safety and target engagement of centella asiatica in cognitive impairment

Conditions: Mild Cognitive Impairment; Alzheimer's Disease

Summary: this clinical trial is focused on determining whether biological signatures of target engagement by a centella asiatica water extract product administered orally for 6 weeks can be measured in comparison to placebo. this study will also assess the safety and tolerability of the centella asiatica water extract product.

this phase i study is a randomized, double-blind, placebo-controlled, clinical trial of 48 participants to evaluate safety, tolerability, and biological signatures of target engagement of brain neuronal viability, oxidative stress, and brain mitochondrial activity of a centella asiatica water extract product (cap) in older adults aged 60-85 years with mild cognitive impairment or mild alzheimer's disease (ad). the intervention is taken orally daily for six weeks and pre and post assessments will be collected.

Eligibility criteria:
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 \ 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)