Table 1. Characteristics of the Study population.
|
Total (n=3,229)
|
Age, y
|
56.1 (5.65)
|
Education level, n (%)
|
|
<8 years
|
1304 (40.4)
|
9-12 years
|
1212 (37.5)
|
≥ 13 years
|
713 (22.1)
|
Time to follow-up visit, y
|
17.4 (1.43)
|
Follow-up AQT
|
|
Part 3 (color and form, seconds)
|
74.0 (20.2)
|
Follow-up MMSE
|
|
Total score
|
28.1 (1.81)
|
Orientation and memory scores
|
12.1 (1.02)
|
Hypertension
|
|
Hypertension, from baseline questionnaire, n (%)
|
444 (13.8)
|
Systolic blood pressure
|
139 (18.0)
|
Lipid levels
|
|
Total cholesterol
|
6.13 (1.07)
|
HDL-C
|
1.41 (0.372)
|
LDL-C
|
4.13 (0.976)
|
Triglycerides
|
1.29 (0.692)
|
Diabetes
|
|
Diabetes at baseline, n (%)
|
179 (5.5)
|
HbA1c (%)
|
4.80 (0.598)
|
Fasting glucose
|
5.01 (0.997)
|
Stroke (prevalent or incident), n (%)
|
241 (7.5)
|
Body Mass Index a
|
25.4 (3.69)
|
Smoking, n (%)
|
|
Current smoker
|
723 (22.4)
|
Former smoker
|
1137 (35.2)
|
Never smoker
|
1368 (42.4)
|
Alcohol consumption, g/day
|
10.8 (11.6)
|
Q1 (≤0.23 standard drinks/day)
|
0.61 (0.77)
|
Q2 (0.24-0.56 standard drinks/day)
|
5.15 (1.60)
|
Q3 (0.57-1.01 standard drinks/day)
|
11.01 (2.09)
|
Q4 (≥1.02 standard drinks/day)
|
26.33 (12.41)
|
APOE genotype, n (%)
|
|
ε2/ε2 or ε2/ε3
|
397 (12.3)
|
ε3/ε3
|
1780 (55.1)
|
ε2/ε4
|
79 (2.4)
|
ε3/ε4 or ε4/ε4
|
77 (2.4)
|
Physical activity (METh/week) b
|
3.41 (1.15)
|
Data are shown as mean (SD) if not otherwise specified. All data represent baseline data except for MMSE and AQT scores at follow-up. Stroke is accounted for as prevalent at baseline or incident during follow-up.
a Calculated as weight in kilograms divided by height in meters squared.
b Physical activity as metabolic equivalent hours/week (METh/week). One METh is defined as the metabolic intensity when a person is at rest. METh/week was computed by multiplying time (hours) spent on each activity by the respective metabolic equivalent task (intensity) factor (MET).
Table 2. Significant predictors of future memory function.
Baseline predictor a
|
Univariate models b
|
Basic models c
|
Multivariable model d
|
|
b (95% CI)
|
b (95% CI)
|
b (95% CI)
|
Age
|
-0.16 (-0.19 – -0.12)***
|
-0.17 (-0.20 – -0.13)***
|
-0.14
(-0.18 – -0.10)***
|
Alcohol consumption e
Q1 (≤0.23 standard drinks/day)
Q2 (0.24-0.56 standard drinks/day)
Q3 (0.57-1.01 standard drinks/day)
Q4 (≥1.02 standard drinks/day)
|
Reference
0.12 (0.02 – 0.21)*
0.15 (0.05 – 0.25)**
0.14 (0.04 – 0.23)**
|
Reference
0.06 (-0.04 – 0.17)
0.11 (0.00 – 0.21)*
0.11 (-0.00 – 0.22)
|
Reference
0.10 (-0.01 – 0.20)
0.12 (0.00– 0.23)*
0.13 (0.01 – 0.24)*
|
APOE genotype
ɛ3/ɛ3
ɛ2/ɛ2 or ɛ2/ ɛ3
ɛ2/ɛ4
ɛ3/ɛ4 or ɛ4/ɛ4
|
Reference
-0.01 (-0.12 – 0.09)
-0.02 (-0.25 – 0.20)
-0.13 (-0.21 – -0.04)**
|
Reference
0.03 (-0.08 – 0.14)
0.02 (-0.22 – 0.25)
-0.12 (-0.21 – -0.04)**
|
Reference
0.03 (-0.08 – 0.15)
0.01 (-0.23 – 0.25)
-0.14 (-0.23 – -0.05)**
|
BMI
|
-0.08 (-0.11 – -0.04)***
|
-0.04 (-0.08 – -0.00)*
|
-0.01 (-0.05 – 0.03)
|
Diabetes f
|
-0.36 (-0.51 – -0.21)***
|
-0.29 (-0.44 – -0.13)***
|
Not included g
|
Education
≤8 years
9-12 years
>12 years
|
Reference
0.25 (0.17 – 0.33)***
0.42 (0.33 – 0.51)***
|
Reference
0.21 (0.12 – 0.29)***
0.36 (0.27 – 0.46)***
|
Reference
0.17 (0.08 – 0.26)***
0.32 (0.21 – 0.42)***
|
Glucose (plasma)
|
-0.10 (-0.14 – -0.07)***
|
-0.09 (-0.12 – -0.05)***
|
Not included g
|
HbA1c
|
-0.11 (-0.14 – -0.07)***
|
-0.07 (-0.11 – -0.04)***
|
-0.08 (-0.12 – -0.04)***
|
HDL-C
|
0.09 (0.06 – 0.13)***
|
0.06 (0.02 – 0.11)**
|
0.03 (-0.02 – 0.08)
|
Sex (0=men, 1=women)
|
0.24 (0.17 – 0.31)***
|
0.24 (0.17 –0.32) ***
|
0.23 (0.14 – 0.32)***
|
Systolic blood pressure
|
-0.11 (-0.14 – -0.07)***
|
-0.04 (-0.08 – -0.00)*
|
-0.03 (-0.07 – 0.01)
|
Triglycerides
|
-0.10 (-0.14 – -0.06)***
|
-0.05 (-0.10 – -0.01)*
|
-0.01 (-0.07 – 0.04)
|
Only predictors that were significant in the basic model are shown in Table 2. The predictors that were non-significant in the basic model are shown in eTable 1 and included: Carotid stenosis, total cholesterol levels, hypertension, LDL-C, physical activity, prevalent or incident stroke and smoking. Predictors in bold represent the significant predictors from the multivariable model.
a All continuous variables used as z-scores (i.e, not alcohol, APOE, diabetes, education, hypertension and sex).
b Including only the predictor and time between baseline and follow-up.
c Including the predictor adjusted for age, sex, education, time between baseline and follow-up, and prevalent or incident stroke.
d One model combining all significant predictors from the basic models, adjusted for age, sex, education, time between baseline and follow-up, prevalent or incident stroke and blood lipid lowering medication.
e Alcohol consumption in quartiles with lowest quartile as reference: Q1 ≤0.23 standard drinks/day (0-3.37g/day); Q2 0.24-0.56 standard drinks/day (3.38- 7.83g/day); Q3 0.57-1.01 standard drinks/day (7.84-15.2g/day); Q4 ≥1.02 standard drinks/day, (≥15.3g/day).
f Defined as a diabetes diagnosis entered in the baseline questionnaire or having fasting plasma glucose levels >6mmol/L at baseline.
g To avoid collinearity issues, HbA1c, diabetes, and plasma glucose levels were not entered in the same model (only HbA1c in the multivariable model)
* p<0.05, ** p<0.01, *** p<0.001
Table 3. Significant predictors of future attention/executive function.
Baseline predictor a
|
Univariate model b
|
Basic model c
|
Multivariable model d
|
|
b (95% CI)
|
b (95% CI)
|
b (95% CI)
|
Age
|
-0.23 (-0.26 – -0.19)***
|
-0.21 (-0.24 – -0.17)***
|
-0.19 (-0.23 – -0.15)***
|
Alcohol consumption e
Q1 (≤0.23 standard drinks/day)
Q2 (0.24-0.56 standard drinks /day)
Q3 (0.57-1.01 standard drinks/day)
Q4 (≥1.02 standard drinks/day)
|
Reference
0.17 (0.08 – 0.27)***
0.23 (0.13 – 0.32)***
0.30 (0.20 – 0.40)***
|
Reference
0.15 (0.04 – 0.25)**
0.17 (0.07 – 0.28)***
0.26 (0.16 – 0.37)***
|
Reference
0.12 (0.01 – 0.23)*
0.14 (0.03 – 0.25)*
0.21 (0.10 – 0.33)**
|
BMI
|
-0.11 (-0.14 – -0.08)***
|
-0.07 (-0.11 – -0.03)***
|
-0.09 (-0.09 – -0.01)*
|
Total cholesterol
|
-0.02 (-0.06 – 0.02)
|
0.05 (0.01– 0.08)*
|
0.04 (0.00 – 0.08)*
|
Diabetes f
|
-0.44 (-0.59 – -0.29)***
|
-0.37 (-0.52 – -0.21)***
|
Not included g
|
Education
≤8 years
9-12 years
>12 years
|
Reference
0.35 (0.28 – 0.43)***
0.48 (0.39 – 0.57)***
|
Reference
0.31 (0.23 – 0.40)***
0.41 (0.31 – 0.50)***
|
Reference
0.29 (0.20 – 0.37)***
0.35 (0.25 – 0.45)***
|
Glucose (plasma)
|
-0.10 (-0.13 – -0.06) ***
|
-0.07 (-0.10 – -0.03)***
|
Not included g
|
HbA1c
|
-0.10 (-0.14 – -0.06)***
|
-0.06 (-0.10 – -0.02)***
|
-0.05 (-0.09 – -0.01)**
|
HDL-C
|
0.10 (0.06 – 0.14)***
|
0.08 (0.04 – 0.13)***
|
0.05 (0.01 – 0.10)*
|
Hypertension h
|
-0.26 (-0.36 – -0.16)***
|
-0.14 (-0.24 – -0.03)*
|
-0.10 (-0.21 – 0.01)
|
Sex (0=men, 1=women)
|
0.11 (0.04 – 0.18)**
|
0.09 (0.02 – 0.16)*
|
0.07 (-0.02 – 0.16)
|
Systolic blood pressure
|
-0.12 (-0.15 – -0.08)***
|
-0.03 (-0.07 – 0.01)
|
Not included
|
Stroke (prevalent or incident)
|
-0.54 (-0.67 – -0.41)***
|
-0.41 (-0.54 – -0.28)***
|
-0.42 (-0.56 – -0.28)***
|
Only predictors that were significant in the basic model are shown in Table 3. The predictors that were non-significant in the basic model are shown in eTable 2 and included: APOE, carotid stenosis, LDL-C, physical activity, smoking, systolic blood pressure and triglycerides. Predictors in bold represent the significant predictors from the multivariable model.
a All continuous variables are shown as z-scores, (i.e., not alcohol, diabetes, education and sex).
b Including only the predictor and time between baseline and follow-up.
c Including the predictor adjusted for age, sex, education, time between baseline and follow-up and prevalent or incident stroke.
d One model combining all significant predictors from the basic models, adjusted for age, sex, education, time between baseline, prevalent or incident stroke and follow-up and blood lipid lowering medication.
e Alcohol consumption in quartiles with lowest quartile as reference: Q1 ≤0.23 standard drinks/day (0-3.37g/day); Q2 0.24-0.56 standard drinks/day (3.38- 7.83g/day); Q3 0.57-1.01 standard drinks/day (7.84-15.2g/day); Q4 ≥1.02 standard drinks/day, (≥15.3g/day).
f Defined as a diabetes diagnosis entered in the baseline questionnaire or having fasting plasma glucose levels >6mmol/L at baseline.
g To avoid collinearity issues, HbA1c, diabetes, and plasma glucose levels were not entered in the same model (only HbA1c in the multivariable model)
h Defined as hypertension from baseline questionnaire.
* p<0.05, ** p<0.01, *** p<0.001