Valacyclovir for Mild Cognitive Impairment

Inclusion Criteria:

1. Males and females ages 50-95. Females must be postmenopausal, defined as 12 consecutive months without menstruation. (Patient Report)
2. Diagnosis of MCI (includes eMCI and lMCI by ADNI criteria)(Neuropsychological Evaluation)
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 prior to study entry. Patients are permitted to receive cholinesterase inhibitors and/or memantine throughout the duration of the study. Any changes to the medication will be documented in the participant research chart. Medications given for other medical reasons, e.g., antidiabetic or anti-hypertensive medications, will not be altered for the purposes of this trial and the patient's primary physician may adjust such medications as medically indicated throughout the trial. Details of concomitant medication use will be documented at all visits and will be available for statistical analysis.(Patient Report)
7. Either PET amyloid scan positivity at screening, or prior CSF biomarker positive for AD. (Medical Records or through completing a PET scan as part of screening)

Exclusion Criteria:

1. Current clinical diagnosis of schizophrenia, schizoaffective disorder, other psychosis, bipolar disorder or current major depression by DSM-5 criteria. Prior history of major depression will not be exclusionary. (Physician Evaluation)
2. Active suicidal intent or plan based on clinical assessment. (SRMP Assessment by Study Physician)
3. Current or recent (past 6 months) alcohol or substance use disorder (DSM-5 criteria). (Physician Evaluation)
4. Current diagnosis of other major neurological disorders, including Parkinson's disease, multiple sclerosis,CNS infection, Huntington's disease, and amyotrophic lateral sclerosis. (Physician Evaluation)
5. Clinical stroke with residual clinical deficits. MRI findings of cerebrovascular disease (small infarcts, lacunes, periventricular disease) in the absence of clinical stroke with residual neurological deficits will not lead to exclusion. (Physician Evaluation)
6. Acute, severe, unstable medical illness. For cancer, patients with active illness or metastases in the last 12 months will be excluded, but past history of successfully treated 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) \< 44 ml/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. (Laboratory Report)
11. Use of benzodiazepines in lorazepam equivalent doses equal to or greater than 2 mg daily. (Patient Report)
12. For MRI, metal implants and pacemaker, and claustrophobia such that the patient refuses MRI. (Patient Report)
13. Radiation exposure in the prior 12 months that, together with 18F- Florbetapir will be above the FDA annual radiation exposure threshold. (Patient Report and Physician Evaluation)
14. Severe vision or hearing impairment that would prevent the participant from performing the psychometric tests accurately. This will be a clinical determination by the study physician without formal testing or audiometry.(Physician Evaluation)