Safety and Target Engagement of Centella Asiatica in Cognitive Impairment

Inclusion criteria:

• Age 60-85, male and female

• Sufficient English language skills to complete all tests

• Sufficient vision and hearing to complete all tests

• No known allergies to Centella asiatica

• Absence of significant depression symptoms (Geriatric Depression Scale-15 score of < 5).

• Total score of <2 on the suicidal ideation subscale (measures 3, 7, 11, 12 and 14)of the Geriatric Depression Scale.

• Body Mass Index (BMI) greater than 17 and less than 35 at screening

• General health status that will not interfere with the ability to complete the study

• Willingness to discontinue all botanical dietary supplements for one week prior toand during the study.

• Willingness to undertake multiple MRI scans

• Meet the National Institute of Aging - Alzheimer's Association core clinicalcriteria for MCI or probable AD dementia with a Clinical Dementia Rating score of 0.5-1 and Mini Mental State Examination score of 20-28 at screening and baseline

• Participants who report a history of participative memory decline with gradual onsetand slow progression over the last one year before screening MUST be corroborated byan informant.

• Participants on acetylcholinesterase inhibitor or memantine therapy for AD must beon a stable dose for at least 12 weeks prior to baseline visit.

• Participants must have an identified caregiver/study partner that can accompanyparticipant to all study visits.

Exclusion criteria:

• Current smoking, alcohol, or substance abuse according to DSM-V criteria

• Women who are pregnant, planning to become pregnant, or breastfeeding

• Men who are actively trying to conceive a child or planning to within three monthsof study completion

• Severe aversion to venipuncture

• Abnormal labs indicating asymptomatic and untreated urinary tract infection

• Cancer within the last five years, with the exception of localized prostate cancer (Gleason Grade < 3) and non-metastatic skin cancers

• Comorbid conditions such as type I diabetes mellitus, poorly controlled type IIdiabetes mellitus (HbA1c > 7%), kidney failure, liver failure, hepatitis, blooddisorders, clinical symptomatic orthostatic hypotension, and unstable orsignificantly symptomatic cardiovascular disease

• Significant disease of the Central Nervous System (CNS) such as brain tumor, seizuredisorder, subdural hematoma, cranial arteritis, or clinically significant stroke

• Major depression, schizophrenia, or other major psychiatric disorder defined byDSM-V criteria

• Medications: anti-epileptics, sedatives, amitriptyline, anticoagulants (e.g.,warfarin), investigational drugs used within five half-lives of baseline visit,systemic corticosteroids, neuroleptics, anti-Parkinsonian agents, narcoticanalgesics, nicotine (tobacco, patches, gum, lozenges, etc.), Cannabis sativa (herbor edibles), beta blockers and anti-depressant medications that have not been atstable dosage for two months (including SSRIs, SNRIs)

• Non-Alzheimer dementia such as vascular dementia, normal pressure hydrocephalus, orParkinson's disease

• MMSE score of < 20 or > 28

• Unwilling to maintain stable dosage of AD medications throughout study duration

• Unwilling to maintain stable dosage of intervention throughout the course of thestudy

• Contraindications to Magnetic Resonance Imaging (MRI) and Magnetic ResonanceSpectroscopic Imaging (MRSI) scans (some metal implants, pacemakers, claustrophobia)