Fornix and NbM as Targets of Stimulation In Alzheimer's Disease

A Randomized Controlled Study of 12 Months to Evaluate the Safety and Efficacy of Deep Brain Stimulation(DBS) to the Fornix & Meynert Nucleus(NbM) in Patients With Mild to Moderate Alzheimer's Disease(AD)

The primary goal of this study is to evaluate the efficacy and safety of the DBS to the fornix/NbM among patients who are diagnosed as AD according to a series of evaluations including cerebrospinal fluid (CSF) biomarkers and molecular imaging examinations; The secondary goal is to compare the efficacy among the two treatment groups of different targets.

Inclusion Criteria:

1. Subjects with informed consent;
2. 45-75 years of age;
3. At least 6 years of education;
4. AD according to the National Institute on Aging and the Alzheimer's Association (NIA-AA) guidelines (McKhann et al., 2011);
5. Clinical Dementia Rating Scale (CDR): 1.0-2.0;
6. Positive findings with amyloid PET imaging;
7. Stable prescription of donepezil (5mg, qd) for at least 3 months, and without any intentions to modify the dosage during the observation period.

Exclusion Criteria:

1. Fazekas scale>2;
2. Neuropsychiatric inventory (NPI) total score ≥10, or any subdomain≥4；
3. Modified Hachinski ischemic score>4；
4. Young Mania Rating Scale>11(Young, Biggs, Ziegler, & Meyer, 1978);
5. Any suicidal tendencies in recent 2 years;
6. Cornell Scale for Depression and Dementia>10;
7. Familial AD;
8. Abnormal brain structural magnetic resonance imaging (MRI) scan, including hydrocephalus, stroke, structural lesions, etc. that would potentially confound the outcome;
9. Surgical history of the central nervous system;
10. Severe cardiovascular/pulmonary disorders.