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Cancer-related Lymphedema and Alzheimer's Disease Development after ALND
Stav Brown, MD, Felix Klimitz, MD, Siba Haykal MD PhD, Bohdan Pomahac, MD
1. Yale school of Medicine, New haven, CT, United States.
Background: Emerging evidence suggests that impaired cervical lymphatic drainage contributes to the accumulation of amyloid-beta and the pathogenesis of Alzheimer's disease (AD). While axillary lymph node dissection (ALND) is a common cause of cancer-related lymphedema, its potential relationship to AD has not been previously explored.
Methods: We analyzed all female patients who underwent ALND at a tertiary cancer center from 2013 to 2024. Demographic and clinical data were collected, including lymphedema diagnosis and AD onset. A multivariate regression analysis and Propensity Score Matching were used to assess risk factors for AD after ALND and evaluate the relationship between lymphedema and AD development.
Results: Of the 15,666 patients, 2,535 (16.2%) developed lymphedema, with a mean onset of 20.5 months post-ALND. Among the 8,095 patients aged 60 or older, 243 (3.0%) were diagnosed with AD. Significant independent predictors of AD included older age at ALND (OR = 1.11, p < 0.001), cerebrovascular disease (OR = 1.63, p = 0.002), and preexisting depression (OR = 3.56, p < 0.001). African American race was associated with increased risk (OR = 1.87, p = 0.005), as was Hispanic/Latino ethnicity (OR = 2.20, p = 0.002). Importantly, a diagnosis of lymphedema was associated with a significantly lower risk of developing AD (OR = 0.34, p = 0.001).
Conclusion: This is the first and largest study to investigate the relationship between lymphedema and AD following ALND. Further research is warranted to explore whether therapeutic interventions for lymphedema or compensatory enhancements in central lymphatic drainage caused by extremity lymphedema may enhance clearance and contribute to reduced AD risk.
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