Is Cerebonin (Egb761) a Disease-modifying Therapy in Mild Cognitive Impairment

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.