, SH‡ |
|
Tan, 2007
|
* Derived value.
‡ Covariates: "A" (age), "E" (education), "G" (gender), "AIM" (anti-inflammatory medication), "APOE4" (APOE e4 genotype), "ASP" (aspirin ), "BMI" (body mass index), "CVD" (cardiovascular disease), "DM" (diabetes mellitus), "HTN" (hypertension), "O" (other), "PA" (physical activity), "HCY" (plasma homocysteine), "SCH" (serum cholesterol), "CRT" (serum creatinine), "FOL" (serum folate), "SM" (smoking status), "SH" (stroke history), "VTB" (vitamin B12)
|
|
|
|
Table 4:
Plasma interleukin-6 (IL-6) - continuous, per 5.00 pg/mL increase
|
|
Notes |
The report in this table examines plasma interleukin-6 (IL-6) in relation to AD risk, modeled as a continuous variable. We report findings over a uniform interval of IL-6 (effect size per 5 mg/L increment in IL-6), which required us to convert some results to fit this interval.
|
|
|
|
Alzheimer Disease |
Total Dementia |
|
|
Paper |
Cohort |
Study Type |
# Subjects
(% Female) |
Average Follow-up Time |
pg/mL
Mean (SD)
(Range)
|
# of Cases |
Effect Size |
95% CI |
P-value |
# of Cases |
Effect Size |
95% CI |
P-value |
Ethnicity |
Age at Start of Follow-up:
Mean (SD)
(Range) |
Diagnostic Assessment |
Covariates & Analysis |
Comment |
Paper |
|
Engelhart, 2004
|
Rotterdam Study
|
Case-cohort study reporting odds ratios (ORs) |
727
(53%) |
-
(detail) |
-
(5)
(
-
)
(detail) |
140
140 |
1.30
-
* |
1.05-1.62
-
* |
0.02
-
* |
188 |
1.28
* |
1.06-1.56
* |
0.01
* |
|
72
(9)
(
-
) |
Screening: CAMDEX, GMS, MMSE
AD Diagnosis: Brain Imaging, NINCDS ADRDA, Neurologic examination
(detail) |
A, E, Gठ|
|
Engelhart, 2004
|
|
Sundelof, 2009
|
ULSAM
|
Incidence study reporting hazard ratios (HRs) |
749
(0%) |
5.3 y
(detail) |
4
(7)
(
-
)
(detail) |
46 |
0.82
* |
0.42-1.60
* |
0.56
* |
70 |
1.23
* |
0.81-1.89
* |
0.34
* |
Caucasian
(detail) |
-
(-)
(
-
)
(detail) |
Screening: MMSE, Other
AD Diagnosis: DSM IV, NINCDS ADRDA
(detail) |
A, E, AIM, APOE4, ASP, BMI, DM, HTN, SCH, SM, SH‡
(detail) |
|
Sundelof, 2009
|
|
Sundelof, 2009
|
ULSAM
|
Incidence study reporting hazard ratios (HRs) |
1062
(0%) |
11 y
(detail) |
6
(9)
(
-
)
(detail) |
81 |
1.03
* |
0.90-1.19
* |
0.68
* |
165 |
1.23
* |
1.12-1.35
* |
< 0.0001
* |
(detail) |
71
(1)
(
-
)
(detail) |
Screening: MMSE, Other
AD Diagnosis: DSM IV, NINCDS ADRDA
(detail) |
A, E, AIM, APOE4, ASP, BMI, DM, HTN, SCH, SM, SH‡
(detail) |
|
Sundelof, 2009
|
* Derived value.
‡ Covariates: "A" (age), "E" (education), "G" (gender), "AIM" (anti-inflammatory medication), "APOE4" (APOE e4 genotype), "ASP" (aspirin ), "BMI" (body mass index), "DM" (diabetes mellitus), "HTN" (hypertension), "SCH" (serum cholesterol), "SM" (smoking status), "SH" (stroke history)
§ Covariates for total dementia are different.
|
|
|
|
Table 5:
Plasma alpha-1-antichymotrypsin (ACT) - categorical
|
|
Notes |
The reports in this table examine plasma levels of alpha-1-antichymotrypsin (ACT) in relation to AD risk. They evaluate ACT in categories, where higher categories of ACT reflect a higher degree of inflammatory response.
|
|
|
|
Alzheimer Disease |
Total Dementia |
|
|
Paper |
Cohort |
Study Type |
# Subjects
(% Female) |
Average Follow-up Time |
Exposure Distribution
|
# of Cases |
Effect Size |
95% CI |
P-value |
# of Cases |
Effect Size |
95% CI |
P-value |
Ethnicity |
Age at Start of Follow-up:
Mean (SD)
(Range) |
Diagnostic Assessment |
Covariates & Analysis |
Comment |
Paper |
|
Ravaglia, 2007
|
CSBA
|
Incidence study reporting hazard ratios (HRs) |
804
(53%) |
3.7 y
(detail) |
< 369 mg/dL: 50%
> 369 mg/dL: 50%
(detail) |
29
39
Total: 68 |
1.00
1.30
* |
Ref.
0.74-2.20
* |
Ref.
0.35
* |
41
68
Total: 109 |
1.00
1.50
* |
Ref.
0.96-2.20
* |
Ref.
0.06
* |
(detail) |
74
(6)
(
-
)
(detail) |
Screening: Informant interview, MMSE, Other
AD Diagnosis: NINCDS ADRDA
(detail) |
A, E, G, APOE4, BMI, CVD, PA, HCY, CRT, FOL, SH, VTB‡
(detail) |
|
Ravaglia, 2007
|
* Derived value.
‡ Covariates: "A" (age), "E" (education), "G" (gender), "APOE4" (APOE e4 genotype), "BMI" (body mass index), "CVD" (cardiovascular disease), "PA" (physical activity), "HCY" (plasma homocysteine), "CRT" (serum creatinine), "FOL" (serum folate), "SH" (stroke history), "VTB" (vitamin B12)
|
|
|
|
Table 6:
Plasma alpha-1-antichymotrypsin (ACT) - continuous, per 15.0 mg/dL increase
|
|
Notes |
The report in this table examines plasma alpha-1-antichymotrypsin (ACT) in relation to AD risk, modeled as a continuous variable. We report findings over a uniform interval of ACT (effect size per 15 mg/dL increment in ACT), which required us to convert some results to fit this interval.
|
|
|
|
Alzheimer Disease |
Total Dementia |
|
|
Paper |
Cohort |
Study Type |
# Subjects
(% Female) |
Average Follow-up Time |
mg/dL
Mean (SD)
(Range)
|
# of Cases |
Effect Size |
95% CI |
P-value |
# of Cases |
Effect Size |
95% CI |
P-value |
Ethnicity |
Age at Start of Follow-up:
Mean (SD)
(Range) |
Diagnostic Assessment |
Covariates & Analysis |
Comment |
Paper |
|
Engelhart, 2004
|
Rotterdam Study
|
Case-cohort study reporting odds ratios (ORs) |
727
(53%) |
-
(detail) |
-
(16)
(
-
)
(detail) |
140 |
1.32
* |
1.08-1.61
* |
0.01
* |
188 |
1.45
* |
1.21-1.73
* |
< 0.0001
* |
(detail) |
72
(9)
(
-
) |
Screening: CAMDEX, GMS, MMSE
AD Diagnosis: Brain Imaging, NINCDS ADRDA, Neurologic examination
(detail) |
A, E, G‡ |
|
Engelhart, 2004
|
* Derived value.
‡ Covariates: "A" (age), "E" (education), "G" (gender)
|