Neurology
The Effects of Cancer on Alzheimer’s Disease and Related Dementia Risk by Type, Stage, and Treatment: The Multiethnic Cohort Study Gina Nam* Gina Nam Unhee Lim Song-Yi Park Yingyan Wu L. Paloma Rojas-Saunero Zuo-Feng Zhang Elizabeth Rose Mayeda
Background: Most research on cancer and subsequent Alzheimer’s disease and related dementias (ADRD) has treated cancer as homogeneous. Given cancer heterogeneity, effects on ADRD risk may vary.
Methods: The Multiethnic Cohort Study includes Black, Japanese American, Latino, Native Hawaiian, and White adults aged 45-75 at baseline in 1993. We estimated total and controlled direct effects of incident cancer on ADRD risk (RR) over 26 years (censored by 2019) using inverse probability weighting. We used the Aalen-Johansen estimator to estimate total effects (including paths mediated by death) and the Kaplan-Meier estimator to estimate controlled direct effects (eliminating paths mediated by death). Stratified analyses were conducted by cancer type, stage, and initial treatment.
Results: The study included 104,258 participants (74% non-White; 55% female), with 24,083 incident cancer identified from SEER tumor registries and 23,147 incident ADRD subsequently identified from Medicare claims. The five most common cancers were prostate (24%), breast (17%), colorectal (12%), lung (10%), and non-Hodgkin lymphoma (4.9%). Of the cancer cases, 56% were diagnosed at early stages and 58% received surgery for initial treatment. Total effect RRs for ADRD ranged from 0.19 (95% CI: 0.15-0.28) for lung cancer to 1.02 (0.89-1.06) for breast cancer. Controlled direct effect RRs ranged from 1.09 (0.99-1.21) for endometrium cancer to 1.56 (1.47-1.84) for stomach cancer. For late-stage cancers, total and controlled direct effect RRs for ADRD were 0.42 (0.39-0.46) and 1.29 (1.26-1.41), respectively. Among initial treatments, chemotherapy had the greatest reduction in total effect (RR 0.43; 0.39-0.47), while immunotherapy had the highest controlled direct effect (RR 1.44; 1.18-1.67) compared to other treatments.
Conclusions: Specific cancer characteristics influence the effects of incident cancer on ADRD risk, underscoring the importance of considering cancer heterogeneity in related research.