Linking Lymphedema, Chronic Inflammation, Oxidative Stress, Alzheimer Disease, and Potential Role of Lymphaticovenous Anastomosis

BACKGROUND: Lymphedema and Alzheimer disease (AD) share common mechanisms involving oxidative stress and chronic inflammation. However, the link between these 2 conditions and the impact of lymphaticovenous anastomosis (LVA) has not been fully explored. This study aimed to evaluate their association by examining changes in AD biomarkers, inflammatory cytokines, and oxidative stress markers before and after LVA.

METHODS: Twenty-four patients with unilateral lower limb lymphedema who underwent LVA as primary treatment and 18 healthy controls were recruited. Exclusion criteria included previous LVA, liposuction, or excisional surgery. Venous blood samples were obtained before and 1 month after LVA.

RESULTS: After matching, 15 patients remained in each group. The lymphedema group had significantly elevated levels of t-tau (p < 0.001), amyloid beta (Aβ) 1-40 ( P = 0.033), Aβ 1-42 ( P = 0.033), Aβ 1-42 × t-tau ( P < 0.001), and Aβ 1-42/Aβ 1-40 ratio ( P = 0.021) compared with controls. One month post-LVA, there were significant reductions in t-tau ( P = 0.007) and Aβ 1-42 × t-tau ( P = 0.002), and a notable increase in brain-derived neurotrophic factor ( P = 0.006). Post-LVA samples also showed significant improvements in antioxidative enzymes, antioxidant capacity, and reductions in lipid peroxidation. Inflammatory cytokine levels were also significantly reduced, indicating decreased oxidative stress and inflammation. The median follow-up period was 6.3 months.

CONCLUSIONS: Findings suggest a possible association between lymphedema and increased AD risk possibly linked to elevated oxidative stress and inflammation. LVA may modulate this risk by reducing AD biomarkers and systemic inflammation/oxidative stress, supporting further investigation into its neuroprotective potential.