Non-Cancer Chronic Pain Conditions and Risk for Incident Alzheimer’s Disease and Related Dementias in Community-Dwelling Older Adults: A Population-Based Retrospective Cohort Study of United States Medicare Beneficiaries, 2001–2013
Abstract
:1. Introduction
2. Methods
2.1. Study Design
2.2. Data Source
2.3. Study Sample
2.4. Dependent Variable: Incident Alzheimer’s Disease and Related Dementia (ADRD) at Follow-Up– Yes/No
2.5. Key Independent Variable: Non-Cancer Chronic Pain Condition (NCPC) and Number of NCPCs
2.6. Covariates
2.7. Statistical Analysis
3. Results
3.1. Association of NCPC to Incident ADRD
3.2. Sensitivity Analyses
3.3. Potential Mediating Effects of Sleep and Mood Disorders
4. Discussion
Strengths and Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variables | Total | Any NCPC | p-Value § | ||||
---|---|---|---|---|---|---|---|
Yes | No | ||||||
N ¥ | Wt.% | N | Wt.% | N | Wt. % | ||
ALL¥ | 16,934 | 100 | 6369 | 100.0 | 10,565 | 100.0 | |
Sociodemographics | |||||||
Sex | <0.0001 | ||||||
Female | 9669 | 56.9 | 4215 | 66.4 | 5454 | 51.5 | |
Male | 7265 | 43.1 | 2154 | 33.6 | 5111 | 48.5 | |
Age in Years | <0.0001 | ||||||
65–69 | 4188 | 31.8 | 1335 | 26.4 | 2853 | 34.9 | |
70–74 | 3484 | 22.5 | 1230 | 22.1 | 2254 | 22.8 | |
75–79 | 3674 | 21.4 | 1411 | 22.8 | 2263 | 20.6 | |
80+ | 5588 | 24.3 | 2393 | 28.8 | 3195 | 21.7 | |
Race/Ethnicity | 0.842 | ||||||
White | 14,085 | 83.2 | 5293 | 83.4 | 8792 | 83.0 | |
Black | 1159 | 6.7 | 438 | 6.7 | 721 | 6.7 | |
Hispanic | 956 | 5.6 | 359 | 5.7 | 597 | 5.6 | |
Other | 709 | 4.5 | 268 | 4.3 | 441 | 4.6 | |
Education | <0.0001 | ||||||
<High School | 4605 | 25.0 | 1744 | 25.4 | 2861 | 24.7 | |
High School | 6174 | 36.4 | 2349 | 37.0 | 3825 | 36.1 | |
Some College | 2431 | 15.0 | 950 | 15.7 | 1481 | 14.6 | |
College | 3675 | 23.6 | 1306 | 21.9 | 2369 | 24.6 | |
Marital Status | <0.0001 | ||||||
Married | 9139 | 56.5 | 3208 | 52.8 | 5931 | 58.7 | |
Widowed | 5803 | 30.6 | 2491 | 35.7 | 3312 | 27.6 | |
Divorce/separated | 1455 | 9.5 | 490 | 8.3 | 965 | 10.2 | |
Other | 532 | 3.3 | 179 | 3.1 | 353 | 3.5 | |
Household Income | <0.0001 | ||||||
<200% Federal Poverty Level | 8260 | 45.9 | 3221 | 48.4 | 5039 | 44.6 | |
≥200% Federal Poverty Level | 8674 | 54.1 | 3148 | 51.6 | 5526 | 55.4 | |
Insurance | |||||||
Medicaid | <0.0001 | ||||||
Yes | 2147 | 11.9 | 1005 | 15.4 | 1142 | 9.9 | |
No | 14,787 | 88.1 | 5364 | 84.6 | 9423 | 90.1 | |
Private Insurance | 0.001 | ||||||
Yes | 13,418 | 79.4 | 5147 | 80.8 | 8271 | 78.5 | |
No | 3514 | 20.6 | 1221 | 19.2 | 2293 | 21.5 | |
Residence | |||||||
Metropolitan Status | <0.0001 | ||||||
Metro | 11,375 | 70.6 | 4415 | 72.5 | 6960 | 69.5 | |
Rural | 5558 | 29.4 | 1954 | 27.5 | 3604 | 30.5 | |
Lifestyle Characteristics | |||||||
Body Mass Index | <0.0001 | ||||||
Underweight | 312 | 1.7 | 100 | 1.4 | 212 | 1.8 | |
Normal | 5867 | 34.0 | 1984 | 30.4 | 3883 | 36.0 | |
Overweight | 6709 | 40.0 | 2491 | 39.2 | 4218 | 40.5 | |
Obese | 3881 | 24.3 | 1734 | 29.0 | 2147 | 21.7 | |
Mean BMI 27.2 (±0.052) | |||||||
Smoking Status | <0.0001 | ||||||
Current | 1594 | 10.2 | 457 | 7.8 | 1137 | 11.5 | |
Past | 7976 | 47.5 | 2965 | 47.2 | 5011 | 47.6 | |
Never | 7326 | 42.4 | 2936 | 45.1 | 4390 | 40.8 | |
Baseline Health History | |||||||
Physical Health Conditions | |||||||
Hypertension | <0.0001 | ||||||
Yes | 12,713 | 73.5 | 5263 | 82.0 | 7450 | 68.7 | |
No | 4221 | 26.5 | 1106 | 18.0 | 3115 | 31.3 | |
Heart disease | <0.0001 | ||||||
Yes | 4357 | 24.1 | 2097 | 31.5 | 2260 | 19.9 | |
No | 12,577 | 75.9 | 4272 | 68.5 | 8305 | 80.1 | |
Stroke | <0.0001 | ||||||
Yes | 2139 | 11.5 | 979 | 14.3 | 1160 | 9.9 | |
No | 14,795 | 88.5 | 5390 | 85.7 | 9405 | 90.1 | |
Diabetes | <0.0001 | ||||||
Yes | 3495 | 20.7 | 1468 | 23.5 | 2027 | 19.2 | |
No | 13,439 | 79.3 | 4901 | 76.5 | 8538 | 80.8 | |
Respiratory disease | <0.0001 | ||||||
Yes | 2423 | 14.2 | 1045 | 16.7 | 1378 | 12.7 | |
No | 14,511 | 85.8 | 5324 | 83.3 | 9187 | 87.3 | |
Cancer | <0.0001 | ||||||
Yes | 7101 | 40.3 | 2911 | 44.4 | 4190 | 38.0 | |
No | 9833 | 59.7 | 3458 | 55.6 | 6375 | 62.0 | |
Traumatic Brain Injury | <0.0001 | ||||||
Yes | 221 | 1.2 | 146 | 2.2 | 75 | 0.7 | |
No | 16,713 | 98.8 | 6223 | 97.8 | 10,490 | 99.3 | |
Rheumatoid Arthritis | <0.0001 | ||||||
Yes | 508 | 2.9 | 349 | 5.5 | 159 | 1.4 | |
No | 16,426 | 97.1 | 6020 | 94.5 | 10,406 | 98.6 | |
Lupus | <0.0001 | ||||||
Yes | 136 | 0.8 | 94 | 1.4 | 42 | 0.4 | |
No | 16,798 | 99.2 | 6275 | 98.6 | 10,523 | 99.6 | |
Number of NCPCs | |||||||
0 | 6385 | 39.1 | - | - | - | - | - |
1 | 4194 | 24.4 | - | - | - | - | - |
2 | 3818 | 22.0 | - | - | - | - | - |
3 | 1908 | 10.9 | - | - | - | - | - |
≥4 | 629 | 3.7 | - | - | - | - | - |
Sleep and Mood Disorders | |||||||
Sleep Disorder | <0.0001 | ||||||
Yes | 2728 | 15.8 | 1630 | 25.5 | 1098 | 10.2 | |
No | 14,206 | 84.2 | 4739 | 74.5 | 9467 | 89.8 | |
Depression | <0.0001 | ||||||
Yes | 1158 | 6.9 | 686 | 11.1 | 472 | 4.5 | |
No | 15,776 | 93.1 | 5683 | 88.9 | 10,093 | 95.5 | |
Anxiety | <0.0001 | ||||||
Yes | 862 | 5.1 | 492 | 7.9 | 370 | 3.5 | |
No | 16,072 | 94.9 | 5877 | 92.1 | 10,195 | 96.5 | |
Medication Use | |||||||
NSAIDs | <0.0001 | ||||||
Yes | 3241 | 18.6 | 1936 | 30.2 | 1305 | 12.0 | |
No | 13,693 | 81.4 | 4433 | 69.8 | 9260 | 88.0 | |
Opioid Analgesics | <0.0001 | ||||||
Yes | 3353 | 19.4 | 2059 | 32.2 | 1294 | 12.0 | |
No | 13,581 | 80.6 | 4310 | 67.8 | 9271 | 88.0 | |
Benzodiazepines | <0.0001 | ||||||
Yes | 1734 | 9.7 | 935 | 14.5 | 799 | 7.1 | |
No | 15,200 | 90.3 | 5434 | 85.5 | 9766 | 92.9 | |
Psychotropic medications | <0.0001 | ||||||
Yes | 2871 | 17.0 | 1448 | 23.3 | 1423 | 13.5 | |
No | 14,063 | 83.0 | 4921 | 76.7 | 9142 | 86.5 |
Variables | Incident ADRD | p-Value § | |||
---|---|---|---|---|---|
Yes | No | ||||
N | Wt. % | N | Wt. % | ||
ALL¥ | 1149 | 6.8 | 15,785 | 93.2 | |
Any NCPC | <0.0001 | ||||
Yes | 798 | 6.6 | 9677 | 93.4 | |
No | 351 | 4.3 | 6108 | 95.7 | |
Number of NCPC’s | <0.0001 | ||||
0 | 351 | 4.3 | 6108 | 95.7 | |
1 | 304 | 6.2 | 3948 | 93.8 | |
2 | 273 | 6.0 | 3605 | 94.0 | |
3 | 155 | 7.3 | 1742 | 92.7 | |
≥4 | 66 | 17.3 | 382 | 82.7 | |
Sociodemographic | |||||
Sex | <0.0001 | ||||
Female | 725 | 6.2 | 8944 | 93.8 | |
Male | 424 | 5 | 6841 | 95 | |
Age in Years | <0.0001 | ||||
65–69 | 101 | 1.9 | 4087 | 98.1 | |
70–74 | 139 | 4 | 3345 | 96 | |
75–79 | 220 | 5.9 | 3454 | 94.1 | |
80+ | 689 | 12 | 4899 | 88 | |
Race/Ethnicity | 0.066 | ||||
White | 922 | 5.5 | 13,163 | 94.5 | |
Black | 106 | 7.4 | 1053 | 92.6 | |
Hispanic | 70 | 5.9 | 886 | 94.1 | |
Other | 51 | 6.5 | 658 | 93.5 | |
Education | <0.0001 | ||||
<High School | 417 | 7.8 | 4188 | 92.2 | |
High School | 398 | 5.5 | 5776 | 94.5 | |
Some College | 141 | 4.8 | 2290 | 95.2 | |
College | 186 | 4.1 | 3489 | 95.9 | |
Marital Status | <0.0001 | ||||
Married | 494 | 4.5 | 8645 | 95.5 | |
Widowed | 541 | 8.2 | 5262 | 91.8 | |
Divorce/separated | 76 | 4.4 | 1379 | 95.6 | |
Other | 38 | 6 | 494 | 94 | |
Household Income | <0.0001 | ||||
<200% Federal Poverty Level | 699 | 7.4 | 7561 | 92.6 | |
≥200% Federal Poverty Level | 450 | 4.3 | 8224 | 95.7 | |
Insurance | |||||
Medicaid | <0.0001 | ||||
Yes | 223 | 9.1 | 1924 | 90.9 | |
No | 926 | 5.2 | 13,861 | 94.8 | |
Private Insurance | <0.0001 | ||||
Yes | 847 | 5.3 | 12,571 | 94.7 | |
No | 300 | 7.2 | 3214 | 92.8 | |
Residence | 0.649 | ||||
Metropolitan Status | |||||
Metro | 787 | 5.7 | 10,588 | 94.3 | |
Rural | 362 | 5.5 | 5196 | 94.5 | |
Lifestyle Characteristics | |||||
Body Mass Index | <0.0001 | ||||
Underweight | 43 | 12.2 | 269 | 87.8 | |
Normal | 484 | 6.9 | 5383 | 93.1 | |
Overweight | 417 | 5.2 | 6292 | 94.8 | |
Obese | 195 | 4.3 | 3686 | 95.7 | |
Smoking Status | <0.0001 | ||||
Current | 96 | 4.8 | 1498 | 95.2 | |
Past | 472 | 5 | 7504 | 95 | |
Never | 580 | 6.6 | 6746 | 93.4 | |
Baseline Health History | |||||
Physical Health Conditions | |||||
Hypertension | <0.0001 | ||||
Yes | 935 | 6.3 | 11,778 | 93.7 | |
No | 214 | 4.1 | 4007 | 95.9 | |
Heart disease | <0.0001 | ||||
Yes | 368 | 7.6 | 3989 | 92.4 | |
No | 781 | 5.1 | 11,796 | 94.9 | |
Stroke | <0.0001 | ||||
Yes | 281 | 11.9 | 1858 | 88.1 | |
No | 868 | 4.9 | 13,927 | 95.1 | |
Diabetes | 0.032 | ||||
Yes | 264 | 6.4 | 3231 | 93.6 | |
No | 885 | 5.5 | 12,554 | 94.5 | |
Respiratory disease | 0.576 | ||||
Yes | 170 | 5.9 | 2253 | 94.1 | |
No | 979 | 5.6 | 13,532 | 94.4 | |
Cancer | 0.043 | ||||
Yes | 505 | 6.2 | 6596 | 93.8 | |
No | 644 | 5.3 | 9189 | 94.7 | |
Traumatic Brain Injury | <0.0001 | ||||
Yes | 30 | 12.8 | 191 | 87.2 | |
No | 1119 | 5.6 | 15,594 | 94.4 | |
Rheumatoid Arthritis | 0.247 | ||||
Yes | 39 | 6.8 | 469 | 93.2 | |
No | 1110 | 5.6 | 15,316 | 94.4 | |
Lupus | 0.119 | ||||
Yes | 13 | 8.9 | 123 | 91.1 | |
No | 1136 | 5.7 | 15,662 | 94.3 | |
Sleep and Mood Disorders | |||||
Sleep Disorder | <0.0001 | ||||
Yes | 267 | 8.5 | 2461 | 91.5 | |
No | 882 | 5.2 | 13,324 | 94.8 | |
Depression | <0.0001 | ||||
Yes | 170 | 12.9 | 988 | 87.1 | |
No | 979 | 5.1 | 14,797 | 94.9 | |
Anxiety | <0.0001 | ||||
Yes | 109 | 10.9 | 753 | 89.1 | |
No | 1040 | 5.4 | 15,032 | 94.6 | |
Medication Use | |||||
NSAIDs | 0.496 | ||||
Yes | 226 | 6 | 3015 | 94 | |
No | 923 | 5.6 | 12,770 | 94.4 | |
Opioid Analgesics | <0.0001 | ||||
Yes | 266 | 6.9 | 3087 | 93.1 | |
No | 883 | 5.4 | 12,698 | 94.6 | |
Benzodiazepines | <0.0001 | ||||
Yes | 167 | 8.5 | 1567 | 91.5 | |
No | 982 | 5.4 | 14,218 | 94.6 |
NCPC Presence/Number | Unadjusted Model | Model 1 ¥ | Model 2 ¥¥ | Model 3 ⱡⱡ | ||||
---|---|---|---|---|---|---|---|---|
OR (95% CI) | p | AOR (95% CI) | p | AOR (95% CI) | p | AOR (95% CI) | p | |
Any NCPC ** vs. None | 1.54 (1.34,1.78) | <0.0001 | 1.33 (1.14,1.53) | <0.0001 | 1.28 (1.10,1.48) | 0.001 | 1.25 (1.08,1.45) | 0.003 |
Number of NCPCs | ||||||||
None (referent) | 1.00 | 1.00 | 1.00 | 1.00 | ||||
One | 1.47 (1.26,1.71) | <0.0001 | 1.27 (1.08,1.50) | 0.0039 | 1.24 (1.05,1.46) | 0.0125 | 1.23 (1.04,1.45) | 0.0179 |
Two | 1.42 (1.20,1.68) | <0.0001 | 1.25 (1.05,1.49) | 0.0121 | 1.22 (1.02,1.45) | 0.0278 | 1.20 (1.01,1.43) | 0.0435 |
Three | 1.75 (1.42,2.16) | <0.0001 | 1.45 (1.17,1.80) | 0.0007 | 1.38 (1.11,1.71) | 0.0041 | 1.34 (1.07,1.68) | 0.0122 |
Four or more | 3.03 (2.14,4.29) | <0.0001 | 2.32 (1.62,3.31) | <0.0001 | 1.98 (1.36,2.89) | 0.0004 | 1.91 (1.31,2.80) | 0.0008 |
P for linear trend ++ | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||||
Number of NCPCs | ||||||||
(per additional NCPC) | 1.23 (1.16,1.30) | <0.0001 | 1.16 (1.09,1.23) | <0.0001 | 1.13 (1.06,1.20) | 0.0002 | 1.12 (1.05,1.20) | 0.0007 |
Any Non-Cancer Chronic Pain Condition (NCPC) ** | Alive at Follow-Up, No ADRD (Referent) | Alive at Follow-Up, Incident ADRD | Died before Follow-Up, Incident ADRD | Died before Follow-Up, No ADRD | ||||
---|---|---|---|---|---|---|---|---|
OR | p | OR (95% CI) | p | OR (95% CI) | p | OR (95% CI) | p | |
Model 1. Unadjusted model | 1.00 | - | 1.55 (1.34,1.78) | <0.0001 | 1.29 (1.03,1.62) | 0.029 | 1.25 (1.12,1.40) | <0.0001 |
Model 2. Adjusted for sociodemographics ¥ | 1.00 | - | 1.34 (1.16,1.55) | <0.0001 | 1.10 (0.87,1.40) | 0.42 | 1.21 (1.07,1.36) | 0.0024 |
Model 3. Also adjusted for lifestyle and chronic physical health conditions ¥¥ | 1.00 | - | 1.28 (1.11,1.49) | 0.0009 | 1.03 (0.79,1.34) | 0.8287 | 1.05 (0.93,1.18) | 0.4461 |
Model 4. Also adjusted for NSAID and opioid analgesic use | 1.00 | - | 1.26 (1.08,1.46) | 0.0026 | 0.99 (0.75,1.31) | 0.96 | 0.97 (0.85,1.10) | 0.60 |
NCPC Presence/Number | Fully Adjusted Model ¥ | Model ¥ + Mood Disorders § | Model ¥ + Sleep Disorders §§ | Model ¥ + Mood and Sleep Disorders | ||||
---|---|---|---|---|---|---|---|---|
OR (95% CI) | p | OR (95% CI) | p | OR (95% CI) | p | OR (95% CI) | p | |
Any NCPC vs. None ** | 1.25 (1.08,1.45) | 0.0032 | 1.17 (1.01,1.37) | 0.0388 | 1.20 (1.04,1.39) | 0.0155 | 1.18 (1.01,1.38) | 0.0336 |
Number of NCPCs | ||||||||
None (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | 1.00 (referent) | ||||
One | 1.23 (1.04,1.45) | 0.0179 | 1.19 (1.01,1.41) | 0.0408 | 1.20 (1.02,1.43) | 0.0311 | 1.17 (0.99,1.39) | 0.0594 |
Two | 1.20 (1.01,1.43) | 0.0435 | 1.13 (0.95,1.36) | 0.1722 | 1.16 (0.97,1.38) | 0.1008 | 1.11 (0.92,1.32) | 0.2713 |
Three | 1.34 (1.07,1.68) | 0.0122 | 1.22 (0.96,1.55) | 0.0962 | 1.25 (0.99,1.58) | 0.0589 | 1.17 (0.92,1.48) | 0.2112 |
Four or more | 1.91 (1.31,2.80) | 0.0008 | 1.57 (1.06,2.34) | 0.0255 | 1.66 (1.12,2.45) | 0.0113 | 1.41 (0.94,2.12) | 0.0941 |
p for linear trend++ | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||||
Number of NCPCs | ||||||||
(per additional NCPC) | 1.12 (1.05,1.20) | 0.0007 | 1.08 (1.01,1.16) | 0.027 | 1.09 (1.02,1.16) | 0.0101 | 1.06 (0.99,1.13) | 0.1001 |
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Khalid, S.; Sambamoorthi, U.; Innes, K.E. Non-Cancer Chronic Pain Conditions and Risk for Incident Alzheimer’s Disease and Related Dementias in Community-Dwelling Older Adults: A Population-Based Retrospective Cohort Study of United States Medicare Beneficiaries, 2001–2013. Int. J. Environ. Res. Public Health 2020, 17, 5454. https://doi.org/10.3390/ijerph17155454
Khalid S, Sambamoorthi U, Innes KE. Non-Cancer Chronic Pain Conditions and Risk for Incident Alzheimer’s Disease and Related Dementias in Community-Dwelling Older Adults: A Population-Based Retrospective Cohort Study of United States Medicare Beneficiaries, 2001–2013. International Journal of Environmental Research and Public Health. 2020; 17(15):5454. https://doi.org/10.3390/ijerph17155454
Chicago/Turabian StyleKhalid, Sumaira, Usha Sambamoorthi, and Kim E. Innes. 2020. "Non-Cancer Chronic Pain Conditions and Risk for Incident Alzheimer’s Disease and Related Dementias in Community-Dwelling Older Adults: A Population-Based Retrospective Cohort Study of United States Medicare Beneficiaries, 2001–2013" International Journal of Environmental Research and Public Health 17, no. 15: 5454. https://doi.org/10.3390/ijerph17155454