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 to and during the study.
• Willingness to undertake multiple MRI scans
• Meet the National Institute of Aging - Alzheimer's Association core clinical criteria 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 onset and slow progression over the last one year before screening MUST be corroborated by an informant.
• Participants on acetylcholinesterase inhibitor or memantine therapy for AD must be on a stable dose for at least 12 weeks prior to baseline visit.
• Participants must have an identified caregiver/study partner that can accompany participant 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 months of 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 II diabetes mellitus (HbA1c \> 7%), kidney failure, liver failure, hepatitis, blood disorders, clinical symptomatic orthostatic hypotension, and unstable or significantly symptomatic cardiovascular disease
• Significant disease of the Central Nervous System (CNS) such as brain tumor, seizure disorder, subdural hematoma, cranial arteritis, or clinically significant stroke
• Major depression, schizophrenia, or other major psychiatric disorder defined by DSM-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, narcotic analgesics, nicotine (tobacco, patches, gum, lozenges, etc.), Cannabis sativa (herb or edibles), beta blockers and anti-depressant medications that have not been at stable dosage for two months (including SSRIs, SNRIs)
• Non-Alzheimer dementia such as vascular dementia, normal pressure hydrocephalus, or Parkinson'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 the study
• Contraindications to Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopic Imaging (MRSI) scans (some metal implants, pacemakers, claustrophobia)