The goal of this clinical trial is to evaluate the safety and efficacy of vagus nerve stimulation (VNS) for treating Alzheimer's disease (AD) in patients aged 50-80 years with mild cognitive impairment to moderate Alzheimer's disease. The main questions it aims to answer are: Is the change from baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) score at 6 months post-randomization better in the VNS group compared to the sham stimulation group? Is the change from baseline in scores of other cognitive function, neuropsychiatric symptom, or activities of daily living scales at 6 months post-randomization better in the VNS group compared to the sham stimulation group? Researchers will compare the group receiving vagus nerve stimulation (active VNS group) and the group receiving sham vagus nerve stimulation (sham VNS group) to see if VNS is more effective in improving cognitive function, neuropsychiatric symptoms, or activities of daily living. Participants will: Undergo screening assessments (including medical history, physical exams, cognitive and behavioral scale assessments, imaging, etc.). Undergo surgery for VNS device implantation. Be randomized to either the active VNS or sham VNS group and receive the corresponding stimulation treatment for 6 months (while continuing standard AD medication). Attend multiple follow-up visits during the study (baseline, randomization day, 3 months, and 6 months post-randomization) for clinical scale assessments. Potentially provide biological samples (blood, CSF) and undergo additional auxiliary examinations (e.g., MRI, EEG, PET) at specific time points.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
74
After randomization, VNS is performed for 6 months. The stimulation parameters will be 30 Hz and 250 μs, the maximum tolerable current is selected according to the patients' adverse reactions (dizziness, palpitations, abnormal sensations, local pain, etc.), and the recommended treatment intensity is 0.8 mA.
After randomization, sham vagus nerve stimulation VNS treatment is performed for 6 months. The stimulation parameters will be 30 Hz, 250 μs, and the treatment intensity will be 0 mA.
Beijing Tiantan Hospital
Beijing, China
RECRUITINGChange From Baseline in ADAS-Cog 14 Score
Change from baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 14-item total score. The ADAS-Cog assesses the severity of cognitive symptoms of Alzheimer's disease. Higher scores indicate greater cognitive impairment. Change is calculated as the score at a given timepoint minus the score at baseline.
Time frame: Baseline, 6 Months Post-randomization
Change From Baseline in MMSE Score
Change from baseline in the Mini-Mental State Examination (MMSE) score. Assesses global cognitive function. Scale ranges from 0 to 30; higher scores indicate better cognitive function. Change = Score at Timepoint - Score at Baseline.
Time frame: Baseline, 6 Months Post-randomization
Change From Baseline in AVLT Scores
Change from baseline in the Auditory Verbal Learning Test (AVLT) scores. Assesses verbal learning and memory. Key sub-scores assessed include immediate recall (sum of trials 1-5) and delayed recall. Scale ranges from 0 to 84; higher scores indicate better cognitive function.Change = Score at Timepoint - Score at Baseline.
Time frame: Baseline, 6 Months Post-randomization
Change From Baseline in CDR-SB Score
Change from baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) score. Assesses dementia severity across 6 domains (Memory, Orientation, Judgment \& Problem Solving, Community Affairs, Home \& Hobbies, Personal Care). Scores range from 0 to 18; higher scores indicate greater impairment. Change = Score at Timepoint - Score at Baseline.
Time frame: Baseline, 6 Months Post-randomization
Change From Baseline in CDR-GS Score
Change from baseline in the Clinical Dementia Rating - Global Score (CDR-GS). Provides an overall dementia severity stage (0=Normal, 0.5=Questionable, 1=Mild, 2=Moderate, 3=Severe) based on cognitive and functional performance. Change = Score at Timepoint - Score at Baseline.
Time frame: Baseline, 6 Months Post-randomization
Change From Baseline in HAMA Score
Change from baseline in the Hamilton Rating Scale for Anxiety (HAMA) total score. Assesses the severity of anxiety symptoms across 14 items. Higher scores indicate greater anxiety. Change = Score at Timepoint - Score at Baseline.
Time frame: Baseline, 6 Months Post-randomization
Change From Baseline in MAES Score
Change from baseline in the Modified Apathy Evaluation Scale (MAES) score. Assesses the severity of apathy. Higher scores indicate greater apathy. Change = Score at Timepoint - Score at Baseline.
Time frame: Baseline, 6 Months Post-randomization
Change From Baseline in ADCS-ADL Score
Change from baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Inventory score. Assesses patient functional ability in activities of daily living based on caregiver report. Higher scores indicate better functional ability. Change = Score at Timepoint - Score at Baseline.
Time frame: Baseline, 6 Months Post-randomization
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