A Comparative Analysis of Prevagen® Supplementation and Current Nootropic Agents Collin Belk, Kelly Ferris, Kirsten Carstarphen, Jace Engstler, Dr. David Roman Background: Manufactured & Marketed by Quincy Bioscience starting in 2007 Claims to improve memory and support healthy brain function, sharper mind, and clearer thinking Available as oral capsules & chewables Regular (10 mg) & Extra-Strength (20 mg) options In 2017, the FTC and N.Y. Attorney General files lawsuits against Quincy Bioscience for promoting false claims for Prevagen Quincy's annual revenue has grown 234% from 2009 to 2012 -- from $5.3 million to $17.8 million Prevagen: Active Ingredient and MOA Apoaequorin, a calcium-binding protein found in jellyfish Proposed MOA: Limit age-related calcium-mediated toxicity of neurons through regulation of intracellular calcium homeostasis Prevagen: Biological Plausibility Pharmacokinetic limitations Digestion Bioavailability Blood-Brain Barrier ISL - AD8 0-2 Apoaequorin 10.86% t56=4.40 p<.001 Control 3.79% t32=1.059 p=.298 ISL-DR – AD8 0-2 15.82% t56=3.010 p=.004 7.41% t32=1.202 p=.238 ISL-DR – AD8 2-5 13.74% t42=4.913 8.14% t36=1.423 p=.163 Modafinil FDA-approved for treatment of narcolepsy, obstructive sleep apnea and shift work sleep disorder Drug Class: Central Nervous System Stimulant MOA: Exact mechanism unknown. Binds to dopamine transporter, thereby inhibiting dopamine uptake Nootropic Properties: Molecular weight: 273 kDa LogP: 0.6 Consistently shown to enhance executive functions, including decision making, planning and fluid intelligence Inconsistent results observed for short-term memory and learning tasks Madison Memory Study Study Design Randomized, double-blind, placebo controlled Population N: 218, aged 40-91 years old Cognitive function: AD8 screening test Normal: 0-2 Impaired: 2-5 Intervention 90 days 1 oral capsule of 10 mg apoaequorin daily Computerized testing sessions at baseline, day 8, day 30, day 60 and day 90 International Shopping List (ISL) International Shopping List - Delayed Recall (ISL-DR) Comparison 1 size and color matched placebo capsule daily Same computerized testing sessions Outcome Change in performance on tasks from baseline to day 90 on: ISL ISL-DR Madison Memory Study: Limitations Subjective bias and conflicts of interest Did not directly compare apoaequorin to placebo to show it worked better Paired t test degrees of freedom different than what would be expected Did not provide evidence or rationale for apoaequorin’s mechanism in reaching therapeutic target Donepezil FDA approved in 1996 for treatment of mild, moderate & severe Alzheimer’s Disease MOA: Acetylcholinesterase inhibitor Nootropic Properties: Good bioavailability & BBB Penetration Small molecule (415.96 kDa) LogP 3.6 Shown to have mild improvements assessed cognitive function in Alzheimer’s patients Inconsistent results in several studies on healthy adults Amphetamine Salts/ Methylphenidate: FDA approved in 1996 for the treatment of ADHD Known as “smart pills” and are believed by many to enhance cognitive ability MOA: Blocks reuptake of norepinephrine and dopamine and increases their release into extraneuronal space Results of over 40 laboratory studies consisting of healthy non-elderly adults assessed three types of cognition and concluded the following: Learning: some enhancement Working Memory: Some enhancement for lower performers Cognitive Control: some benefit but limited support for general population Future Directions: Study Objectives: Evaluate claims made about Prevagen by Quincy Bioscience, and determine if these claims are scientifically supported Compare FDA approved drug targets for nootropic agents and their biologic plausibility compared to Prevagen Exploration of other natural products used to enhance memory/cognition What are the current recommendations in the community? How do pharmacists in this practice setting handle this question? Community pharmacists’ input on Prevagen Methods: Literature review utilizing PubMed A comparison of nootropic agents, mechanisms of action, pharmacological basis and how it relates to Prevagen’s proposed mechanism and biochemical properties Effects of commonly used cognitive enhancers such as caffeine and drugs of abuse. What pharmacies endorse the sale of Prevagen or other “memory enhancing” supplements