Pain as a Protective Factor for Alzheimer Disease in Patients with Cancer

SIMPLE SUMMARY: Alzheimer disease (AD) and cancer have been reported to be inversely correlated in epidemiological studies. However, the mechanism behind it is not clear. The aim of our retrospective study was to assess the 11 risk factors, including pain, for subsequent AD death in patients with cancer. We examined a SEER Research Plus population of 25,512 cases and 127,560 controls. We found that pain was related to lower AD risk in all subgroups except for digestive cancer. In addition, age, sex, race, number of in situ/malignant tumors, number of benign/borderline tumors, cancer site, cancer-directed surgery, radiation, chemotherapy and survival years were independent factors of AD risk in cancer patients. The risk factors varied by cancer site and race. This study demonstrated pain as a novel protective factor of AD and suggests the uniqueness of the digestive system in interacting with the central nervous system, which provide new perspectives for future studies. ABSTRACT: Objective: Alzheimer disease (AD) and cancer have been reported to be inversely correlated in incidence, but the mechanism remains elusive. Methods: A case-control study was conducted, based on the SEER (Surveillance, Epidemiology, and End Results) Research Plus data, to evaluate 12 factors in patients with cancer. Results: Severe pain was related to reduced AD risk, while older age at cancer diagnosis, female, longer survival years after tumor diagnosis, more benign/borderline tumors, less cancer-directed surgery, and more chemotherapy were associated with higher AD risk. In addition, patients of different races or with different cancer sites were associated with different risks of getting AD. Cases had a higher prevalence of severe pain than controls in all race and cancer site subgroups, except for in digestive cancer, where the result was the opposite. Conclusions: This study indicated pain as a novel protective factor for AD in patients with cancer. The mechanism behind it may provide new perspective on AD pathogenesis and AD-cancer association, which we discussed in our own hypothesis of the mechanism of pain action. In addition, digestive cancer pain had an opposite impact on AD risk from other cancer pains, which suggests the uniqueness of digestive system in interacting with the central nervous system.