Valacyclovir for Mild Cognitive Impairment

Inclusion Criteria:

1. Males and females ages 50-95. Females must be postmenopausal, defined as 12consecutive months without menstruation. (Patient Report)

2. Diagnosis of MCI (includes eMCI and lMCI by ADNI criteria)(NeuropsychologicalEvaluation)

3. Folstein Mini Mental State (MMSE) greater than or equal to 23/30. (Neuropsychological Evaluation)

4. Patient retains capacity to consent for him/herself. (Physician Evaluation)

5. At screening, patients must test positive for serum antibodies to HSV1 or HSV2. (Laboratory Tests)

6. Use of cholinesterase inhibitors or memantine is not required but will be permitted.If already prescribed, doses of these medications must be stable for 1 month priorto study entry. Patients are permitted to receive cholinesterase inhibitors and/ormemantine throughout the duration of the study. Any changes to the medication willbe documented in the participant research chart. Medications given for other medicalreasons, e.g., antidiabetic or anti-hypertensive medications, will not be alteredfor the purposes of this trial and the patient's primary physician may adjust suchmedications as medically indicated throughout the trial. Details of concomitantmedication use will be documented at all visits and will be available forstatistical analysis.(Patient Report)

7. Either PET amyloid scan positivity at screening, or prior CSF biomarker positive forAD. (Medical Records or through completing a PET scan as part of screening)

Exclusion Criteria:

1. Current clinical diagnosis of schizophrenia, schizoaffective disorder, otherpsychosis, bipolar disorder or current major depression by DSM-5 criteria. Priorhistory of major depression will not be exclusionary. (Physician Evaluation)

2. Active suicidal intent or plan based on clinical assessment. (SRMP Assessment byStudy Physician)

3. Current or recent (past 6 months) alcohol or substance use disorder (DSM-5criteria). (Physician Evaluation)

4. Current diagnosis of other major neurological disorders, including Parkinson'sdisease, multiple sclerosis,CNS infection, Huntington's disease, and amyotrophiclateral sclerosis. (Physician Evaluation)

5. Clinical stroke with residual clinical deficits. MRI findings of cerebrovasculardisease (small infarcts, lacunes, periventricular disease) in the absence ofclinical stroke with residual neurological deficits will not lead to exclusion. (Physician Evaluation)

6. Acute, severe, unstable medical illness. For cancer, patients with active illness ormetastases in the last 12 months will be excluded, but past history of successfullytreated cancer will not lead to exclusion. (Physician Evaluation)

7. Sitting blood pressure > 160/100 mm Hg. (Physician Evaluation)

8. Renal failure as determined by an estimated Glomerular Filtration Rate (GFR) < 44ml/min/1.73m2. (Laboratory Report)

9. Serum vitamin B12 levels below the normal range. (Laboratory Report)

10. Patients with thyroid stimulating hormone (TSH) levels above 4.94 mlU/L. (LaboratoryReport)

11. Use of benzodiazepines in lorazepam equivalent doses equal to or greater than 2 mgdaily. (Patient Report)

12. For MRI, metal implants and pacemaker, and claustrophobia such that the patientrefuses MRI. (Patient Report)

13. Radiation exposure in the prior 12 months that, together with 18F- Florbetapir willbe above the FDA annual radiation exposure threshold. (Patient Report and PhysicianEvaluation)

14. Severe vision or hearing impairment that would prevent the participant fromperforming the psychometric tests accurately. This will be a clinical determinationby the study physician without formal testing or audiometry.(Physician Evaluation)