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Cognitive Impairment as a Manifestation of Primary Lymphedema: Evidence of Systemic Brain-Lymphatic Dysfunction and Its Potential Reversal with Surgery
Shih-Lun Lo, Agata Debowska, Melis Salman, David Chon Fok Cheong, Sonia Kukreja-Pandey, Wei F Chen
Cleveland Clinic
2025-01-10
Presenter: Melis Salman
Affidavit:
Represents original work of the fellows based on my patients, not previously published or presented
Director Name: Wei F. Chen
Author Category: Fellow Plastic Surgery
Presentation Category: Clinical
Abstract Category: General Reconstruction
PURPOSE: Lymphedema and cognitive impairment were once thought to be unrelated. However, recent discoveries of brain lymphatics and the systemic nature of primary lymphedema suggest a possible connection. Given frequent patient reports of cognitive impairment, this study investigates the relationship between primary lymphedema and cognitive dysfunction.
METHODS: We assessed cognitive function in 81 patients with primary lymphedema (67 females, 14 males; mean age 45) using the Montreal Cognitive Assessment (MoCA) and Brain Fog Scale (BFS). A comparative analysis was conducted against a historical control group of 1,046 healthy individuals. A subgroup analysis compared cognitive scores of patients who underwent lymphatic reconstruction (n=12) with those who did not (n=69). Statistical differences between groups were evaluated using independent t-tests.
RESULTS:Primary lymphedema patients had an average BFS score of 28.10�18.92 and a mean MoCA score of 27.92�2.28. Compared to controls, they showed significantly higher brain fog symptoms, including mental fatigue (10.58�5.44 vs. 8.62�4.63, p=0.0022), impaired cognitive acuity (10.57�8.44 vs. 7.81�6.18, p=0.0050), and confusion (6.95�6.56 vs. 5.18�5.71, p=0.0203). Patients with subjective cognitive complaints (n=21) had significantly higher BFS scores across all domains than those without (p<0.0001). Furthermore, patients who underwent lymphatic surgery reported lower brain fog symptoms, particularly in cognitive acuity (6.25�5.22 vs. 11.32�8.69, p=0.011) and total BFS score (19.75�11.87 vs. 29.55�19.59, p=0.027).
CONCLUSION: This study identifies a significant correlation between primary lymphedema and cognitive impairment. Post-surgical cognitive improvements suggest a mechanistic link between lymphatic function and cognitive performance, emphasizing the systemic nature of lymphedema and the necessity for cognitive assessments in affected patients.
