Association of Cancer with Alzheimer's Disease and related Dementias among older adults with chronic pains: TriNetX analysis with Multi-institutional Electronic Health Records

Introduction

Recent retrospective cohort studies have reported that non-cancer chronic pain, specifically non-cancer pain conditions (NCPCs), are associated with an increased risk of Alzheimer's disease and related dementias (ADRD) in older adults. However, a recent case-control study found that cancer-induced pain had a protective association with ADRD, suggesting that cancer pain's association with ADRD is inconclusive. Therefore, we analyzed the association of cancer with ADRD among older adults with chronic pain.

Methods

We adopted a retrospective cohort analysis. The cohort consisted of older adults with chronic pain in 2016 and 2017. The data used in this study is from the TriNetX Research Network, which provided access to electronic medical records (diagnoses, procedures, medications, and laboratory values) for patients from 64 healthcare organizations (HCOs). A propensity score-matched analysis of cancer and non-cancer patients used age, sex, race/ethnicity, surgery, factors influencing health status and contact with health services; endocrine, nutritional, and metabolic diseases; diseases of the circulatory system; nervous system; digestive system; musculoskeletal system and connective tissue; and mental, behavioral and neurodevelopmental disorders. The outcome variable was ADRD incidence, which occurred at least one year after the first chronic pain diagnosis.

Results

Before matching, among older adults with cancer, there were 212,739 and 465,316 with and without cancer, respectively. The 3-year cumulative incidence of ADRD was 2.97% (N = 6320) in the cancer group and 1.96% (N = 9096) in the non-cancer group. After propensity matching, there were 195289 participants in both groups. The cumulative incidence of ADRD was 2.79% (N = 5457) in the cancer group and 2.62% (N = 5124) in the non-cancer group (Risk Ratio = 1.07, 95% CI: 1.02-1.10). Secondary analysis of ADRD incidence in adults who died did not reveal a significant association between cancer with ADRD.

Conclusion

Our research has found that cancer is not associated with the risk of ADRD among patients with chronic pain. Our study estimates of ADRD incidence are lower than the national rates, suggesting the limitations of electronic health records in capturing true ADRD incidence.

The study's findings must be interpreted in the context of the study's strengths and limitations. For example, data were from 64 HCOs, and the study did not adjust for case-mix or practice differences. In addition, the study is limited to those seeking care in these HCOs and may have missed care obtained outside of these organizations. Thus, our estimates of ADRD incidence are substantially lower than the national ADRD incidence. Nevertheless, the study's strengths are the use of multi-institutional electronic health records, large numbers of cases and controls, and the ability to conduct propensity score-matched analysis with a comprehensive list of risk factors.

Keywords: Dementia, Alzheimer's disease, and Related Disorders, Cancer, Chronic Pain, EHR