Overview

1. Descriptive analyses

2. Results based on current analysis plan

3. Risk-factor analysis

4. Dementia vs. non-dementia analysis

5. Detrended analysis

6. Baseline exposure only analysis

Descriptive Analysis

Table 1

Wave 1
(N=2322)		 Wave 2
(N=739)		 Wave 3
(N=1865)		 Overall
(N=4926)
Baseline PM2.5 (5 year)
Mean (SD) 13.1 (0.832) 9.30 (0.544) 7.04 (0.996) 10.3 (2.95)
Median [Min, Max] 13.1 [10.2, 16.0] 9.29 [7.64, 10.9] 7.00 [4.72, 9.55] 9.78 [4.72, 16.0]
Missing 10 (0.4%) 1 (0.1%) 12 (0.6%) 23 (0.5%)
Baseline NO2 (5 year)
Mean (SD) 15.9 (2.99) 16.9 (3.56) 13.2 (3.13) 15.0 (3.46)
Median [Min, Max] 15.4 [4.84, 35.7] 16.3 [8.80, 34.0] 12.8 [5.15, 31.7] 14.7 [4.84, 35.7]
Missing 9 (0.4%) 0 (0%) 11 (0.6%) 20 (0.4%)
Number of Years of Followup
Mean (SD) 10.6 (6.48) 9.78 (5.46) 6.73 (3.53) 9.01 (5.68)
Median [Min, Max] 10.0 [1.00, 26.0] 10.0 [1.00, 18.0] 6.00 [1.00, 14.0] 8.00 [1.00, 26.0]
CASI Score (IRT)
Mean (SD) 0.218 (0.717) 0.268 (0.728) 0.538 (0.651) 0.346 (0.710)
Median [Min, Max] 0.230 [-2.69, 1.75] 0.271 [-1.78, 1.75] 0.596 [-1.87, 1.75] 0.384 [-2.69, 1.75]
Baseline Age
Mean (SD) 74.6 (6.06) 76.1 (6.54) 72.3 (6.04) 74.0 (6.29)
Median [Min, Max] 74.0 [65.0, 101] 75.0 [65.0, 96.0] 70.0 [65.0, 98.0] 73.0 [65.0, 101]
Gender
Female 1386 (59.7%) 433 (58.6%) 1064 (57.1%) 2883 (58.5%)
Male 936 (40.3%) 306 (41.4%) 801 (42.9%) 2043 (41.5%)
Race
Non-White 201 (8.7%) 96 (13.0%) 218 (11.7%) 515 (10.5%)
White 2121 (91.3%) 643 (87.0%) 1641 (88.0%) 4405 (89.4%)
Missing 0 (0%) 0 (0%) 6 (0.3%) 6 (0.1%)
Birth Cohort
1890-1905 164 (7.1%) 12 (1.6%) 0 (0%) 176 (3.6%)
1910 304 (13.1%) 41 (5.5%) 6 (0.3%) 351 (7.1%)
1915 555 (23.9%) 110 (14.9%) 35 (1.9%) 700 (14.2%)
1920 726 (31.3%) 164 (22.2%) 76 (4.1%) 966 (19.6%)
1925 573 (24.7%) 178 (24.1%) 143 (7.7%) 894 (18.1%)
1930 0 (0%) 213 (28.8%) 285 (15.3%) 498 (10.1%)
1935-1950 0 (0%) 21 (2.8%) 1320 (70.8%) 1341 (27.2%)
Education
Less than HS 328 (14.1%) 41 (5.5%) 33 (1.8%) 402 (8.2%)
GED/HS 1138 (49.0%) 301 (40.7%) 405 (21.7%) 1844 (37.4%)
Bachelor's 455 (19.6%) 177 (24.0%) 510 (27.3%) 1142 (23.2%)
Master's 183 (7.9%) 98 (13.3%) 498 (26.7%) 779 (15.8%)
Doctorate 72 (3.1%) 59 (8.0%) 165 (8.8%) 296 (6.0%)
Other 144 (6.2%) 63 (8.5%) 254 (13.6%) 461 (9.4%)
Missing 2 (0.1%) 0 (0%) 0 (0%) 2 (0.0%)
APOE Status
- APOE e4 1596 (68.7%) 481 (65.1%) 1089 (58.4%) 3166 (64.3%)
+ APOE e4 535 (23.0%) 169 (22.9%) 431 (23.1%) 1135 (23.0%)
Missing 191 (8.2%) 89 (12.0%) 345 (18.5%) 625 (12.7%)
Smoking Status
Never 1103 (47.5%) 363 (49.1%) 952 (51.0%) 2418 (49.1%)
Former 1066 (45.9%) 348 (47.1%) 851 (45.6%) 2265 (46.0%)
Current 153 (6.6%) 27 (3.7%) 53 (2.8%) 233 (4.7%)
Missing 0 (0%) 1 (0.1%) 9 (0.5%) 10 (0.2%)
Exercise Regularly
No 633 (27.3%) 248 (33.6%) 475 (25.5%) 1356 (27.5%)
Yes 1688 (72.7%) 491 (66.4%) 1379 (73.9%) 3558 (72.2%)
Missing 1 (0.0%) 0 (0%) 11 (0.6%) 12 (0.2%)
Hypertension
No 1440 (62.0%) 418 (56.6%) 1016 (54.5%) 2874 (58.3%)
Yes 876 (37.7%) 315 (42.6%) 822 (44.1%) 2013 (40.9%)
Missing 6 (0.3%) 6 (0.8%) 27 (1.4%) 39 (0.8%)
CHF
No 2230 (96.0%) 707 (95.7%) 1802 (96.6%) 4739 (96.2%)
Yes 89 (3.8%) 31 (4.2%) 50 (2.7%) 170 (3.5%)
Missing 3 (0.1%) 1 (0.1%) 13 (0.7%) 17 (0.3%)
Stroke
No 2255 (97.1%) 699 (94.6%) 1822 (97.7%) 4776 (97.0%)
Yes 65 (2.8%) 38 (5.1%) 32 (1.7%) 135 (2.7%)
Missing 2 (0.1%) 2 (0.3%) 11 (0.6%) 15 (0.3%)
Diabetes
No 2098 (90.4%) 659 (89.2%) 1429 (76.6%) 4186 (85.0%)
Yes 224 (9.6%) 78 (10.6%) 208 (11.2%) 510 (10.4%)
Missing 0 (0%) 2 (0.3%) 228 (12.2%) 230 (4.7%)
BMI
Mean (SD) 27.2 (4.77) 27.5 (4.90) 27.7 (5.17) 27.4 (4.95)
Median [Min, Max] 26.6 [15.7, 49.4] 26.7 [16.0, 56.8] 26.8 [16.3, 54.7] 26.7 [15.7, 56.8]
Missing 21 (0.9%) 27 (3.7%) 60 (3.2%) 108 (2.2%)
Asthma
No 2097 (90.3%) 663 (89.7%) 1414 (75.8%) 4174 (84.7%)
Yes 221 (9.5%) 75 (10.1%) 209 (11.2%) 505 (10.3%)
Missing 4 (0.2%) 1 (0.1%) 242 (13.0%) 247 (5.0%)
COPD
No 2081 (89.6%) 660 (89.3%) 1490 (79.9%) 4231 (85.9%)
Yes 229 (9.9%) 78 (10.6%) 130 (7.0%) 437 (8.9%)
Missing 12 (0.5%) 1 (0.1%) 245 (13.1%) 258 (5.2%)
Heart Disease
No 1877 (80.8%) 574 (77.7%) 1638 (87.8%) 4089 (83.0%)
Yes 438 (18.9%) 160 (21.7%) 201 (10.8%) 799 (16.2%)
Missing 7 (0.3%) 5 (0.7%) 26 (1.4%) 38 (0.8%)
Cardiovascular Disease
No 2086 (89.8%) 653 (88.4%) 1713 (91.8%) 4452 (90.4%)
Yes 227 (9.8%) 80 (10.8%) 121 (6.5%) 428 (8.7%)
Missing 9 (0.4%) 6 (0.8%) 31 (1.7%) 46 (0.9%)
Respiratory Disease
Mean (SD) 0.165 (0.371) 0.172 (0.378) 0.179 (0.383) 0.171 (0.376)
Median [Min, Max] 0 [0, 1.00] 0 [0, 1.00] 0 [0, 1.00] 0 [0, 1.00]
Missing 2 (0.1%) 0 (0%) 226 (12.1%) 228 (4.6%)
Neighborhood Median Household Income
< 20,000 10 (0.4%) 4 (0.5%) 11 (0.6%) 25 (0.5%)
20,000 - 34,999 216 (9.3%) 94 (12.7%) 173 (9.3%) 483 (9.8%)
35,000 - 49,999 771 (33.2%) 247 (33.4%) 541 (29.0%) 1559 (31.6%)
50,000 - 74,999 1122 (48.3%) 300 (40.6%) 910 (48.8%) 2332 (47.3%)
> 75,000 203 (8.7%) 94 (12.7%) 197 (10.6%) 494 (10.0%)
Missing 0 (0%) 0 (0%) 33 (1.8%) 33 (0.7%)
AD PRS Score (No APOE)
Mean (SD) -0.176 (0.339) -0.197 (0.341) -0.168 (0.329) -0.176 (0.336)
Median [Min, Max] -0.195 [-1.61, 1.37] -0.201 [-1.20, 1.45] -0.177 [-1.13, 1.16] -0.186 [-1.61, 1.45]
Missing 669 (28.8%) 238 (32.2%) 643 (34.5%) 1550 (31.5%)
AD PRS Score
Mean (SD) 0.0958 (0.640) 0.0661 (0.633) 0.190 (0.703) 0.126 (0.664)
Median [Min, Max] -0.0895 [-1.61, 2.75] -0.0752 [-1.10, 2.83] -0.0202 [-1.13, 2.79] -0.0647 [-1.61, 2.83]
Missing 669 (28.8%) 238 (32.2%) 643 (34.5%) 1550 (31.5%)
AD Inflam Score
Mean (SD) -0.124 (0.194) -0.138 (0.195) -0.123 (0.194) -0.126 (0.194)
Median [Min, Max] -0.127 [-0.793, 0.549] -0.128 [-0.783, 0.455] -0.126 [-0.688, 0.437] -0.127 [-0.793, 0.549]
Missing 669 (28.8%) 238 (32.2%) 643 (34.5%) 1550 (31.5%)



CASI Visualization


CASI Score by participant age






CASI Score by time since entry








Primary Results

Model 1 Results

Reduced Model
Cross-sectional: Entry Air Pollutant + Entry Age(linear)
Longitudinal: Air_Pollutant + Age over 85

m1 <- lmer(casi_irt ~ baseline_no2_05_yr + 
                 age_centered + 
                 time_since_entry +
                 (time_since_entry | SUBJECT) + 
                 (age85:time_since_entry) + 
                 (exp_avg_no2_05_yr:time_since_entry), 
                 data = data6, 
                 control = lmerControl(optimizer ="Nelder_Mead", optCtrl=list(maxfun=2e5)))

m1_5_tab
  Model 1, PM 2.5 Model 1, NO2
Predictors Estimates CI p Estimates CI p
(Intercept) 0.7199 0.6550 – 0.7848 <0.001 0.6400 0.5609 – 0.7191 <0.001
Baseline PM2.5 (5 year) -0.0374 -0.0435 – -0.0312 <0.001
time_since_entry:exp_avg_pm25_05_yr 0.0099 0.0088 – 0.0111 <0.001
Baseline NO2 (5 year) -0.0186 -0.0237 – -0.0135 <0.001
time_since_entry:exp_avg_no2_05_yr 0.0022 0.0017 – 0.0026 <0.001
Baseline Age (centered) -0.0443 -0.0471 – -0.0415 <0.001 -0.0448 -0.0476 – -0.0420 <0.001
Time Since Entry -0.1133 -0.1221 – -0.1044 <0.001 -0.0700 -0.0766 – -0.0633 <0.001
age85:time_since_entry -0.0167 -0.0191 – -0.0143 <0.001 -0.0216 -0.0238 – -0.0193 <0.001
Random Effects
σ2 0.23 0.23
τ00 0.28 SUBJECT 0.28 SUBJECT
τ11 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry
ρ01 -0.01 SUBJECT 0.01 SUBJECT
ICC 0.68 0.67
N 4903 SUBJECT 4906 SUBJECT
Observations 25541 25555
Marginal R2 / Conditional R2 0.202 / 0.746 0.193 / 0.732

Model 2 Results

A Priori Model
M1 +
Cross Sectional: gender + birth cohort + APOE e4 status
Longitudinal: birth cohort + APOE e4 status

m2 <- lmer(casi_irt ~ baseline_no2_05_yr + 
             age_centered +  
             birth_cohort_cat_updated + 
             apoe +
             gender +
             time_since_entry +
             (time_since_entry | SUBJECT) + 
             (age85:time_since_entry) + 
             (exp_avg_no2_05_yr:time_since_entry) + 
             (birth_cohort_cat_updated:time_since_entry) + 
             (apoe:time_since_entry), 
             data = data6, weights = sw.apoe.karl, 
             control = lmerControl(optimizer ="Nelder_Mead", optCtrl=list(maxfun=2e5)))

m2_5_tab
  Model 2, PM 2.5 Model 2, NO2
Predictors Estimates CI p Estimates CI p
(Intercept) 0.9507 0.7494 – 1.1520 <0.001 0.7414 0.6395 – 0.8433 <0.001
Baseline PM2.5 (5 year) -0.0467 -0.0633 – -0.0301 <0.001
time_since_entry:exp_avg_pm25_05_yr 0.0172 0.0159 – 0.0186 <0.001
Baseline NO2 (5 year) -0.0177 -0.0235 – -0.0119 <0.001
time_since_entry:exp_avg_no2_05_yr 0.0039 0.0034 – 0.0045 <0.001
Baseline Age (centered) -0.0454 -0.0526 – -0.0382 <0.001 -0.0371 -0.0417 – -0.0325 <0.001
Gender: Male -0.1856 -0.2216 – -0.1496 <0.001 -0.1837 -0.2199 – -0.1475 <0.001
Time Since Entry -0.1791 -0.1914 – -0.1669 <0.001 -0.1013 -0.1108 – -0.0918 <0.001
birth_cohort_cat_updated1890-1905 0.0938 -0.0593 – 0.2469 0.230 -0.0712 -0.1963 – 0.0538 0.264
Birth Cohort: 1910 0.0369 -0.0684 – 0.1421 0.492 -0.0735 -0.1625 – 0.0155 0.105
Birth Cohort: 1915 0.0354 -0.0361 – 0.1068 0.332 -0.0211 -0.0875 – 0.0453 0.533
Birth Cohort: 1925 -0.0841 -0.1506 – -0.0175 0.013 -0.0232 -0.0838 – 0.0374 0.453
Birth Cohort: 1930 -0.0917 -0.1915 – 0.0081 0.072 0.0358 -0.0353 – 0.1068 0.324
birth_cohort_cat_updated1935-1950 -0.1258 -0.2552 – 0.0036 0.057 0.0443 -0.0187 – 0.1074 0.168
APOE Status: + APOE e4 -0.0583 -0.1000 – -0.0167 0.006 -0.0629 -0.1049 – -0.0208 0.003
age85:time_since_entry -0.0023 -0.0051 – 0.0005 0.101 -0.0131 -0.0157 – -0.0106 <0.001
time_since_entry:birth_cohort_cat_updated1890-1905 -0.0712 -0.0914 – -0.0511 <0.001 -0.0477 -0.0674 – -0.0280 <0.001
time_since_entry:birth_cohort_cat_updated1910 -0.0416 -0.0550 – -0.0283 <0.001 -0.0240 -0.0369 – -0.0111 <0.001
time_since_entry:birth_cohort_cat_updated1915 -0.0244 -0.0337 – -0.0152 <0.001 -0.0157 -0.0247 – -0.0068 0.001
time_since_entry:birth_cohort_cat_updated1925 0.0206 0.0129 – 0.0284 <0.001 0.0137 0.0062 – 0.0211 <0.001
time_since_entry:birth_cohort_cat_updated1930 0.0346 0.0250 – 0.0443 <0.001 0.0209 0.0116 – 0.0302 <0.001
time_since_entry:birth_cohort_cat_updated1935-1950 0.0688 0.0599 – 0.0777 <0.001 0.0502 0.0417 – 0.0588 <0.001
time_since_entry:apoe+ APOE e4 -0.0279 -0.0341 – -0.0218 <0.001 -0.0266 -0.0326 – -0.0206 <0.001
Random Effects
σ2 0.22 0.23
τ00 0.26 SUBJECT 0.26 SUBJECT
τ11 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry
ρ01 0.10 SUBJECT 0.07 SUBJECT
ICC 0.69 0.67
N 4287 SUBJECT 4289 SUBJECT
Observations 22935 22947
Marginal R2 / Conditional R2 0.263 / 0.770 0.247 / 0.751

Model 3 Results

Extended Model
M2 +
Cross Sectional: race/ethnicity + education + neighborhood SES + ACT reported income

m3 <- lmer(casi_irt ~ baseline_no2_05_yr + 
             age_centered + gender + 
             race_cat + 
             degree_cat_simp + 
             tr_med_inc_hshld_cat + 
             birth_cohort_cat_updated + 
             apoe +
             time_since_entry +
             (time_since_entry | SUBJECT) + 
             (age85:time_since_entry) + 
             (exp_avg_no2_05_yr:time_since_entry) + 
             (birth_cohort_cat_updated:time_since_entry) + 
             (apoe:time_since_entry), 
             data = data6, weights = sw.apoe.karl,
             control = lmerControl(optimizer ="Nelder_Mead", optCtrl=list(maxfun=2e5)))

m3_5_tab
  Model 3, PM 2.5 Model 3, NO2
Predictors Estimates CI p Estimates CI p
(Intercept) 0.1801 -0.0830 – 0.4432 0.180 0.0172 -0.1933 – 0.2276 0.873
Baseline PM2.5 (5 year) -0.0326 -0.0486 – -0.0167 <0.001
time_since_entry:exp_avg_pm25_05_yr 0.0174 0.0160 – 0.0188 <0.001
Baseline NO2 (5 year) -0.0116 -0.0174 – -0.0059 <0.001
time_since_entry:exp_avg_no2_05_yr 0.0040 0.0035 – 0.0045 <0.001
Baseline Age (centered) -0.0433 -0.0502 – -0.0363 <0.001 -0.0394 -0.0439 – -0.0350 <0.001
Gender: Male -0.2225 -0.2576 – -0.1874 <0.001 -0.2214 -0.2567 – -0.1860 <0.001
Race: White 0.2464 0.1891 – 0.3037 <0.001 0.2408 0.1830 – 0.2987 <0.001
Education: GED/HS 0.3568 0.2903 – 0.4232 <0.001 0.3606 0.2939 – 0.4274 <0.001
Education: Bachelor’s 0.5714 0.5000 – 0.6428 <0.001 0.5803 0.5087 – 0.6520 <0.001
Education: Master’s 0.5971 0.5193 – 0.6750 <0.001 0.6055 0.5275 – 0.6835 <0.001
Education: Doctorate 0.7433 0.6481 – 0.8385 <0.001 0.7523 0.6567 – 0.8479 <0.001
Education: Other 0.4871 0.4029 – 0.5713 <0.001 0.4921 0.4076 – 0.5766 <0.001
Neighborhood Median
Household Income: 20,000
- 34,999 		-0.0520 -0.2125 – 0.1085 0.525 -0.0284 -0.1900 – 0.1332 0.730
Neighborhood Median
Household Income: 35,000
- 49,999 		-0.0242 -0.1834 – 0.1350 0.766 0.0010 -0.1597 – 0.1617 0.990
Neighborhood Median
Household Income: 50,000
- 74,999 		-0.0094 -0.1683 – 0.1495 0.908 0.0145 -0.1463 – 0.1753 0.860
Neighborhood Median
Household Income: >
75,000 		0.0181 -0.1451 – 0.1814 0.828 0.0504 -0.1148 – 0.2155 0.550
birth_cohort_cat_updated1890-1905 0.0978 -0.0491 – 0.2446 0.192 0.0024 -0.1179 – 0.1227 0.969
Birth Cohort: 1910 0.0394 -0.0615 – 0.1404 0.444 -0.0255 -0.1111 – 0.0602 0.560
Birth Cohort: 1915 0.0402 -0.0282 – 0.1085 0.250 0.0051 -0.0585 – 0.0686 0.876
Birth Cohort: 1925 -0.0945 -0.1581 – -0.0309 0.004 -0.0571 -0.1151 – 0.0009 0.054
Birth Cohort: 1930 -0.1250 -0.2207 – -0.0292 0.011 -0.0567 -0.1257 – 0.0123 0.107
birth_cohort_cat_updated1935-1950 -0.1745 -0.2990 – -0.0501 0.006 -0.0850 -0.1483 – -0.0218 0.008
APOE Status: + APOE e4 -0.0563 -0.0961 – -0.0164 0.006 -0.0603 -0.1006 – -0.0201 0.003
Time Since Entry -0.1801 -0.1924 – -0.1678 <0.001 -0.1017 -0.1112 – -0.0922 <0.001
age85:time_since_entry -0.0020 -0.0048 – 0.0007 0.151 -0.0130 -0.0155 – -0.0104 <0.001
time_since_entry:birth_cohort_cat_updated1890-1905 -0.0723 -0.0925 – -0.0521 <0.001 -0.0485 -0.0682 – -0.0288 <0.001
time_since_entry:birth_cohort_cat_updated1910 -0.0417 -0.0550 – -0.0283 <0.001 -0.0238 -0.0368 – -0.0109 <0.001
time_since_entry:birth_cohort_cat_updated1915 -0.0249 -0.0342 – -0.0156 <0.001 -0.0160 -0.0250 – -0.0071 <0.001
time_since_entry:birth_cohort_cat_updated1925 0.0209 0.0132 – 0.0287 <0.001 0.0140 0.0065 – 0.0214 <0.001
time_since_entry:birth_cohort_cat_updated1930 0.0351 0.0254 – 0.0449 <0.001 0.0214 0.0121 – 0.0308 <0.001
time_since_entry:birth_cohort_cat_updated1935-1950 0.0690 0.0601 – 0.0779 <0.001 0.0502 0.0416 – 0.0588 <0.001
time_since_entry:apoe+ APOE e4 -0.0281 -0.0343 – -0.0219 <0.001 -0.0268 -0.0328 – -0.0208 <0.001
Random Effects
σ2 0.22 0.23
τ00 0.22 SUBJECT 0.23 SUBJECT
τ11 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry
ρ01 0.09 SUBJECT 0.07 SUBJECT
ICC 0.67 0.65
N 4280 SUBJECT 4282 SUBJECT
Observations 22835 22847
Marginal R2 / Conditional R2 0.294 / 0.769 0.280 / 0.750

Model 4 Results

Mediation Model
M2 +
Cross Sectional: hypertension + diabetes + heart diseases + cardiovascular diseases + respiratory diseases + BMI + exercise level + cigarette smoking
Visit Specific (Uit): depression + exercise level + cigarette smoking

m4 <- lmer(casi_irt ~ 
                 baseline_no2_05_yr + 
                 age_centered +  
                 gender + 
                 birth_cohort_cat_updated + 
                 apoe +
                 hypertension + 
                 diabetes + 
                 heart_disease + 
                 cv_dis + 
                 resp_dis +
                 bmi + 
                 exercise_reg + 
                 smoke +
                 time_since_entry +
                 (time_since_entry | SUBJECT) + 
                 (age85:time_since_entry) + 
                 (exp_avg_no2_05_yr:time_since_entry) + 
                 (birth_cohort_cat_updated:time_since_entry) + 
                 (apoe:time_since_entry), 
                 data = data6, weights = sw.apoe.karl,
                 control = lmerControl(optimizer ="Nelder_Mead", optCtrl=list(maxfun=2e5)))

m4_5_tab
  Model 4, PM 2.5 Model 4, NO2
Predictors Estimates CI p Estimates CI p
(Intercept) 0.8936 0.6717 – 1.1154 <0.001 0.6033 0.4678 – 0.7388 <0.001
Baseline PM2.5 (5 year) -0.0449 -0.0619 – -0.0280 <0.001
time_since_entry:exp_avg_pm25_05_yr 0.0138 0.0123 – 0.0154 <0.001
Baseline NO2 (5 year) -0.0137 -0.0195 – -0.0079 <0.001
time_since_entry:exp_avg_no2_05_yr 0.0023 0.0017 – 0.0029 <0.001
Baseline Age (centered) -0.0427 -0.0502 – -0.0351 <0.001 -0.0330 -0.0377 – -0.0282 <0.001
Gender: Male -0.1925 -0.2294 – -0.1557 <0.001 -0.1904 -0.2274 – -0.1535 <0.001
birth_cohort_cat_updated1890-1905 0.0593 -0.0971 – 0.2157 0.457 -0.1216 -0.2469 – 0.0038 0.057
Birth Cohort: 1910 0.0083 -0.0980 – 0.1147 0.878 -0.1090 -0.1971 – -0.0208 0.015
Birth Cohort: 1915 0.0340 -0.0375 – 0.1054 0.352 -0.0282 -0.0937 – 0.0374 0.399
Birth Cohort: 1925 -0.0674 -0.1343 – -0.0006 0.048 0.0021 -0.0581 – 0.0622 0.946
Birth Cohort: 1930 -0.0967 -0.1983 – 0.0050 0.062 0.0579 -0.0133 – 0.1292 0.111
birth_cohort_cat_updated1935-1950 -0.1299 -0.2626 – 0.0028 0.055 0.0701 0.0056 – 0.1347 0.033
APOE Status: + APOE e4 -0.0691 -0.1111 – -0.0272 0.001 -0.0726 -0.1150 – -0.0302 0.001
Hypertension: Yes -0.0074 -0.0350 – 0.0201 0.596 0.0023 -0.0254 – 0.0299 0.872
Diabetes: Yes -0.0675 -0.1126 – -0.0224 0.003 -0.0685 -0.1136 – -0.0233 0.003
Heart Disease: Yes -0.0282 -0.0635 – 0.0071 0.117 -0.0243 -0.0596 – 0.0111 0.178
Cardiovascular Disease:
Yes 		-0.1390 -0.1779 – -0.1002 <0.001 -0.1374 -0.1762 – -0.0986 <0.001
Respiratory Disease 0.0017 -0.0344 – 0.0379 0.925 0.0144 -0.0217 – 0.0505 0.435
BMI 0.0007 -0.0025 – 0.0039 0.666 0.0012 -0.0020 – 0.0044 0.467
Exercise Regularly: Yes 0.0354 0.0160 – 0.0549 <0.001 0.0361 0.0165 – 0.0558 <0.001
Smoking Status: Former 0.0490 0.0123 – 0.0856 0.009 0.0468 0.0100 – 0.0836 0.013
Smoking Status: Current 0.0380 -0.0308 – 0.1067 0.279 0.0222 -0.0471 – 0.0914 0.530
Time Since Entry -0.1357 -0.1494 – -0.1221 <0.001 -0.0585 -0.0687 – -0.0482 <0.001
age85:time_since_entry -0.0006 -0.0040 – 0.0029 0.741 -0.0133 -0.0164 – -0.0102 <0.001
time_since_entry:birth_cohort_cat_updated1890-1905 -0.0345 -0.0557 – -0.0133 0.001 -0.0098 -0.0306 – 0.0109 0.354
time_since_entry:birth_cohort_cat_updated1910 -0.0209 -0.0338 – -0.0080 0.002 -0.0033 -0.0157 – 0.0092 0.606
time_since_entry:birth_cohort_cat_updated1915 -0.0118 -0.0204 – -0.0032 0.007 -0.0027 -0.0110 – 0.0056 0.526
time_since_entry:birth_cohort_cat_updated1925 0.0149 0.0078 – 0.0219 <0.001 0.0070 0.0002 – 0.0137 0.043
time_since_entry:birth_cohort_cat_updated1930 0.0308 0.0208 – 0.0408 <0.001 0.0123 0.0028 – 0.0218 0.011
time_since_entry:birth_cohort_cat_updated1935-1950 0.0471 0.0367 – 0.0575 <0.001 0.0268 0.0168 – 0.0368 <0.001
time_since_entry:apoe+ APOE e4 -0.0231 -0.0292 – -0.0170 <0.001 -0.0216 -0.0276 – -0.0157 <0.001
Random Effects
σ2 0.19 0.20
τ00 0.25 SUBJECT 0.25 SUBJECT
τ11 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry
ρ01 0.10 SUBJECT 0.07 SUBJECT
ICC 0.65 0.63
N 4125 SUBJECT 4127 SUBJECT
Observations 17823 17832
Marginal R2 / Conditional R2 0.194 / 0.715 0.182 / 0.698

Model 5 Results

Interaction Model
M2 +
Cross Sectional: pollutant exposure at baseline x APOE
Longitudinal: pollutant exposure at baseline x APOE

m5 <- lmer(casi_irt ~ 
             baseline_no2_05_yr +
             age_centered +  
             gender + 
             birth_cohort_cat_updated + 
             apoe +
             (baseline_no2_05_yr:apoe) + 
             time_since_entry + 
             (time_since_entry | SUBJECT) +
             (age85:time_since_entry) + 
             (exp_avg_no2_05_yr:time_since_entry) + 
             (birth_cohort_cat_updated:time_since_entry) + 
             (apoe:time_since_entry) + 
             (exp_avg_no2_05_yr:time_since_entry):apoe, 
            data = data6, weights = sw.apoe.karl,
            control = lmerControl(optimizer ="Nelder_Mead", optCtrl=list(maxfun=2e5)))


m5_5_tab
  Model 5, PM 2.5 Model 5, NO2
Predictors Estimates CI p Estimates CI p
(Intercept) 0.9329 0.7277 – 1.1380 <0.001 0.7754 0.6639 – 0.8869 <0.001
Baseline PM2.5 (5 year) -0.0447 -0.0618 – -0.0277 <0.001
time_since_entry:exp_avg_pm25_05_yr 0.0168 0.0153 – 0.0183 <0.001
baseline_pm25_05_yr:apoe+ APOE e4 -0.0076 -0.0219 – 0.0067 0.297
apoe+ APOE e4 :time_since_entry:exp_avg_pm25_05_yr 0.0020 -0.0005 – 0.0045 0.120
Baseline NO2 (5 year) -0.0199 -0.0264 – -0.0133 <0.001
time_since_entry:exp_avg_no2_05_yr 0.0037 0.0032 – 0.0043 <0.001
baseline_no2_05_yr:apoe+ APOE e4 0.0086 -0.0037 – 0.0208 0.169
apoe+ APOE e4 :time_since_entry:exp_avg_no2_05_yr 0.0009 -0.0001 – 0.0019 0.089
APOE Status: + APOE e4 0.0109 -0.1401 – 0.1619 0.888 -0.1972 -0.3846 – -0.0097 0.039
Baseline Age (centered) -0.0453 -0.0525 – -0.0381 <0.001 -0.0371 -0.0417 – -0.0325 <0.001
Gender: Male -0.1856 -0.2216 – -0.1496 <0.001 -0.1836 -0.2198 – -0.1474 <0.001
birth_cohort_cat_updated1890-1905 0.0922 -0.0609 – 0.2454 0.238 -0.0704 -0.1954 – 0.0546 0.270
Birth Cohort: 1910 0.0352 -0.0702 – 0.1405 0.513 -0.0723 -0.1613 – 0.0167 0.112
Birth Cohort: 1915 0.0354 -0.0361 – 0.1069 0.332 -0.0213 -0.0877 – 0.0450 0.528
Birth Cohort: 1925 -0.0836 -0.1502 – -0.0171 0.014 -0.0239 -0.0845 – 0.0366 0.438
Birth Cohort: 1930 -0.0918 -0.1916 – 0.0080 0.071 0.0353 -0.0357 – 0.1064 0.329
birth_cohort_cat_updated1935-1950 -0.1262 -0.2556 – 0.0032 0.056 0.0450 -0.0181 – 0.1081 0.162
Time Since Entry -0.1762 -0.1891 – -0.1634 <0.001 -0.0987 -0.1087 – -0.0887 <0.001
age85:time_since_entry -0.0023 -0.0050 – 0.0005 0.104 -0.0131 -0.0157 – -0.0106 <0.001
time_since_entry:birth_cohort_cat_updated1890-1905 -0.0712 -0.0913 – -0.0510 <0.001 -0.0476 -0.0673 – -0.0279 <0.001
time_since_entry:birth_cohort_cat_updated1910 -0.0415 -0.0549 – -0.0282 <0.001 -0.0239 -0.0369 – -0.0110 <0.001
time_since_entry:birth_cohort_cat_updated1915 -0.0245 -0.0338 – -0.0153 <0.001 -0.0159 -0.0249 – -0.0070 <0.001
time_since_entry:birth_cohort_cat_updated1925 0.0206 0.0129 – 0.0284 <0.001 0.0136 0.0062 – 0.0210 <0.001
time_since_entry:birth_cohort_cat_updated1930 0.0348 0.0251 – 0.0445 <0.001 0.0208 0.0115 – 0.0302 <0.001
time_since_entry:birth_cohort_cat_updated1935-1950 0.0690 0.0602 – 0.0779 <0.001 0.0503 0.0418 – 0.0589 <0.001
apoe+ APOE e4 :time_since_entry -0.0413 -0.0592 – -0.0234 <0.001 -0.0376 -0.0517 – -0.0236 <0.001
Random Effects
σ2 0.22 0.23
τ00 0.26 SUBJECT 0.26 SUBJECT
τ11 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry
ρ01 0.10 SUBJECT 0.07 SUBJECT
ICC 0.69 0.67
N 4287 SUBJECT 4289 SUBJECT
Observations 22935 22947
Marginal R2 / Conditional R2 0.263 / 0.771 0.248 / 0.751

Model 6 Results

Co-Pollutant Model
M2 +
Cross Sectional: co-pollutant exposure at baseline
Longitudinal: co-pollutant

m6 <- lmer(casi_irt ~ 
                 baseline_no2_05_yr +
               (baseline_no2_05_yr:baseline_pm25_05_yr) +
                 age_centered +  
                 gender + 
                 birth_cohort_cat_updated + 
                 apoe +
                 time_since_entry +
                 (time_since_entry | SUBJECT) + 
                 (age85:time_since_entry) + 
                 (exp_avg_no2_05_yr:time_since_entry) + 
                 (birth_cohort_cat_updated:time_since_entry) + 
                 (apoe:time_since_entry) + 
                 (exp_avg_no2_05_yr:exp_avg_pm25_05_yr:time_since_entry),
                data = data6, weights = sw.apoe.karl,
                control = lmerControl(optimizer ="Nelder_Mead", optCtrl=list(maxfun=2e5)))

m6_5_tab
  Model 6, PM 2.5 Model 6, NO2
Predictors Estimates CI p Estimates CI p
(Intercept) 0.8884 0.6822 – 1.0947 <0.001 0.6765 0.5750 – 0.7780 <0.001
Baseline PM2.5 (5 year) -0.0301 -0.0510 – -0.0092 0.005
time_since_entry:exp_avg_pm25_05_yr 0.0190 0.0161 – 0.0218 <0.001
baseline_pm25_05_yr:baseline_no2_05_yr -0.0007 -0.0013 – -0.0002 0.011
time_since_entry:exp_avg_pm25_05_yr:exp_avg_no2_05_yr -0.0001 -0.0002 – 0.0000 0.177
Baseline NO2 (5 year) 0.0099 -0.0029 – 0.0227 0.130
time_since_entry:exp_avg_no2_05_yr -0.0067 -0.0080 – -0.0053 <0.001
baseline_no2_05_yr:baseline_pm25_05_yr -0.0023 -0.0033 – -0.0013 <0.001
time_since_entry:exp_avg_no2_05_yr:exp_avg_pm25_05_yr 0.0010 0.0009 – 0.0011 <0.001
Baseline Age (centered) -0.0437 -0.0510 – -0.0364 <0.001 -0.0425 -0.0491 – -0.0359 <0.001
Gender: Male -0.1861 -0.2221 – -0.1501 <0.001 -0.1859 -0.2220 – -0.1499 <0.001
birth_cohort_cat_updated1890-1905 0.0722 -0.0815 – 0.2259 0.357 0.0531 -0.0937 – 0.1999 0.478
Birth Cohort: 1910 0.0223 -0.0834 – 0.1279 0.680 0.0098 -0.0918 – 0.1113 0.851
Birth Cohort: 1915 0.0290 -0.0426 – 0.1005 0.428 0.0193 -0.0509 – 0.0895 0.590
Birth Cohort: 1925 -0.0746 -0.1414 – -0.0079 0.028 -0.0618 -0.1267 – 0.0030 0.062
Birth Cohort: 1930 -0.0701 -0.1709 – 0.0306 0.173 -0.0454 -0.1388 – 0.0479 0.340
birth_cohort_cat_updated1935-1950 -0.1025 -0.2327 – 0.0277 0.123 -0.0703 -0.1782 – 0.0377 0.202
APOE Status: + APOE e4 -0.0579 -0.0995 – -0.0164 0.006 -0.0594 -0.1011 – -0.0178 0.005
Time Since Entry -0.1852 -0.2002 – -0.1701 <0.001 -0.0631 -0.0738 – -0.0524 <0.001
age85:time_since_entry -0.0022 -0.0050 – 0.0005 0.112 -0.0058 -0.0084 – -0.0031 <0.001
time_since_entry:birth_cohort_cat_updated1890-1905 -0.0714 -0.0916 – -0.0513 <0.001 -0.0683 -0.0884 – -0.0483 <0.001
time_since_entry:birth_cohort_cat_updated1910 -0.0416 -0.0549 – -0.0282 <0.001 -0.0394 -0.0527 – -0.0261 <0.001
time_since_entry:birth_cohort_cat_updated1915 -0.0244 -0.0336 – -0.0151 <0.001 -0.0227 -0.0318 – -0.0135 <0.001
time_since_entry:birth_cohort_cat_updated1925 0.0206 0.0129 – 0.0283 <0.001 0.0183 0.0106 – 0.0259 <0.001
time_since_entry:birth_cohort_cat_updated1930 0.0346 0.0249 – 0.0443 <0.001 0.0295 0.0199 – 0.0390 <0.001
time_since_entry:birth_cohort_cat_updated1935-1950 0.0687 0.0598 – 0.0776 <0.001 0.0606 0.0518 – 0.0693 <0.001
time_since_entry:apoe+ APOE e4 -0.0280 -0.0342 – -0.0218 <0.001 -0.0277 -0.0338 – -0.0216 <0.001
Random Effects
σ2 0.22 0.22
τ00 0.26 SUBJECT 0.26 SUBJECT
τ11 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry
ρ01 0.10 SUBJECT 0.10 SUBJECT
ICC 0.69 0.68
N 4286 SUBJECT 4286 SUBJECT
Observations 22932 22932
Marginal R2 / Conditional R2 0.263 / 0.770 0.260 / 0.766





Risk Factor Analysis



The purpose of this analysis is to create simplified, minimally adjusted versions of the models to identify the association between a specific risk factor and cognition, one predictor at a time. We want to ensure that the associations between these predictors and the outcome are as we would expect them to be. If any predictors do not have the associations that we would predict, this may be a sign that there is an issue with the models.

Risk Factor Model: APOE

minimal_model_apoe <- lmer(casi_irt ~  
                             (time_since_entry | SUBJECT) + 
                             time_since_entry + 
                             age_centered + 
                             gender + 
                             race_cat + 
                             (apoe:time_since_entry) + 
                             apoe, 
                           data = data6, control = lmerControl(optimizer ="Nelder_Mead", optCtrl=list(maxfun=2e5)), weights = sw.apoe.karl)

min_model_apoe_tab
  CASI Score (IRT)
Predictors Estimates CI p
(Intercept) 0.2546 0.1939 – 0.3153 <0.001
APOE Status: + APOE e4 -0.0772 -0.1198 – -0.0346 <0.001
time_since_entry:apoe+ APOE e4 -0.0203 -0.0260 – -0.0146 <0.001
Time Since Entry -0.0492 -0.0521 – -0.0464 <0.001
Baseline Age (centered) -0.0517 -0.0545 – -0.0488 <0.001
Gender: Male -0.1798 -0.2160 – -0.1436 <0.001
Race: White 0.2735 0.2132 – 0.3338 <0.001
Random Effects
σ2 0.24
τ00 SUBJECT 0.27
τ11 SUBJECT.time_since_entry 0.00
ρ01 SUBJECT 0.03
ICC 0.63
N SUBJECT 4297
Observations 23062
Marginal R2 / Conditional R2 0.187 / 0.702


Risk Factor Model: Education

minimal_model_edu <- lmer(casi_irt ~  (time_since_entry | SUBJECT) + 
                            time_since_entry + 
                            age_centered + 
                            gender + 
                            race_cat + 
                            (degree_cat_simp:time_since_entry) +
                            degree_cat_simp, 
                          data = data6, control = lmerControl(optimizer ="Nelder_Mead", optCtrl=list(maxfun=2e5)))

min_model_edu_tab
  CASI Score (IRT)
Predictors Estimates CI p
(Intercept) -0.2380 -0.3133 – -0.1627 <0.001
Less than HS Reference
GED/HS 0.3990 0.3333 – 0.4647 <0.001
Bachelor’s 0.5915 0.5220 – 0.6609 <0.001
Master’s 0.6210 0.5470 – 0.6951 <0.001
Doctorate 0.7422 0.6500 – 0.8343 <0.001
Other 0.5157 0.4339 – 0.5976 <0.001
time_since_entry:degree_cat_simpGED/HS -0.0113 -0.0209 – -0.0018 0.020
time_since_entry:degree_cat_simpBachelor’s 0.0020 -0.0080 – 0.0120 0.699
time_since_entry:degree_cat_simpMaster’s 0.0081 -0.0026 – 0.0189 0.138
time_since_entry:degree_cat_simpDoctorate 0.0188 0.0057 – 0.0319 0.005
time_since_entry:degree_cat_simpOther 0.0007 -0.0113 – 0.0127 0.909
Time Since Entry -0.0529 -0.0617 – -0.0441 <0.001
Baseline Age (centered) -0.0451 -0.0478 – -0.0425 <0.001
Female Reference
Male -0.2115 -0.2449 – -0.1782 <0.001
Non-White Reference
White 0.2748 0.2223 – 0.3273 <0.001
Random Effects
σ2 0.24
τ00 SUBJECT 0.24
τ11 SUBJECT.time_since_entry 0.00
ρ01 SUBJECT 0.02
ICC 0.61
N SUBJECT 4918
Observations 25686
Marginal R2 / Conditional R2 0.237 / 0.705


Risk Factor Model: Polygenic Risk Scores

minimal_model_prs <- lmer(casi_irt ~  (time_since_entry | SUBJECT) + 
                            time_since_entry + 
                            age_centered + 
                            gender + 
                            race_cat + 
                            (ad_prs_withapoe:time_since_entry) + 
                            ad_prs_withapoe, 
                          data = data6, control = lmerControl(optimizer ="Nelder_Mead", optCtrl=list(maxfun=2e5)))

min_model_prs_tab
  CASI Score (IRT)
Predictors Estimates CI p
(Intercept) 0.6986 0.4413 – 0.9558 <0.001
AD PRS Score -0.0417 -0.0733 – -0.0101 0.010
time_since_entry:ad_prs_withapoe -0.0142 -0.0185 – -0.0099 <0.001
Time Since Entry -0.0525 -0.0553 – -0.0498 <0.001
Baseline Age (centered) -0.0527 -0.0559 – -0.0496 <0.001
Gender: Male -0.1921 -0.2320 – -0.1523 <0.001
Race: White -0.1579 -0.4151 – 0.0993 0.229
Random Effects
σ2 0.25
τ00 SUBJECT 0.26
τ11 SUBJECT.time_since_entry 0.00
ρ01 SUBJECT -0.01
ICC 0.61
N SUBJECT 3374
Observations 18427
Marginal R2 / Conditional R2 0.190 / 0.688


Risk Factor Model: SES

minimal_model_ses <- lmer(casi_irt ~  (time_since_entry | SUBJECT) + 
                            time_since_entry + 
                            age_centered + 
                            gender + 
                            race_cat + 
                            (tr_med_inc_hshld_cat:time_since_entry) + 
                            tr_med_inc_hshld_cat, 
                          data = data6, control = lmerControl(optimizer ="Nelder_Mead", optCtrl=list(maxfun=2e5)))

min_model_ses_tab
  CASI Score (IRT)
Predictors Estimates CI p
(Intercept) 0.300793 0.092212 – 0.509374 0.005
< 20,000 Reference
20,000 - 34,999 -0.099458 -0.306667 – 0.107750 0.347
35,000 - 49,999 -0.107379 -0.311494 – 0.096737 0.302
50,000 - 74,999 -0.121725 -0.325596 – 0.082146 0.242
75,000
-0.070616 -0.279113 – 0.137881 0.507
time_since_entry:tr_med_inc_hshld_cat20,000 - 34,999 0.013362 -0.011172 – 0.037897 0.286
time_since_entry:tr_med_inc_hshld_cat35,000 - 49,999 0.015529 -0.008650 – 0.039707 0.208
time_since_entry:tr_med_inc_hshld_cat50,000 - 74,999 0.025493 0.001364 – 0.049622 0.038
time_since_entry:tr_med_inc_hshld_cat> 75,000 0.027688 0.002879 – 0.052496 0.029
Time Since Entry -0.075281 -0.099292 – -0.051270 <0.001
Baseline Age (centered) -0.051338 -0.054048 – -0.048628 <0.001
Female Reference
Male -0.175369 -0.209638 – -0.141099 <0.001
Non-White Reference
White 0.302854 0.247585 – 0.358123 <0.001
Random Effects
σ2 0.24
τ00 SUBJECT 0.27
τ11 SUBJECT.time_since_entry 0.00
ρ01 SUBJECT 0.01
ICC 0.64
N SUBJECT 4915
Observations 25571
Marginal R2 / Conditional R2 0.184 / 0.703


Risk Factor Model: Smoking

minimal_model_smoke <- lmer(casi_irt ~  (time_since_entry | SUBJECT) + 
                              time_since_entry + 
                              age_centered + 
                              gender + 
                              race_cat + 
                              (smoke:time_since_entry) + 
                              smoke, 
                            data = data6, control = lmerControl(optimizer ="Nelder_Mead", optCtrl=list(maxfun=2e5)))

min_model_smoke_tab
  CASI Score (IRT)
Predictors Estimates CI p
(Intercept) 0.1795 0.1240 – 0.2350 <0.001
Never Reference
Former 0.0205 -0.0155 – 0.0565 0.265
Current -0.0550 -0.1287 – 0.0188 0.144
time_since_entry:smokeCurrent 0.0080 -0.0042 – 0.0202 0.197
time_since_entry:smokeFormer 0.0000 -0.0046 – 0.0047 0.987
Time Since Entry -0.0477 -0.0509 – -0.0444 <0.001
Baseline Age (centered) -0.0504 -0.0531 – -0.0477 <0.001
Female Reference
Male -0.1768 -0.2112 – -0.1424 <0.001
Non-White Reference
White 0.2987 0.2440 – 0.3533 <0.001
Random Effects
σ2 0.23
τ00 SUBJECT 0.27
τ11 SUBJECT.time_since_entry 0.00
ρ01 SUBJECT -0.00
ICC 0.63
N SUBJECT 4910
Observations 24594
Marginal R2 / Conditional R2 0.173 / 0.692


Risk Factor Model: Air Pollution

minimal_model_ap <- lmer(casi_irt ~  (time_since_entry | SUBJECT) + 
                           time_since_entry + 
                           age_centered + 
                           gender + 
                           race_cat + 
                           (exp_avg_pm25_05_yr:time_since_entry) + 
                           baseline_pm25_05_yr, 
                         data = data6, control = lmerControl(optimizer ="Nelder_Mead", optCtrl=list(maxfun=2e5)))

min_model_ap_tab
  PM 2.5 NO2
Predictors Estimates CI p Estimates CI p
(Intercept) 0.5692 0.4896 – 0.6488 <0.001 0.4770 0.3798 – 0.5741 <0.001
Baseline PM2.5 (5 year) -0.0429 -0.0489 – -0.0369 <0.001
time_since_entry:exp_avg_pm25_05_yr 0.0139 0.0129 – 0.0149 <0.001
Baseline NO2 (5 year) -0.0194 -0.0244 – -0.0143 <0.001
time_since_entry:exp_avg_no2_05_yr 0.0038 0.0033 – 0.0042 <0.001
Time Since Entry -0.1501 -0.1575 – -0.1427 <0.001 -0.1024 -0.1083 – -0.0965 <0.001
Baseline Age (centered) -0.0477 -0.0504 – -0.0450 <0.001 -0.0494 -0.0521 – -0.0466 <0.001
Gender: Male -0.1763 -0.2101 – -0.1425 <0.001 -0.1731 -0.2072 – -0.1390 <0.001
Race: White 0.3110 0.2566 – 0.3653 <0.001 0.2891 0.2341 – 0.3441 <0.001
Random Effects
σ2 0.23 0.23
τ00 0.26 SUBJECT 0.27 SUBJECT
τ11 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry
ρ01 -0.01 SUBJECT -0.00 SUBJECT
ICC 0.68 0.67
N 4897 SUBJECT 4900 SUBJECT
Observations 25510 25524
Marginal R2 / Conditional R2 0.201 / 0.747 0.185 / 0.728




Dementia vs. Non-dementia analysis



The plot below depicts the cognitive trajectories for participants up until they are censored from the study (at time 0 on the far right). Each line represents the trajectories for groups of individuals based on their reason for being censored. They key takeaway from this figure is that the cognition of those who are censored due to a dementia diagnosis have a significant drop in CASI score before censoring. This pattern makes sense as a drop in cognition would prompt an investigation into a possible dementia diagnosis, but it shows how much of the drop in CASI score that we observe is tied to the drop in cognition from soon-to-be demented individuals.


Identifying the effect of aging


The table below shows the effect of 1 year of aging (with only time as a predictor and in minimally adjusted models) using datasets where all participants are included and where patients who develop dementia are removed from the analysis. This table shows that the effect of 1 year of aging is essentially cut in half when only looking at data for those who do not develop dementia.
  All Data All Data Incident Dementia Removed Incident Dementia Removed
Predictors Estimates CI p Estimates CI p Estimates CI p Estimates CI p
(Intercept) 0.4499 0.4304 – 0.4695 <0.001 0.4633 0.4404 – 0.4861 <0.001 0.5283 0.5080 – 0.5486 <0.001 0.5229 0.4983 – 0.5474 <0.001
Time Since Entry -0.0569 -0.0593 – -0.0545 <0.001 -0.0546 -0.0570 – -0.0522 <0.001 -0.0265 -0.0286 – -0.0244 <0.001 -0.0265 -0.0286 – -0.0244 <0.001
Baseline Age (centered) -0.0507 -0.0534 – -0.0480 <0.001 -0.0408 -0.0437 – -0.0380 <0.001
Gender: Male -0.1709 -0.2055 – -0.1364 <0.001 -0.1611 -0.1962 – -0.1260 <0.001
Random Effects
σ2 0.24 0.24 0.19 0.19
τ00 0.37 SUBJECT 0.28 SUBJECT 0.29 SUBJECT 0.23 SUBJECT
τ11 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry
ρ01 0.18 SUBJECT 0.02 SUBJECT -0.05 SUBJECT -0.13 SUBJECT
ICC 0.71 0.64 0.64 0.58
N 4926 SUBJECT 4926 SUBJECT 3593 SUBJECT 3593 SUBJECT
Observations 25728 25728 18426 18426
Marginal R2 / Conditional R2 0.098 / 0.736 0.172 / 0.702 0.036 / 0.649 0.127 / 0.633



Model results with and without incident dementia

  PM2.5 PM2.5, Dementia Removed NO2 NO2, Dementia Removed
Predictors Estimates CI p Estimates CI p Estimates CI p Estimates CI p
(Intercept) 0.9507 0.7494 – 1.1520 <0.001 1.0195 0.8101 – 1.2289 <0.001 0.7414 0.6395 – 0.8433 <0.001 0.7833 0.6763 – 0.8903 <0.001
Baseline PM2.5 (5 year) -0.0467 -0.0633 – -0.0301 <0.001 -0.0484 -0.0655 – -0.0313 <0.001
time_since_entry:exp_avg_pm25_05_yr 0.0172 0.0159 – 0.0186 <0.001 0.0112 0.0098 – 0.0127 <0.001
Baseline NO2 (5 year) -0.0177 -0.0235 – -0.0119 <0.001 -0.0186 -0.0245 – -0.0126 <0.001
time_since_entry:exp_avg_no2_05_yr 0.0039 0.0034 – 0.0045 <0.001 0.0025 0.0020 – 0.0030 <0.001
Baseline Age (centered) -0.0454 -0.0526 – -0.0382 <0.001 -0.0401 -0.0473 – -0.0329 <0.001 -0.0371 -0.0417 – -0.0325 <0.001 -0.0302 -0.0350 – -0.0253 <0.001
Gender: Male -0.1856 -0.2216 – -0.1496 <0.001 -0.1672 -0.2043 – -0.1301 <0.001 -0.1837 -0.2199 – -0.1475 <0.001 -0.1661 -0.2032 – -0.1290 <0.001
Time Since Entry -0.1791 -0.1914 – -0.1669 <0.001 -0.1040 -0.1166 – -0.0915 <0.001 -0.1013 -0.1108 – -0.0918 <0.001 -0.0534 -0.0625 – -0.0442 <0.001
birth_cohort_cat_updated1890-1905 0.0938 -0.0593 – 0.2469 0.230 0.1201 -0.0431 – 0.2833 0.149 -0.0712 -0.1963 – 0.0538 0.264 -0.0591 -0.1979 – 0.0797 0.404
Birth Cohort: 1910 0.0369 -0.0684 – 0.1421 0.492 0.0363 -0.0804 – 0.1531 0.542 -0.0735 -0.1625 – 0.0155 0.105 -0.0781 -0.1820 – 0.0257 0.140
Birth Cohort: 1915 0.0354 -0.0361 – 0.1068 0.332 0.0597 -0.0212 – 0.1406 0.148 -0.0211 -0.0875 – 0.0453 0.533 -0.0002 -0.0764 – 0.0761 0.997
Birth Cohort: 1925 -0.0841 -0.1506 – -0.0175 0.013 -0.0560 -0.1294 – 0.0175 0.135 -0.0232 -0.0838 – 0.0374 0.453 0.0114 -0.0564 – 0.0791 0.742
Birth Cohort: 1930 -0.0917 -0.1915 – 0.0081 0.072 -0.0707 -0.1754 – 0.0339 0.185 0.0358 -0.0353 – 0.1068 0.324 0.0827 0.0071 – 0.1583 0.032
birth_cohort_cat_updated1935-1950 -0.1258 -0.2552 – 0.0036 0.057 -0.1505 -0.2843 – -0.0168 0.027 0.0443 -0.0187 – 0.1074 0.168 0.0536 -0.0129 – 0.1202 0.114
APOE Status: + APOE e4 -0.0583 -0.1000 – -0.0167 0.006 0.0045 -0.0415 – 0.0506 0.847 -0.0629 -0.1049 – -0.0208 0.003 0.0053 -0.0411 – 0.0517 0.823
age85:time_since_entry -0.0023 -0.0051 – 0.0005 0.101 -0.0007 -0.0037 – 0.0023 0.645 -0.0131 -0.0157 – -0.0106 <0.001 -0.0079 -0.0106 – -0.0052 <0.001
time_since_entry:birth_cohort_cat_updated1890-1905 -0.0712 -0.0914 – -0.0511 <0.001 -0.0432 -0.0623 – -0.0240 <0.001 -0.0477 -0.0674 – -0.0280 <0.001 -0.0286 -0.0476 – -0.0097 0.003
time_since_entry:birth_cohort_cat_updated1910 -0.0416 -0.0550 – -0.0283 <0.001 -0.0230 -0.0365 – -0.0095 0.001 -0.0240 -0.0369 – -0.0111 <0.001 -0.0123 -0.0257 – 0.0010 0.069
time_since_entry:birth_cohort_cat_updated1915 -0.0244 -0.0337 – -0.0152 <0.001 -0.0122 -0.0207 – -0.0037 0.005 -0.0157 -0.0247 – -0.0068 0.001 -0.0067 -0.0151 – 0.0016 0.115
time_since_entry:birth_cohort_cat_updated1925 0.0206 0.0129 – 0.0284 <0.001 0.0090 0.0024 – 0.0156 0.008 0.0137 0.0062 – 0.0211 <0.001 0.0047 -0.0018 – 0.0112 0.153
time_since_entry:birth_cohort_cat_updated1930 0.0346 0.0250 – 0.0443 <0.001 0.0148 0.0067 – 0.0228 <0.001 0.0209 0.0116 – 0.0302 <0.001 0.0065 -0.0013 – 0.0144 0.102
time_since_entry:birth_cohort_cat_updated1935-1950 0.0688 0.0599 – 0.0777 <0.001 0.0313 0.0236 – 0.0389 <0.001 0.0502 0.0417 – 0.0588 <0.001 0.0203 0.0128 – 0.0277 <0.001
time_since_entry:apoe+ APOE e4 -0.0279 -0.0341 – -0.0218 <0.001 -0.0129 -0.0183 – -0.0075 <0.001 -0.0266 -0.0326 – -0.0206 <0.001 -0.0129 -0.0183 – -0.0076 <0.001
Random Effects
σ2 0.22 0.19 0.23 0.19
τ00 0.26 SUBJECT 0.22 SUBJECT 0.26 SUBJECT 0.22 SUBJECT
τ11 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry
ρ01 0.10 SUBJECT -0.03 SUBJECT 0.07 SUBJECT -0.07 SUBJECT
ICC 0.69 0.59 0.67 0.58
N 4287 SUBJECT 3099 SUBJECT 4289 SUBJECT 3100 SUBJECT
Observations 22935 16291 22947 16297
Marginal R2 / Conditional R2 0.263 / 0.770 0.172 / 0.663 0.247 / 0.751 0.165 / 0.653



Detrended Analysis

Understanding the detreneded exposures with the effects package



The following figures were generated using the “effects” package in R. The purpose of this package is to visualize the effect of single predictor on an outcome from a linear regression model, adjusting for the effects of other predictors in the same model. The plot below serves as an example of how this package can be used. The visualization shows the effect of baseline NO2 exposure on CASI IRT taken from model 2, the a prioi model.



The following two plots display the effect of the interaction between time-varying NO2 exposure and CASI IRT score also taken from model 2. The only difference between the two is that the second figures uses the detrended NO2 exposures as opposed to the raw exposures. Each line represents the effect of NO2 on CASI IRT for the subset of data at each visit number. Notice how the lines have positive slopes in the first figure and flat/slightly negative slopes in the second figure.



The following two plots display the effect of the interaction between time-varying PM2.5 exposure and CASI IRT score also taken from model 2. Again, the first figures uses raw exposure values and the second plot uses detrended exposure values.

Detrended Models


  Model 2, PM 2.5 Model 2, NO2
Predictors Estimates CI p Estimates CI p
(Intercept) 0.4764 0.4316 – 0.5213 <0.001 0.4767 0.4319 – 0.5216 <0.001
Baseline PM2.5 Exposure
(5 year, detrended) 		-0.0387 -0.0719 – -0.0055 0.022
time_since_entry:pm25_loess_detrended -0.0077 -0.0114 – -0.0039 <0.001
Baseline NO2 Exposure (5
year, detrended) 		-0.0084 -0.0146 – -0.0022 0.008
time_since_entry:no2_loess_detrended -0.0002 -0.0008 – 0.0005 0.565
Baseline Age (centered) -0.0370 -0.0416 – -0.0323 <0.001 -0.0372 -0.0419 – -0.0326 <0.001
Gender: Male -0.1869 -0.2233 – -0.1505 <0.001 -0.1835 -0.2198 – -0.1471 <0.001
Time Since Entry -0.0427 -0.0482 – -0.0372 <0.001 -0.0426 -0.0481 – -0.0371 <0.001
birth_cohort_cat_updated1890-1905 -0.0888 -0.2143 – 0.0366 0.165 -0.0849 -0.2104 – 0.0405 0.185
Birth Cohort: 1910 -0.0907 -0.1800 – -0.0014 0.047 -0.0894 -0.1787 – -0.0000 0.050
Birth Cohort: 1915 -0.0396 -0.1062 – 0.0271 0.244 -0.0359 -0.1026 – 0.0307 0.290
Birth Cohort: 1925 -0.0092 -0.0700 – 0.0516 0.767 -0.0103 -0.0711 – 0.0505 0.740
Birth Cohort: 1930 0.0496 -0.0217 – 0.1210 0.173 0.0471 -0.0241 – 0.1184 0.195
birth_cohort_cat_updated1935-1950 0.0940 0.0336 – 0.1544 0.002 0.0918 0.0314 – 0.1522 0.003
APOE Status: + APOE e4 -0.0666 -0.1089 – -0.0243 0.002 -0.0671 -0.1094 – -0.0248 0.002
age85:time_since_entry -0.0216 -0.0239 – -0.0193 <0.001 -0.0215 -0.0238 – -0.0192 <0.001
time_since_entry:birth_cohort_cat_updated1890-1905 -0.0352 -0.0545 – -0.0159 <0.001 -0.0354 -0.0547 – -0.0162 <0.001
time_since_entry:birth_cohort_cat_updated1910 -0.0114 -0.0239 – 0.0011 0.074 -0.0120 -0.0245 – 0.0005 0.059
time_since_entry:birth_cohort_cat_updated1915 -0.0081 -0.0167 – 0.0005 0.066 -0.0083 -0.0168 – 0.0003 0.059
time_since_entry:birth_cohort_cat_updated1925 0.0079 0.0008 – 0.0150 0.030 0.0079 0.0009 – 0.0150 0.027
time_since_entry:birth_cohort_cat_updated1930 0.0088 -0.0001 – 0.0177 0.052 0.0089 0.0001 – 0.0177 0.049
time_since_entry:birth_cohort_cat_updated1935-1950 0.0310 0.0231 – 0.0390 <0.001 0.0308 0.0228 – 0.0387 <0.001
time_since_entry:apoe+ APOE e4 -0.0255 -0.0313 – -0.0197 <0.001 -0.0254 -0.0312 – -0.0196 <0.001
Random Effects
σ2 0.23 0.23
τ00 0.27 SUBJECT 0.27 SUBJECT
τ11 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry
ρ01 0.09 SUBJECT 0.09 SUBJECT
ICC 0.66 0.65
N 4287 SUBJECT 4289 SUBJECT
Observations 22935 22947
Marginal R2 / Conditional R2 0.236 / 0.737 0.236 / 0.735

Model with calender year added


  Model 2, PM 2.5 Model 2, NO2
Predictors Estimates CI p Estimates CI p
(Intercept) 0.2080 -0.1632 – 0.5792 0.272 0.4999 0.3836 – 0.6162 <0.001
Baseline PM2.5 (5 year) 0.0024 -0.0247 – 0.0296 0.861
time_since_entry:exp_avg_pm25_05_yr 0.0125 0.0102 – 0.0148 <0.001
Baseline NO2 (5 year) -0.0187 -0.0246 – -0.0128 <0.001
time_since_entry:exp_avg_no2_05_yr 0.0021 0.0015 – 0.0027 <0.001
Baseline Age (centered) -0.0528 -0.0608 – -0.0448 <0.001 -0.0577 -0.0656 – -0.0498 <0.001
Gender: Male -0.1832 -0.2194 – -0.1471 <0.001 -0.1829 -0.2192 – -0.1466 <0.001
Time Since Entry -0.1778 -0.1958 – -0.1597 <0.001 -0.1135 -0.1259 – -0.1011 <0.001
birth_cohort_cat_updated1890-1905 0.2172 0.0557 – 0.3787 0.008 0.3032 0.1429 – 0.4635 <0.001
Birth Cohort: 1910 0.1130 0.0031 – 0.2229 0.044 0.1644 0.0551 – 0.2737 0.003
Birth Cohort: 1915 0.0744 0.0010 – 0.1479 0.047 0.0992 0.0257 – 0.1727 0.008
Birth Cohort: 1925 -0.1306 -0.1995 – -0.0617 <0.001 -0.1546 -0.2235 – -0.0857 <0.001
Birth Cohort: 1930 -0.2189 -0.3284 – -0.1095 <0.001 -0.3046 -0.4122 – -0.1969 <0.001
birth_cohort_cat_updated1935-1950 -0.3327 -0.4896 – -0.1757 <0.001 -0.4083 -0.5652 – -0.2514 <0.001
APOE Status: + APOE e4 -0.0570 -0.0986 – -0.0154 0.007 -0.0606 -0.1025 – -0.0187 0.005
cal_year: cal_year1995 0.0417 -0.0176 – 0.1010 0.168 0.0588 0.0022 – 0.1154 0.042
cal_year: cal_year1996 0.0957 0.0347 – 0.1567 0.002 0.1849 0.1349 – 0.2348 <0.001
cal_year: cal_year1997 0.1919 0.1118 – 0.2721 <0.001 0.3038 0.2429 – 0.3646 <0.001
cal_year: cal_year1998 0.2986 0.2126 – 0.3847 <0.001 0.4275 0.3679 – 0.4871 <0.001
cal_year: cal_year1999 0.3822 0.2783 – 0.4861 <0.001 0.5133 0.4423 – 0.5842 <0.001
cal_year: cal_year2000 0.3378 0.2257 – 0.4499 <0.001 0.4739 0.4008 – 0.5471 <0.001
cal_year: cal_year2001 0.3726 0.2442 – 0.5009 <0.001 0.5098 0.4279 – 0.5918 <0.001
cal_year: cal_year2002 0.3314 0.1952 – 0.4675 <0.001 0.4558 0.3701 – 0.5415 <0.001
cal_year: cal_year2003 0.3455 0.1943 – 0.4967 <0.001 0.4822 0.3883 – 0.5761 <0.001
cal_year: cal_year2004 0.3589 0.1955 – 0.5223 <0.001 0.4986 0.3979 – 0.5993 <0.001
cal_year: cal_year2005 0.4794 0.3044 – 0.6543 <0.001 0.6095 0.5010 – 0.7180 <0.001
cal_year: cal_year2006 0.4719 0.2872 – 0.6565 <0.001 0.5940 0.4796 – 0.7084 <0.001
cal_year: cal_year2007 0.4947 0.2983 – 0.6912 <0.001 0.6105 0.4881 – 0.7329 <0.001
cal_year: cal_year2008 0.4871 0.2826 – 0.6915 <0.001 0.5830 0.4552 – 0.7107 <0.001
cal_year: cal_year2009 0.5203 0.3059 – 0.7347 <0.001 0.5933 0.4582 – 0.7285 <0.001
cal_year: cal_year2010 0.5553 0.3339 – 0.7767 <0.001 0.6108 0.4711 – 0.7505 <0.001
cal_year: cal_year2011 0.5683 0.3399 – 0.7966 <0.001 0.5778 0.4315 – 0.7241 <0.001
cal_year: cal_year2012 0.5837 0.3466 – 0.8208 <0.001 0.5829 0.4307 – 0.7350 <0.001
cal_year: cal_year2013 0.6204 0.3754 – 0.8655 <0.001 0.5932 0.4348 – 0.7516 <0.001
cal_year: cal_year2014 0.6332 0.3793 – 0.8871 <0.001 0.5884 0.4239 – 0.7528 <0.001
cal_year: cal_year2015 0.5842 0.3202 – 0.8482 <0.001 0.5354 0.3637 – 0.7072 <0.001
cal_year: cal_year2016 0.6089 0.3354 – 0.8825 <0.001 0.5425 0.3642 – 0.7209 <0.001
cal_year: cal_year2017 0.6107 0.3299 – 0.8914 <0.001 0.5215 0.3369 – 0.7061 <0.001
cal_year: cal_year2018 0.5634 0.2723 – 0.8545 <0.001 0.4608 0.2686 – 0.6529 <0.001
cal_year: cal_year2019 0.4207 0.1199 – 0.7215 0.006 0.3177 0.1181 – 0.5173 0.002
cal_year: cal_year2020 0.4066 0.0845 – 0.7287 0.013 0.2965 0.0705 – 0.5225 0.010
age85:time_since_entry -0.0003 -0.0031 – 0.0025 0.858 -0.0034 -0.0061 – -0.0007 0.015
time_since_entry:birth_cohort_cat_updated1890-1905 -0.0791 -0.0994 – -0.0588 <0.001 -0.0746 -0.0947 – -0.0544 <0.001
time_since_entry:birth_cohort_cat_updated1910 -0.0469 -0.0604 – -0.0334 <0.001 -0.0430 -0.0564 – -0.0297 <0.001
time_since_entry:birth_cohort_cat_updated1915 -0.0266 -0.0360 – -0.0172 <0.001 -0.0247 -0.0340 – -0.0154 <0.001
time_since_entry:birth_cohort_cat_updated1925 0.0232 0.0153 – 0.0311 <0.001 0.0222 0.0145 – 0.0300 <0.001
time_since_entry:birth_cohort_cat_updated1930 0.0489 0.0382 – 0.0596 <0.001 0.0540 0.0436 – 0.0644 <0.001
time_since_entry:birth_cohort_cat_updated1935-1950 0.0983 0.0873 – 0.1094 <0.001 0.1024 0.0917 – 0.1131 <0.001
time_since_entry:apoe+ APOE e4 -0.0290 -0.0353 – -0.0227 <0.001 -0.0289 -0.0351 – -0.0227 <0.001
Random Effects
σ2 0.22 0.22
τ00 0.26 SUBJECT 0.26 SUBJECT
τ11 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry
ρ01 0.10 SUBJECT 0.10 SUBJECT
ICC 0.70 0.70
N 4287 SUBJECT 4289 SUBJECT
Observations 22935 22947
Marginal R2 / Conditional R2 0.270 / 0.782 0.267 / 0.778

Analysis with baseline exposure only


Model 1

  PM 2.5 PM2.5, Baseline Only NO2 NO2, Baseline Only
Predictors Estimates CI p Estimates CI p Estimates CI p Estimates CI p
(Intercept) 0.7199 0.6550 – 0.7848 <0.001 0.5558 0.4888 – 0.6227 <0.001 0.6400 0.5609 – 0.7191 <0.001 0.5438 0.4621 – 0.6255 <0.001
Baseline PM2.5 (5 year) -0.0374 -0.0435 – -0.0312 <0.001 -0.0184 -0.0246 – -0.0122 <0.001
time_since_entry:exp_avg_pm25_05_yr 0.0099 0.0088 – 0.0111 <0.001
baseline_pm25_05_yr:time_since_entry -0.0018 -0.0027 – -0.0009 <0.001
Baseline NO2 (5 year) -0.0186 -0.0237 – -0.0135 <0.001 -0.0117 -0.0169 – -0.0064 <0.001
time_since_entry:exp_avg_no2_05_yr 0.0022 0.0017 – 0.0026 <0.001
baseline_no2_05_yr:time_since_entry -0.0011 -0.0019 – -0.0004 0.003
Baseline Age (centered) -0.0443 -0.0471 – -0.0415 <0.001 -0.0442 -0.0470 – -0.0414 <0.001 -0.0448 -0.0476 – -0.0420 <0.001 -0.0447 -0.0474 – -0.0419 <0.001
Time Since Entry -0.1133 -0.1221 – -0.1044 <0.001 -0.0214 -0.0319 – -0.0110 <0.001 -0.0700 -0.0766 – -0.0633 <0.001 -0.0235 -0.0354 – -0.0115 <0.001
age85:time_since_entry -0.0167 -0.0191 – -0.0143 <0.001 -0.0246 -0.0267 – -0.0225 <0.001 -0.0216 -0.0238 – -0.0193 <0.001 -0.0249 -0.0270 – -0.0228 <0.001
Random Effects
σ2 0.23 0.23 0.23 0.23
τ00 0.28 SUBJECT 0.28 SUBJECT 0.28 SUBJECT 0.28 SUBJECT
τ11 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry
ρ01 -0.01 SUBJECT 0.03 SUBJECT 0.01 SUBJECT 0.03 SUBJECT
ICC 0.68 0.66 0.67 0.66
N 4903 SUBJECT 4903 SUBJECT 4906 SUBJECT 4906 SUBJECT
Observations 25541 25639 25555 25658
Marginal R2 / Conditional R2 0.202 / 0.746 0.210 / 0.730 0.193 / 0.732 0.198 / 0.726



Model 2

  PM 2.5 PM2.5, Baseline Only NO2 NO2, Baseline Only
Predictors Estimates CI p Estimates CI p Estimates CI p Estimates CI p
(Intercept) 0.9507 0.7494 – 1.1520 <0.001 0.8810 0.6743 – 1.0877 <0.001 0.7414 0.6395 – 0.8433 <0.001 0.6410 0.5364 – 0.7456 <0.001
Baseline PM2.5 (5 year) -0.0467 -0.0633 – -0.0301 <0.001 -0.0335 -0.0505 – -0.0166 <0.001
time_since_entry:exp_avg_pm25_05_yr 0.0172 0.0159 – 0.0186 <0.001
baseline_pm25_05_yr:time_since_entry 0.0036 0.0021 – 0.0052 <0.001
Baseline NO2 (5 year) -0.0177 -0.0235 – -0.0119 <0.001 -0.0103 -0.0162 – -0.0044 0.001
time_since_entry:exp_avg_no2_05_yr 0.0039 0.0034 – 0.0045 <0.001
baseline_no2_05_yr:time_since_entry -0.0001 -0.0009 – 0.0007 0.788
Baseline Age (centered) -0.0454 -0.0526 – -0.0382 <0.001 -0.0465 -0.0538 – -0.0392 <0.001 -0.0371 -0.0417 – -0.0325 <0.001 -0.0381 -0.0428 – -0.0335 <0.001
Gender: Male -0.1856 -0.2216 – -0.1496 <0.001 -0.1852 -0.2216 – -0.1488 <0.001 -0.1837 -0.2199 – -0.1475 <0.001 -0.1843 -0.2207 – -0.1480 <0.001
Time Since Entry -0.1791 -0.1914 – -0.1669 <0.001 -0.0877 -0.1079 – -0.0675 <0.001 -0.1013 -0.1108 – -0.0918 <0.001 -0.0409 -0.0547 – -0.0270 <0.001
birth_cohort_cat_updated1890-1905 0.0938 -0.0593 – 0.2469 0.230 0.0623 -0.0930 – 0.2175 0.432 -0.0712 -0.1963 – 0.0538 0.264 -0.0718 -0.1976 – 0.0539 0.263
Birth Cohort: 1910 0.0369 -0.0684 – 0.1421 0.492 0.0086 -0.0981 – 0.1153 0.874 -0.0735 -0.1625 – 0.0155 0.105 -0.0783 -0.1677 – 0.0111 0.086
Birth Cohort: 1915 0.0354 -0.0361 – 0.1068 0.332 0.0088 -0.0637 – 0.0814 0.811 -0.0211 -0.0875 – 0.0453 0.533 -0.0314 -0.0980 – 0.0353 0.356
Birth Cohort: 1925 -0.0841 -0.1506 – -0.0175 0.013 -0.0614 -0.1289 – 0.0061 0.075 -0.0232 -0.0838 – 0.0374 0.453 -0.0137 -0.0745 – 0.0472 0.660
Birth Cohort: 1930 -0.0917 -0.1915 – 0.0081 0.072 -0.0938 -0.1956 – 0.0080 0.071 0.0358 -0.0353 – 0.1068 0.324 0.0411 -0.0303 – 0.1124 0.259
birth_cohort_cat_updated1935-1950 -0.1258 -0.2552 – 0.0036 0.057 -0.1311 -0.2630 – 0.0009 0.052 0.0443 -0.0187 – 0.1074 0.168 0.0560 -0.0074 – 0.1195 0.084
APOE Status: + APOE e4 -0.0583 -0.1000 – -0.0167 0.006 -0.0672 -0.1095 – -0.0249 0.002 -0.0629 -0.1049 – -0.0208 0.003 -0.0677 -0.1100 – -0.0254 0.002
age85:time_since_entry -0.0023 -0.0051 – 0.0005 0.101 -0.0211 -0.0234 – -0.0188 <0.001 -0.0131 -0.0157 – -0.0106 <0.001 -0.0215 -0.0238 – -0.0192 <0.001
time_since_entry:birth_cohort_cat_updated1890-1905 -0.0712 -0.0914 – -0.0511 <0.001 -0.0379 -0.0571 – -0.0187 <0.001 -0.0477 -0.0674 – -0.0280 <0.001 -0.0355 -0.0547 – -0.0163 <0.001
time_since_entry:birth_cohort_cat_updated1910 -0.0416 -0.0550 – -0.0283 <0.001 -0.0142 -0.0266 – -0.0018 0.024 -0.0240 -0.0369 – -0.0111 <0.001 -0.0122 -0.0245 – 0.0002 0.054
time_since_entry:birth_cohort_cat_updated1915 -0.0244 -0.0337 – -0.0152 <0.001 -0.0090 -0.0175 – -0.0005 0.039 -0.0157 -0.0247 – -0.0068 0.001 -0.0082 -0.0168 – 0.0003 0.059
time_since_entry:birth_cohort_cat_updated1925 0.0206 0.0129 – 0.0284 <0.001 0.0094 0.0024 – 0.0164 0.009 0.0137 0.0062 – 0.0211 <0.001 0.0075 0.0005 – 0.0145 0.035
time_since_entry:birth_cohort_cat_updated1930 0.0346 0.0250 – 0.0443 <0.001 0.0220 0.0115 – 0.0326 <0.001 0.0209 0.0116 – 0.0302 <0.001 0.0084 -0.0004 – 0.0171 0.062
time_since_entry:birth_cohort_cat_updated1935-1950 0.0688 0.0599 – 0.0777 <0.001 0.0490 0.0378 – 0.0602 <0.001 0.0502 0.0417 – 0.0588 <0.001 0.0305 0.0224 – 0.0385 <0.001
time_since_entry:apoe+ APOE e4 -0.0279 -0.0341 – -0.0218 <0.001 -0.0251 -0.0309 – -0.0194 <0.001 -0.0266 -0.0326 – -0.0206 <0.001 -0.0249 -0.0307 – -0.0192 <0.001
Random Effects
σ2 0.22 0.23 0.23 0.23
τ00 0.26 SUBJECT 0.27 SUBJECT 0.26 SUBJECT 0.27 SUBJECT
τ11 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry
ρ01 0.10 SUBJECT 0.10 SUBJECT 0.07 SUBJECT 0.09 SUBJECT
ICC 0.69 0.65 0.67 0.65
N 4287 SUBJECT 4287 SUBJECT 4289 SUBJECT 4289 SUBJECT
Observations 22935 23023 22947 23040
Marginal R2 / Conditional R2 0.263 / 0.770 0.235 / 0.735 0.247 / 0.751 0.235 / 0.735



Model 2, No Birth Cohort in Longitudinal Portion

  PM 2.5 PM2.5, No BC in Longitudinal NO2 NO2, No BC in Longitudinal
Predictors Estimates CI p Estimates CI p Estimates CI p Estimates CI p
(Intercept) 0.8810 0.6743 – 1.0877 <0.001 0.7298 0.5262 – 0.9335 <0.001 0.6410 0.5364 – 0.7456 <0.001 0.5879 0.4839 – 0.6919 <0.001
Baseline PM2.5 (5 year) -0.0335 -0.0505 – -0.0166 <0.001 -0.0223 -0.0391 – -0.0055 0.009
baseline_pm25_05_yr:time_since_entry 0.0036 0.0021 – 0.0052 <0.001 -0.0021 -0.0031 – -0.0011 <0.001
Baseline NO2 (5 year) -0.0103 -0.0162 – -0.0044 0.001 -0.0080 -0.0139 – -0.0021 0.008
baseline_no2_05_yr:time_since_entry -0.0001 -0.0009 – 0.0007 0.788 -0.0011 -0.0018 – -0.0003 0.008
Baseline Age (centered) -0.0465 -0.0538 – -0.0392 <0.001 -0.0462 -0.0534 – -0.0389 <0.001 -0.0381 -0.0428 – -0.0335 <0.001 -0.0378 -0.0425 – -0.0332 <0.001
Gender: Male -0.1852 -0.2216 – -0.1488 <0.001 -0.1835 -0.2198 – -0.1471 <0.001 -0.1843 -0.2207 – -0.1480 <0.001 -0.1822 -0.2184 – -0.1459 <0.001
Time Since Entry -0.0877 -0.1079 – -0.0675 <0.001 -0.0123 -0.0233 – -0.0013 0.028 -0.0409 -0.0547 – -0.0270 <0.001 -0.0185 -0.0311 – -0.0060 0.004
birth_cohort_cat_updated1890-1905 0.0623 -0.0930 – 0.2175 0.432 -0.0080 -0.1584 – 0.1423 0.917 -0.0718 -0.1976 – 0.0539 0.263 -0.1376 -0.2574 – -0.0177 0.025
Birth Cohort: 1910 0.0086 -0.0981 – 0.1153 0.874 -0.0164 -0.1200 – 0.0872 0.756 -0.0783 -0.1677 – 0.0111 0.086 -0.0997 -0.1855 – -0.0139 0.023
Birth Cohort: 1915 0.0088 -0.0637 – 0.0814 0.811 -0.0078 -0.0782 – 0.0626 0.828 -0.0314 -0.0980 – 0.0353 0.356 -0.0478 -0.1121 – 0.0166 0.146
Birth Cohort: 1925 -0.0614 -0.1289 – 0.0061 0.075 -0.0436 -0.1097 – 0.0225 0.196 -0.0137 -0.0745 – 0.0472 0.660 0.0016 -0.0577 – 0.0609 0.959
Birth Cohort: 1930 -0.0938 -0.1956 – 0.0080 0.071 -0.0500 -0.1494 – 0.0493 0.324 0.0411 -0.0303 – 0.1124 0.259 0.0591 -0.0099 – 0.1281 0.093
birth_cohort_cat_updated1935-1950 -0.1311 -0.2630 – 0.0009 0.052 -0.0277 -0.1573 – 0.1020 0.676 0.0560 -0.0074 – 0.1195 0.084 0.1244 0.0633 – 0.1854 <0.001
APOE Status: + APOE e4 -0.0672 -0.1095 – -0.0249 0.002 -0.0700 -0.1124 – -0.0277 0.001 -0.0677 -0.1100 – -0.0254 0.002 -0.0710 -0.1133 – -0.0286 0.001
age85:time_since_entry -0.0211 -0.0234 – -0.0188 <0.001 -0.0239 -0.0261 – -0.0216 <0.001 -0.0215 -0.0238 – -0.0192 <0.001 -0.0244 -0.0266 – -0.0222 <0.001
time_since_entry:birth_cohort_cat_updated1890-1905 -0.0379 -0.0571 – -0.0187 <0.001 -0.0355 -0.0547 – -0.0163 <0.001
time_since_entry:birth_cohort_cat_updated1910 -0.0142 -0.0266 – -0.0018 0.024 -0.0122 -0.0245 – 0.0002 0.054
time_since_entry:birth_cohort_cat_updated1915 -0.0090 -0.0175 – -0.0005 0.039 -0.0082 -0.0168 – 0.0003 0.059
time_since_entry:birth_cohort_cat_updated1925 0.0094 0.0024 – 0.0164 0.009 0.0075 0.0005 – 0.0145 0.035
time_since_entry:birth_cohort_cat_updated1930 0.0220 0.0115 – 0.0326 <0.001 0.0084 -0.0004 – 0.0171 0.062
time_since_entry:birth_cohort_cat_updated1935-1950 0.0490 0.0378 – 0.0602 <0.001 0.0305 0.0224 – 0.0385 <0.001
time_since_entry:apoe+ APOE e4 -0.0251 -0.0309 – -0.0194 <0.001 -0.0236 -0.0294 – -0.0178 <0.001 -0.0249 -0.0307 – -0.0192 <0.001 -0.0233 -0.0291 – -0.0175 <0.001
Random Effects
σ2 0.23 0.23 0.23 0.23
τ00 0.27 SUBJECT 0.27 SUBJECT 0.27 SUBJECT 0.27 SUBJECT
τ11 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry 0.00 SUBJECT.time_since_entry
ρ01 0.10 SUBJECT 0.06 SUBJECT 0.09 SUBJECT 0.06 SUBJECT
ICC 0.65 0.65 0.65 0.65
N 4287 SUBJECT 4287 SUBJECT 4289 SUBJECT 4289 SUBJECT
Observations 23023 23023 23040 23040
Marginal R2 / Conditional R2 0.235 / 0.735 0.223 / 0.730 0.235 / 0.735 0.216 / 0.726