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This study employed a multicenter, randomized controlled trial (RCT) design to evaluate the efficacy and safety of deep cervical lymphatic/lymph node-venous anastomosis combined with oral donepezil compared to donepezil monotherapy in patients with Alzheimer's disease and moderate dementia. Participants were randomized using a central randomization system with stratified block design, with the study center and age group (50-64 years, 65-80 years) as stratification factors. While study participants and surgical investigators could not be blinded due to the nature of the intervention, efficacy assessors and imaging specialists remained blinded to ensure the objectivity and reliability of the findings. The intervention group received deep cervical lymphatic/lymph node-venous anastomosis (detailed surgical procedure is specified in the protocol) in combination with oral donepezil (5-10 mg/day), while the control group received oral donepezil alone. The total treatment and follow-up period was 18 months, with assessments conducted at baseline, 1 week, 1, 3, 6, 12, and 18 months post-operation. These included neuropsychological evaluations (MMSE, MoCA, CDR, BADL, IADL, NPI, AES), neuroimaging (MRI, PET, ultrasound), fluid biomarker analyses (CSF and blood levels of Aβ, Tau, neuroinflammatory factors, etc.), and safety monitoring. The primary efficacy endpoint was the change in CDR-SB score at 12 months post-treatment. Secondary endpoints included changes in multiple cognitive scales, neuroimaging metrics, and biomarkers at 18 months. Safety indicators encompassed adverse event recording, vital signs, and laboratory tests.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cervical lymph vessel/node-venous anastomosis surgery combined with oral donepezil group | Experimental |
| |
| Oral donepezil group | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cervical lymph vessel/node-venous anastomosis surgery combined with oral donepezil | Procedure | Under total intravenous anesthesia, the patient is placed supine with the head turned and shoulders elevated. A transverse neck incision is made, the platysma is opened, and the external jugular vein and great auricular nerve are exposed and protected. Dissection proceeds along the sternocleidomastoid muscle and carotid sheath to create two lymphatic composite flaps: a lateral IIB/III flap rich in deep cervical lymph nodes and lymphatic vessels, and a medial IIA flap containing the angular lymph node. Both flaps are prepared to ensure continuous lymphatic fluid outflow. Revascularization is then performed by end-to-end anastomosis of the IIA flap to a branch of the common facial vein or external jugular vein, and end-to-side anastomosis of the IIB/III flap to the internal or external jugular vein. After the anastomosis is completed, the incision is sutured layer by layer for cosmetic purposes. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Clinical Dementia Rating-Sum of Boxes Score at Month 12 | The Clinical Dementia Rating-Sum of Boxes is a clinician-rated measure of dementia severity. The score ranges from 0 to 18, with higher scores indicating greater impairment and more severe dementia. The outcome measure is the change from baseline to Month 12. The scale will be administered face to face by trained evaluators blinded to treatment assignment, and results will be reviewed by an independent endpoint adjudication committee. | Baseline and Month 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Clinical Dementia Rating-Sum of Boxes Score at Month 18 | The Clinical Dementia Rating-Sum of Boxes score ranges from 0 to 18, with higher scores indicating greater dementia severity. The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Mini-Mental State Examination Score at Month 18 |
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Inclusion Criteria
Exclusion Criteria
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yixin Zhang | Contact | +86 13061775858 | zhangyixin6688@163.com | |
| Ke Li | Contact |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University | Shanghai | Huangpu | 200011 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | Kukreja-Pandey S, Al-Malak M, Ku Y, Duarte-Bateman D, Chen WF. D40. Effects of Lymphaticovenular Anastomosis in Contralateral Leg in Patients with Acquired Bilateral Leg Lymphedema. Plast Reconstr Surg Glob Open.2023;11(4S):81-82. | ||
| Background | 卢鸿瑞,谭云飞,谢庆平. 3D脱目镜下行颈深淋巴管-静脉引流术治疗老年认知障碍患者一例疗效初步观察. 中华显微外科杂志,2022,45(5):570-574. | ||
| 38934362 | Background | Jack CR Jr, Andrews JS, Beach TG, Buracchio T, Dunn B, Graf A, Hansson O, Ho C, Jagust W, McDade E, Molinuevo JL, Okonkwo OC, Pani L, Rafii MS, Scheltens P, Siemers E, Snyder HM, Sperling R, Teunissen CE, Carrillo MC. Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimers Dement. 2024 Aug;20(8):5143-5169. doi: 10.1002/alz.13859. Epub 2024 Jun 27. | |
| 34925100 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 29, 2026 |
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| Oral treatment with donepezil | Drug | After randomly assigned into the group, the study participants were given donepezil orally (the cervical lymph vessel/node-venous anastomosis surgery combined with oral donepezil group began to take donepezil orally on the first day after operation, and the oral donepezil group began to take donepezil after completing the baseline examination), once a day, before sleep, starting at 5 mg/day, and adjusted to 10 mg/day after 6 weeks; if not tolerated, it will be maintained at 5 mg/day, continued for 6 weeks, and then 10 mg/day will be attempted again, with continuous administration for 18 months. If research participants still cannot tolerate the high dose, they may be maintained at 5 mg/day for 18 months. |
|
The Mini-Mental State Examination assesses global cognitive function. The score ranges from 0 to 30, with higher scores indicating better cognitive function. The outcome measure is the change from baseline to Month 18. |
| Baseline and Month 18 |
| Change From Baseline in Montreal Cognitive Assessment Score at Month 18 | The Montreal Cognitive Assessment assesses cognitive function. The score ranges from 0 to 30, with higher scores indicating better cognitive function. The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in 18-item Apathy Evaluation Scale Score at Month 18 | The 18-item Apathy Evaluation Scale assesses apathy symptoms. The total score ranges from 18 to 72, with higher scores indicating more severe apathy. The outcome measure is the change from baseline to Month 18. Assessments will be performed by trained evaluators blinded to treatment assignment. | Baseline and Month 18 |
| Change From Baseline in Neuropsychiatric Inventory Total Score at Month 18 | The 12-item Neuropsychiatric Inventory assesses behavioral and psychological symptoms in dementia. For each domain, the domain score is calculated as frequency multiplied by severity. The total score ranges from 0 to 144, with higher scores indicating more severe neuropsychiatric symptoms. The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Basic Activities of Daily Living Score at Month 18 | The Basic Activities of Daily Living score is derived from six items of the Activities of Daily Living scale, including walking, eating, dressing, grooming, bathing, and toileting. Each item is scored from 1 to 4, and the total score ranges from 6 to 24, with higher scores indicating greater impairment in basic self-care ability. The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Instrumental Activities of Daily Living Score at Month 18 | The Instrumental Activities of Daily Living score is derived from eight items of the Activities of Daily Living scale, including using public transportation, cooking, doing housework, taking medication, doing laundry, shopping, using the telephone, and handling personal finances. Each item is scored from 1 to 4, and the total score ranges from 8 to 32, with higher scores indicating greater impairment in complex daily living ability. The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in PET Imaging Measures at Month 18 | Positron emission tomography (PET) will be used to assess cerebral amyloid and tau burden: Amyloid PET: Cerebral amyloid deposition will be quantified using the unitless standardized uptake value ratio (SUVR) and the standardized Centiloid scale. Higher SUVR and Centiloid values indicate greater amyloid deposition. Tau PET: Cerebral tau deposition will be quantified using the unitless standardized uptake value ratio (SUVR). Higher SUVR values indicate greater tau deposition. | Baseline and Month 18 |
| Change From Baseline in Brain Volumetric MRI Measures at Month 18 | Structural brain MRI will be used to measure gray matter volume (GMV), white matter volume (WMV), cerebrospinal fluid volume (CSFV), intracranial volume (ICV), white matter hyperintensity volume (WMHV), hippocampal volume (HippV), and frontal lobe volume (FronV). All volumes will be reported in milliliters (mL). The outcome measures are the changes in these MRI-derived volumes from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Glymphatic System-Related MRI Measures at Month 18 | MRI will be used to assess glymphatic system-related measures: perivascular space volume fraction in the whole brain, white matter, and basal ganglia (PVSVF-ALL, PVSVF-WM, and PVSVF-BG); free-water fraction in the whole brain, white matter, and basal ganglia (FW-ALL, FW-WM, and FW-BG); and diffusion tensor imaging analysis along the perivascular space indices for the left hemisphere, right hemisphere, and overall brain (ALPS-L, ALPS-R, and ALPS-ALL). PVSVF and FW are reported as unitless numerical fractions, and the ALPS indices are dimensionless. The outcome measures are the changes in these MRI-derived values from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Internal Jugular Vein Diameter on Ultrasound at Month 18 | Ultrasound will be used to measure the diameter of the internal jugular vein in the operative area. The diameter will be reported in millimeters. The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in External Jugular Vein Diameter on Ultrasound at Month 18 | Ultrasound will be used to measure the diameter of the external jugular vein in the operative area. The diameter will be reported in millimeters. The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Maximum Jugular Vein Flow Velocity on Ultrasound at Month 18 | Ultrasound will be used to measure the maximum flow velocity of the internal or external jugular vein in the operative area. Flow velocity will be reported in centimeters per second. The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Histopathological Findings in Intraoperatively Collected Lymph Node Tissue | Histopathological findings in lymph node tissue collected intraoperatively, when available, will be assessed using routine histopathological staining. | During surgery |
| Concentration of Phosphorylated Tau 217 in Intraoperatively Collected Lymphatic Fluid | The concentration of phosphorylated tau 217 (P-tau217) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Amyloid-Beta 42 in Intraoperatively Collected Lymphatic Fluid | The concentration of amyloid-beta 42 (Aβ42) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Phosphorylated Tau 181 in Intraoperatively Collected Lymphatic Fluid | The concentration of phosphorylated tau 181 (P-tau181) in lymphatic fluid collected intraoperatively, when available, will be measured （pg/ml). | During surgery |
| Concentration of Amyloid-Beta 40 in Intraoperatively Collected Lymphatic Fluid | The concentration of amyloid-beta 40 (Aβ40) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Neurofilament Light Chain in Intraoperatively Collected Lymphatic Fluid | The concentration of neurofilament light chain (NfL) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Glial Fibrillary Acidic Protein in Intraoperatively Collected Lymphatic Fluid | The concentration of glial fibrillary acidic protein (GFAP) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Interleukin-1 Alpha in Intraoperatively Collected Lymphatic Fluid | The concentration of interleukin-1 alpha (IL-1α) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Interleukin-1 Beta in Intraoperatively Collected Lymphatic Fluid | The concentration of interleukin-1 beta (IL-1β) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Interleukin-8 in Intraoperatively Collected Lymphatic Fluid | The concentration of interleukin-8 (IL-8) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Tumor Necrosis Factor Alpha in Intraoperatively Collected Lymphatic Fluid | The concentration of tumor necrosis factor alpha (TNF-α) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Interleukin-12 in Intraoperatively Collected Lymphatic Fluid | The concentration of interleukin-12 (IL-12) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Interleukin-6 in Intraoperatively Collected Lymphatic Fluid | The concentration of interleukin-6 (IL-6) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Interferon Gamma in Intraoperatively Collected Lymphatic Fluid | The concentration of interferon gamma (IFN-γ) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Interleukin-17A in Intraoperatively Collected Lymphatic Fluid | The concentration of interleukin-17A (IL-17A) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Interleukin-4 in Intraoperatively Collected Lymphatic Fluid | The concentration of interleukin-4 (IL-4) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Interleukin-10 in Intraoperatively Collected Lymphatic Fluid | The concentration of interleukin-10 (IL-10) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Interleukin-1 Receptor Antagonist in Intraoperatively Collected Lymphatic Fluid | The concentration of interleukin-1 receptor antagonist (IL-1ra) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Concentration of Transforming Growth Factor Beta in Intraoperatively Collected Lymphatic Fluid | The concentration of transforming growth factor beta (TGF-β) in lymphatic fluid collected intraoperatively, when available, will be measured (pg/mL). | During surgery |
| Change From Baseline in Cerebrospinal Fluid P-tau181 Level at Month 18 | The concentration of phosphorylated tau 181 (P-tau181) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid Total Tau Level at Month 18 | The concentration of total tau (T-tau) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid Aβ42 Level at Month 18 | The concentration of amyloid-beta 42 (Aβ42) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid Aβ40 Level at Month 18 | The concentration of amyloid-beta 40 (Aβ40) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid Aβ42/Aβ40 Ratio at Month 18 | The ratio of amyloid-beta 42 to amyloid-beta 40 (Aβ42/Aβ40) in cerebrospinal fluid will be reported as a unitless ratio. The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid BD-tau Level at Month 18 | The concentration of brain-derived tau (BD-tau) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid GFAP Level at Month 18 | The concentration of glial fibrillary acidic protein (GFAP) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid NfL Level at Month 18 | The concentration of neurofilament light chain (NfL) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid pTau217 Level at Month 18 | The concentration of phosphorylated tau 217 (pTau217) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid IL-1α Level at Month 18 | The concentration of interleukin-1 alpha (IL-1α) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid IL-1β Level at Month 18 | The concentration of interleukin-1 beta (IL-1β) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid IL-8 Level at Month 18 | The concentration of interleukin-8 (IL-8) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid TNF-α Level at Month 18 | The concentration of tumor necrosis factor alpha (TNF-α) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid IL-12 Level at Month 18 | The concentration of interleukin-12 (IL-12) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid IL-6 Level at Month 18 | The concentration of interleukin-6 (IL-6) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid IFN-γ Level at Month 18 | The concentration of interferon gamma (IFN-γ) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid IL-17A Level at Month 18 | The concentration of interleukin-17A (IL-17A) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid IL-4 Level at Month 18 | The concentration of interleukin-4 (IL-4) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid IL-10 Level at Month 18 | The concentration of interleukin-10 (IL-10) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid IL-1ra Level at Month 18 | The concentration of interleukin-1 receptor antagonist (IL-1ra) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Cerebrospinal Fluid TGF-β Level at Month 18 | The concentration of transforming growth factor beta (TGF-β) in cerebrospinal fluid will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma P-tau181 Level at Month 18 | The concentration of phosphorylated tau 181 (P-tau181) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma Total Tau Level at Month 18 | The concentration of total tau (T-tau) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma Aβ42 Level at Month 18 | The concentration of amyloid-beta 42 (Aβ42) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma Aβ40 Level at Month 18 | The concentration of amyloid-beta 40 (Aβ40) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma Aβ42/Aβ40 Ratio at Month 18 | The ratio of amyloid-beta 42 to amyloid-beta 40 (Aβ42/Aβ40) in plasma will be reported as a unitless ratio. The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma BD-tau Level at Month 18 | The concentration of brain-derived tau (BD-tau) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma GFAP Level at Month 18 | The concentration of glial fibrillary acidic protein (GFAP) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma NfL Level at Month 18 | The concentration of neurofilament light chain (NfL) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma pTau217 Level at Month 18 | The concentration of phosphorylated tau 217 (pTau217) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma IL-1α Level at Month 18 | The concentration of interleukin-1 alpha (IL-1α) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma IL-1β Level at Month 18 | The concentration of interleukin-1 beta (IL-1β) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma IL-8 Level at Month 18 | The concentration of interleukin-8 (IL-8) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma TNF-α Level at Month 18 | The concentration of tumor necrosis factor alpha (TNF-α) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma IL-12 Level at Month 18 | The concentration of interleukin-12 (IL-12) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma IL-6 Level at Month 18 | The concentration of interleukin-6 (IL-6) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma IFN-γ Level at Month 18 | The concentration of interferon gamma (IFN-γ) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma IL-17A Level at Month 18 | The concentration of interleukin-17A (IL-17A) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma IL-4 Level at Month 18 | The concentration of interleukin-4 (IL-4) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma IL-10 Level at Month 18 | The concentration of interleukin-10 (IL-10) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma IL-1ra Level at Month 18 | The concentration of interleukin-1 receptor antagonist (IL-1ra) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Change From Baseline in Plasma TGF-β Level at Month 18 | The concentration of transforming growth factor beta (TGF-β) in plasma will be measured in picograms per milliliter (pg/mL). The outcome measure is the change from baseline to Month 18. | Baseline and Month 18 |
| Background |
| Zhang S, Qiu Q, Qian S, Lin X, Yan F, Sun L, Xiao S, Wang J, Fang Y, Li X. Determining Appropriate Screening Tools and Cutoffs for Cognitive Impairment in the Chinese Elderly. Front Psychiatry. 2021 Dec 2;12:773281. doi: 10.3389/fpsyt.2021.773281. eCollection 2021. |
| 37467388 | Background | Xie Q, Louveau A, Pandey S, Zeng W, Chen WF. Rewiring the Brain: The Next Frontier in Supermicrosurgery. Plast Reconstr Surg. 2024 Feb 1;153(2):494e-495e. doi: 10.1097/PRS.0000000000010933. Epub 2023 Jul 18. No abstract available. |
| 33911285 | Background | Da Mesquita S, Papadopoulos Z, Dykstra T, Brase L, Farias FG, Wall M, Jiang H, Kodira CD, de Lima KA, Herz J, Louveau A, Goldman DH, Salvador AF, Onengut-Gumuscu S, Farber E, Dabhi N, Kennedy T, Milam MG, Baker W, Smirnov I, Rich SS; Dominantly Inherited Alzheimer Network; Benitez BA, Karch CM, Perrin RJ, Farlow M, Chhatwal JP, Holtzman DM, Cruchaga C, Harari O, Kipnis J. Meningeal lymphatics affect microglia responses and anti-Abeta immunotherapy. Nature. 2021 May;593(7858):255-260. doi: 10.1038/s41586-021-03489-0. Epub 2021 Apr 28. |
| 30046111 | Background | Da Mesquita S, Louveau A, Vaccari A, Smirnov I, Cornelison RC, Kingsmore KM, Contarino C, Onengut-Gumuscu S, Farber E, Raper D, Viar KE, Powell RD, Baker W, Dabhi N, Bai R, Cao R, Hu S, Rich SS, Munson JM, Lopes MB, Overall CC, Acton ST, Kipnis J. Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease. Nature. 2018 Aug;560(7717):185-191. doi: 10.1038/s41586-018-0368-8. Epub 2018 Jul 25. |
| 28862640 | Background | Louveau A, Plog BA, Antila S, Alitalo K, Nedergaard M, Kipnis J. Understanding the functions and relationships of the glymphatic system and meningeal lymphatics. J Clin Invest. 2017 Sep 1;127(9):3210-3219. doi: 10.1172/JCI90603. Epub 2017 Sep 1. |
| 26030524 | Background | Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Lee KS, Harris TH, Kipnis J. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015 Jul 16;523(7560):337-41. doi: 10.1038/nature14432. Epub 2015 Jun 1. |
| 37459141 | Background | Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, Sparks J, Wessels AM, Shcherbinin S, Wang H, Monkul Nery ES, Collins EC, Solomon P, Salloway S, Apostolova LG, Hansson O, Ritchie C, Brooks DA, Mintun M, Skovronsky DM; TRAILBLAZER-ALZ 2 Investigators. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. 2023 Aug 8;330(6):512-527. doi: 10.1001/jama.2023.13239. |
| 36449413 | Background | van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer LD, Iwatsubo T. Lecanemab in Early Alzheimer's Disease. N Engl J Med. 2023 Jan 5;388(1):9-21. doi: 10.1056/NEJMoa2212948. Epub 2022 Nov 29. |
| 27582220 | Background | Sevigny J, Chiao P, Bussiere T, Weinreb PH, Williams L, Maier M, Dunstan R, Salloway S, Chen T, Ling Y, O'Gorman J, Qian F, Arastu M, Li M, Chollate S, Brennan MS, Quintero-Monzon O, Scannevin RH, Arnold HM, Engber T, Rhodes K, Ferrero J, Hang Y, Mikulskis A, Grimm J, Hock C, Nitsch RM, Sandrock A. The antibody aducanumab reduces Abeta plaques in Alzheimer's disease. Nature. 2016 Sep 1;537(7618):50-6. doi: 10.1038/nature19323. |
| 26987701 | Background | Winblad B, Amouyel P, Andrieu S, Ballard C, Brayne C, Brodaty H, Cedazo-Minguez A, Dubois B, Edvardsson D, Feldman H, Fratiglioni L, Frisoni GB, Gauthier S, Georges J, Graff C, Iqbal K, Jessen F, Johansson G, Jonsson L, Kivipelto M, Knapp M, Mangialasche F, Melis R, Nordberg A, Rikkert MO, Qiu C, Sakmar TP, Scheltens P, Schneider LS, Sperling R, Tjernberg LO, Waldemar G, Wimo A, Zetterberg H. Defeating Alzheimer's disease and other dementias: a priority for European science and society. Lancet Neurol. 2016 Apr;15(5):455-532. doi: 10.1016/S1474-4422(16)00062-4. No abstract available. |
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| Jun 5, 2026 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 11, 2026 | Apr 12, 2026 | ICF_001.pdf |
| ID | Term |
|---|---|
| D000077265 | Donepezil |
| D013812 | Therapeutics |
| ID | Term |
|---|---|
| D007189 | Indans |
| D007192 | Indenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |
Not provided
Not provided