The goal of this clinical trial is to learn if the drug Egb761, produced from Ginkgo Biloba extract, works to improve the blood level of a biomarker of Alzheimer's disease, called phosphorylated-tau217 (p-tau217), which serves as a biomarker for disease activity in the brain. The main questions it aims to answer are:

Does drug Egb761 lower the plasma level of p-tau217 in patients with mild cognitive impairment? Does drug Egb761 improve cognitive and behavioral functions in these patients? Does Egb761 affect the blood levels of neurofilament-light (Nfl) and glial-fibrillary-acidic-protein (GFAP), which serve as additional biomarkers for brain disease activity?

Participants will:

Take Egb761 twice daily for 6 months Visit the clinic once every 3 months for checkups and tests Keep a diary of their symptoms

Participating center: A single-center trial performed at Hadassah - Hebrew University Medical Center in Jerusalem, Israel. The investigators have vast experience in performing full medical and neuropsychological evaluations, and in performing clinical trials in patients with cognitive decline. Patients will be recruited via the cognitive Neurology clinics at the Hadassah Ein-Kerem campus, Hadassah Mount Scopus campus, and Merhav out-patient clinic for cognitive Neurology, which is associated and operated by Hadassah Neurologists.

Patient recruitment: 50 patients with mild cognitive impairment (MCI) will be recruited, according to its accepted definition. Patients with MCI will undergo standard evaluation, including brain imaging (MRI / CT), thyroid function tests, Vitamin B12, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) to rule out other causes of cognitive decline.

The investigators expect that approximately 70% of recruited patients will display increased plasma p-tau217 level, indicating MCI of Alzheimer's type.

Clinical and neuropsychological evaluation will include: (1) Full demographic data (age, gender, education level and occupation, family status, ethnicity and country of origin); (2) Clinical data on risk factors (metabolic/ cardiovascular risk factors - heart disease, diabetes, hypertension, hyperlipidemia; Infectious/ inflammatory risk factors - periodontal disease, systemic infections, systemic inflammatory conditions; Lifestyle factors - smoking, alcohol consumption, sleeping disorder, physical activity; and Mental factors - anxiety and depression, cognitive activity); (3) MoCA (in Hebrew version); (4) Mild Behavioral Impairment checklist (MBI-C), or Neuropsychiatric Inventory (NPI) questionnaire (in Hebrew version); (5) ADL and iADL questionnaire; (6)Trail making test -B (TMT-B); Word fluency test.

Determination of blood biomarkers: Venous blood will be drawn upon recruitment in a tube containing EDTA to prevent clotting. The blood will be centrifuged at 1200 rpm for 5 minutes, and plasma stored in -80°C, within two hours of drawing the blood sample. The samples will be stored in a temperature-controlled and monitored freezer, until delivery in dry ice to the central lab (Prof. Ben-Hur's lab at the Ein-Kerem campus) for determination of biomarkers. Blood samples that were collected at recruitment will be tested for p-tau217 level, neurofilament light and GFAP. The baseline p-tau217 will serve as a reference value for monitoring individual response to therapy, as well as the group trend in the other biomarkers.

Treatment: All patients will receive Cerebonin (Egb761) 240mg per day, by tablets of 120mg, taken twice daily.

Follow-up: After initiation of treatment, patients will be invited for follow-up visits at 3 months and 6 months. Clinical data (risk factor assessment), MoCA, MBI-C, iADL and plasma p-tau217 level will be evaluated in each visit. The investigators will evaluate total MoCA score, as well as its breakdown into cognitive domains (attention, executive, memory (both free and cued / recognition recall), visuospatial, language, and orientation). One point is added if the subject has ≤12 years of education.

Evaluating response to therapy: (1) In patients with high baseline plasma p-tau181 level, the investigators will compare pre- and post-treatment plasma p-tau-217 levels (Δp-tau). Since plasma p-tau217 is considered a biomarker of active brain disease, a reduction in its level will suggest a disease-modifying therapeutic effect; (2) The investigators will examine the trend in group averages of neurofilament and GFAP, as additional disease biomarkers. (3) The investigators will determine the symptomatic clinical response according to improvement in MoCA, MBI-C/NPI, TMT-B and ADL/iADL scores after 3 and 6 months of treatment; (4) The investigators will compare the treatment effect in MCI patients with high- versus normal- plasma p-tau217 levels (eg. in MCI of AD type versus non-AD type); (5) The investigators will examine the association between clinical improvement and change in the plasma level of biomarkers.

Inclusion Criteria:

• Mild cognitive impairment, as defined by MoCA score of 19-25.
• Preserved instrumental activities of daily life (iADL).
• Clinical impression of MCI of AD type, and lack of major medical and neurological conditions, as detailed in the exclusion criteria.

Exclusion Criteria:

• Extrapyramidal signs, existence of multi-infract dementia, or Fronto-Temporal dementia, according to clinical impression by treating cognitive Neurologist.
• Active cancer, severe cardio-pulmonary disease or other medical condition which negatively affects ability to evaluate patients and complete follow-up.
• Inability to sign an informed consent due to psychiatric or dementing condition.
• Hypersensitivity to any ingredient of the study medication.

We plan to share IPD on cognitive, behavioral, and biomarker data without personal identification, as required by the IRB upon completion of the trial.