{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:23:42Z","timestamp":1792268622385,"version":"4.4.0"},"reference-count":81,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Alzheimer's disease (AD) is a common neurodegenerative disorder with limited treatment options. Recent discoveries of the glymphatic system and meningeal lymphatic vessels (MLVs) have highlighted their critical role in clearing metabolic waste\u2014including amyloid beta and tau proteins\u2014from the brain. Dysfunction of these systems contributes to AD pathogenesis by impairing the clearance of neurotoxic proteins. Deep cervical lymphaticovenous anastomosis (dcLVA) is an innovative microsurgical technique designed to enhance cerebral waste drainage by anastomosing deep cervical lymphatic channels to adjacent veins. This narrative review synthesizes current evidence on the mechanisms, applications, and emerging perspectives of dcLVA for AD. Early studies suggest potential short\u2010term improvements in cognitive scores and neuroimaging biomarkers after surgery, with an acceptable safety profile. However, the evidence is limited to small prospective cohorts and case reports, underscoring the need for larger, randomized controlled trials to validate its efficacy and long\u2010term benefits. dcLVA represents a promising surgical intervention for select patients, particularly those with moderate\u2010to\u2010severe AD who have failed conventional pharmacotherapy, but it requires careful patient selection and further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>This review proposes deep cervical lymphaticovenous anastomosis (dcLVA) as a mechanism driven surgery that may enhance clearance of amyloid beta (A\u03b2) and tau through the brain, meningeal, and deep cervical drainage pathways.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Early human evidence from a single arm cohort and case reports suggests short term cognitive and imaging signals with acceptable perioperative safety.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>dcLVA is not recommended as a first line option for early Alzheimer's disease (AD) and may be considered for moderate to severe AD or for patients who are refractory to pharmacotherapy and have objective evidence of drainage impairment.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Standardized patient selection and longitudinal imaging and biomarker monitoring are recommended, including A\u03b2 and tau positron emission tomography (PET), diffusion tensor imaging (DTI) analysis along the perivascular space, and cerebrospinal fluid (CSF) or plasma panels.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Systemic safety remains an important uncertainty, and future trials should include longitudinal surveillance of hepatic, renal, and hematologic function.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Multicenter randomized controlled trials (RCTs) are urgently needed with 12 month Clinical Dementia Rating Sum of Boxes (CDR SB) as a primary endpoint, transparent reporting, and evaluation of combination strategies with anti A\u03b2 therapies.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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Guangzhou Institute of Respiratory Health the First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery the First Affiliated Hospital of Guangdong Pharmaceutical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Qingyuan Hospital (Qingyuan People's Hospital) Guangzhou Medical University  Qingyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Qingyuan Hospital (Qingyuan People's Hospital) Guangzhou Medical University  Qingyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2468\u20102667(21)00249\u20108"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.16150\/j.1671\u20102870.2024.03.001"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232213954"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa013128"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3233\/jad\u2010132690"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD001190.pub3"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003748"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142290"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14432"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29738"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10092261"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010024\u201005225\u2010z"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24271"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100368\u20108"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104987"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673\u20105374.230299"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010024\u201000691\u20103"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13789"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241224"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax5440"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201022354\u20102"},{"key":"e_1_2_12_24_1","first-page":"570","article-title":"Preliminary 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