Attacking Alzheimer’s with Ashwagandha: An Alternative Antidote Against Amyloid-B

• Background & Introduction: 
  • Alzheimer’s is a neurodegenerative disorder that causes issues with memory, cognition, and behavior. Falling under the umbrella term of dementia, Alzheimer’s is a disease that afflicts a large population, however, has no cure nor formal treatment. Alzheimer’s defining feature in the brain is the presence of Amyloid-B peptide plaque and Tau protein filament tangles that both work together to continue a feedback loop that causes the degeneration of nerves in the brain and the communication networks between neurons, eventually leading to their death.
  • Ashwagandha is a traditional Indian herb that is used in Ayurvedic medicine, or traditional Indian healthcare/healing methods. The medicinal form is derived from the shrub’s roots and fruit and is dried and consumed usually in capsule form. Specifically for Alzheimer’s, chemical compounds called withanolides found in multiple forms in ashwagandha are thought to help with the Amyloid-B peptide plaque formation.
• The Pseudoscience Behind It
  • Ashwagandha has been thought to be a “magical treatment/supplement” with a long list of benefits largely based off of the traditional Indian uses for it. It’s been mostly toted as having “adaptogenic” qualities or assisting in adapting the body and mind to natural and normal stressors, helping in mood and physical health. With such a list of diseases such as asthma, cancer, and anemia that it has been told to help fight, the actual herb has had little scientific research done on it and the side effects, both short and long-term, are unknown. The term adaptogen and lack of scientific basis behind its healing and disease-fighting properties lead ashwagandha into the pseudoscience territory where users and proponents for homeopathic “cure-alls” and “preventatives” reign.
    
• A Possible Alzheimer’s Cure
  • Ashwagandha has thought to be a possible Alzheimer’s cure considering the properties that the withanolides carry have the ability to bind to active fibril forming locations and prevent the formation of the B-Amyloid plaque that is a large part of Alzheimer’s development. This would function as a preventative measure, however, the methanol compounds that were extracted from ashwagandha were also seen to have stimulated neurite outgrowth, or when developing nerves create new projections as induced by nerve growth factors. This function serves to help heal any neurodegeneration that has already occurred in the brain, providing a stimulant for the regeneration of the neural networks that are affected by Alzheimer’s. Working both as a preventive measure and a regenerative treatment, ashwagandha appears to be a possible cure for Alzheimer’s.

Clinical Trial Methodology

• Treatment groups:
  • Participants: Randomly selected amongst populations of interested patients affected by early-stage Alzheimer’s from clinics, local Primary Care/Geriatric/Neurologists’ offices, and nursing homes compensated with a standard monetary sum.
    • Considering these are geriatric patients and ones affected by dementia, need informed consent signed by the participant and designated healthcare proxy if dementia progresses during the experiment and participant can’t convey his/her health needs/desires down the line.
    • Informed consent needs to include: the ability to leave at any point during the experiment, awareness of unknown side effects, awareness of placebo in the experiment, understand obligation to fulfill and physical and mental risks (PET scan, CANTAB, MMSE) involved for tests at every point of the experiment (beginning, middle, end), understanding that their consent now is for the entire duration of experiment, even if they forget about the consent form down the line (as witnessed by healthcare proxy).
  • Sample Size: For a significant difference (p<.05 & 90% power) in the results need a minimum sample size of 80 patients in final results. Starting size of 200 participants would be ideal, as many will not continue with the study due to other circumstances or conflicts during the testing period.
  • Control: Subjects take a placebo capsule without ashwagandha orally, daily.
  • Experimental: Subjects take capsule with ashwagandha powder orally, daily.
• Experimental Parameters and Testing:
  • Memory – Memory Test ( CANTAB Mobile)- subjects will take an online memory test on a computer to quantify memory data collected and progress over time
  • Cognition- Cognitive Test (MMSE) – subjects will take a cognitive test to test for thinking and problem solving over the course of the treatment
  • Plaque Buildup- PET scan for amyloid plaque in the brain before, once in the middle, and after the course of treatment
• Experiment Plan:
  • Participants take their designated capsule, daily, over the course of 6 months. A PET scan specifically for amyloid plaque will be conducted prior start as well as a CANTAB test and MMSE test to function as a baseline. At midpoint (3 months), the second set of tests will be done to determine if any significant change had occurred in all three parameters. A general health check will be done to account for the drug’s effect on other parts/functions of the body. At the end of the treatment course (6 months), the same tests and check-up will be done to all participants still remaining in the study.
• Considerations for risk towards participants
  • Risks mainly are focused on side-effects of this herb on the participants in this study. Considering the short and long-term risks for this herb are unknown and undocumented. Cytotoxic properties are unknown and a basic health check should be done in addition to results to see if the drug has affected any other parts and functions of the body.
    • Must be ready to halt experiment if long-term effects demonstrate fatal or deadly side-effects in a large percentage of participants.
  • Considerations also include the patients progressing quickly in their Alzheimer’s, especially in the control group/ They must be monitored since Alzheimer’s and severe dementia can lead to reckless and dangerous behaviors as well as inability to eat/feed the participant, causing possible death.
  • Since patients will most likely be older in age, must account for natural death due to other factors and calculate the statistics between the experimental and control to ensure death is not related to the consumption of the drug.
  • An additional consideration is that if Alzheimer’s progresses quickly and the patient can no longer consume/take in the drug on their own accord, that the experiment cannot continue in that participant and will instead be logged as data stating that the pill can longer be administered due to severe dementia.
• Potential Results & Quantifiable Success 
  • Potential results include a positive trend in cognitive ability in the experimental group contrasted against a negative trend in the control displaying how the drug helps treat and possibly reverse the symptoms of Alzheimer’s. Additional results can include no trend in experimental group meaning the drug has prevented progression, however, has not contributed to the formation of new neural networks/healing. A final option was that the experimental and the control group had shown little to no difference in mean and SD leading to the conclusion that there was no discernable significant effect on the populations by the drug on the progression of Alzheimer’s.
  • Quantifiable Success would be a positive or zero trends for the experimental group and a negative trend for the control since it would signal an effect by the drug compared to the placebo. If the final sample size was greater than or equal to 80 then the data collected would be statistically significant by sample size and if the given results were calculated to be significant using a two-way repeated measures Analysis of Variance the drug would demonstrate a definite effect.