{
  "abstract": "Background The glymphatic system facilitates clearance of interstitial solutes from the central nervous system, including amyloid-β and tau, and dysfunction of this pathway has been increasingly implicated in neurodegenerative disease. Experimental studies demonstrate that interruption of cervical lymphatic drainage accelerates amyloid deposition, neuroinflammation, and memory impairment. In humans, cervical lymph node dissection and radiotherapy performed during treatment for head and neck malignancy may disrupt glymphatic outflow, while emerging reports describe deep cervical lymphaticovenous anastomosis (dcLVA) as a potential intervention to augment lymphatic drainage in patients with Alzheimer’s disease.Objective To systematically review the clinical evidence linking cervical lymphatic interventions, both disruptive and reconstructive, with cognitive outcomes in humans.Methods PubMed and Embase were queried for human studies evaluating cognitive outcomes following cervical lymph node dissection, head and neck radiotherapy, or lymphaticovenous anastomosis. Two reviewers independently screened studies and extracted data on study design, patient population, cognitive outcomes, and adverse events. Quality was assessed using a custom five-domain rubric. The review was conducted in accordance with PRISMA 2020 guidelines.Results Twelve studies met inclusion criteria, comprising over 24,000 patients. Six studies evaluated cognitive outcomes following cervical lymphatic disruption: population-based cohorts demonstrated 1.9-fold increased dementia risk following head and neck cancer treatment, while prospective studies documented multi-domain cognitive impairment in 25-38% of patients. Chao et al. uniquely demonstrated that surgical lymph node dissection extent, rather than radiotherapy, was most strongly associated with dementia risk, with bilateral dissections conferring higher risk than unilateral procedures (p = 0.016). Six studies evaluated dcLVA in 236 Alzheimer’s disease patients. MMSE responder rates ranged from 61.5% to 83.3%, with the largest cohort (n = 139) demonstrating sustained improvement through 6-month follow-up. Adverse events were rare (1.7%) and mild. However, no study included a control group, outcome measures were heterogeneous, follow-up ranged from one week to six months, and all dcLVA studies originated from a single region.Conclusions Preliminary evidence suggests that cervical lymphatic disruption through oncologic treatment is associated with increased dementia risk, while dcLVA shows early promise in stabilizing cognition in Alzheimer’s disease. The consistent direction of effect and favorable safety profile support continued investigation. However, the absence of controlled trials, geographic homogeneity, and short follow-up represent critical limitations. Randomized controlled trials with standardized cognitive metrics are required to establish whether surgical modulation of cervical lymphatic drainage can alter the trajectory of neurodegenerative disease.Disclosures A. Goyal: None. V. Jaikumar: None. A. Siddiqui: None.Abstract E-152 Table 1Clinical characteristics following cervical lymphatic reconstructionLiXieChenTangMaFuYear202420252025202520252026CountryChinaChinaChinaChinaChinaChinaDesignCase reportCase reportProspective cohortProspective cohortRetrospective cohortProspective cohortN enrolled11262841139MMSE responder percentNANA61.564.383.3NRFollow up weeks416411224N ae events002020AE descriptionNANATransient arm elevation difficultyNo major complications reportedDelirium (1); Urinary retention (1)None reportedQuality score114354Abstract E-152 Table 2Clinical characteristics following cervical lymphatic disruptionChao 2024Lee 2023Chen JH 2015Zer 2018Chow 2024Penn 2021CountryTaiwanSouth KoreaTaiwanCanadaHong KongTaiwanDesignRetrospective cohortRetrospective cohortRetrospective cohortProspective cohortCross-sectionalRetrospective cohortN Enrolled251576 HNC; 2,304 controls2013580 patients; 40 controls190594 NPC; 2,376 controlsMean Age (years)66.6NR53NRNRNRInterventionCLNDHNC diagnosis ± treatmentRT ± chemotherapy for HNCDefinitive (chemo)radiotherapy for HNCIMRT for nasopharyngeal carcinomaRT for nasopharyngeal carcinomaFollow-up8.6 years (median)NRUp to 10 years24 months7 years (median)Up to 15 yearsCognitive Outcome measureDementia diagnosis (ICD codes)AD diagnosis (claims data)Dementia diagnosis (registry)Neurocognitive battery (6 domains)MoCA + 8-domain batteryDementia diagnosis (registry)Key Cognitive FindingsDementia incidence 0.7/100 patient-years; cumulative incidence 10.34%; bilateral/extensive dissection higher risk (p=0.016)AD incidence 14.92 vs 9.77/1000 person-years in HNC vs controls; higher risk in females and middle-aged patientsRT ± CT: HR 1.92 (95% CI 1.14-3.24) for dementia; dose >66.6 Gy HR 1.69; younger patients at highest risk38% global cognitive impairment at 24 months vs 0% controls; decline in memory, executive function, intellectual capacity25.3% impaired MoCA; 79.4% impaired ≥1 domain; verbal memory, processing speed, executive function most affectedDementia 6.57% vs 4.42%; adjusted HR 1.91 (95% CI 1.42-2.51)Quality Score444544",
  "authors": [
    {
      "affiliations": [
        "Department of Neurosurgery, Albany Medical Center, Albany, NY"
      ],
      "name": "A Goyal"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, University at Buffalo, Buffalo, NY"
      ],
      "name": "V Jaikumar"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, University at Buffalo, Buffalo, NY"
      ],
      "name": "A Siddiqui"
    }
  ],
  "title": "E-152 Surgical disruption of glymphatic pathways and cognitive impairment: a systematic review and descriptive analysis",
  "uid": "6cee2fe1-56e7-59b2-970d-e3715f9650ee"
}