Indications play an important role in how pharmacists recommend brain health products.
Clinical trials of new investigational drugs in Alzheimer’s disease have raised safety concerns, making it more important for healthcare providers to set appropriate expectations for investigational drugs and OTC supplements for brain health. .
Lecanemab
An experimental therapeutic called lecanemab is the latest development in the drug discovery process for Alzheimer’s disease. Lecanemab generated a lot of buzz and excitement in the Alzheimer’s disease community as the trial met its primary endpoint and all secondary endpoints.1
The primary endpoint was the change from baseline in the score on the Clinical Dementia Assessment-Box Total Rating Scale at 18 months.1 Secondary endpoints were scores on the 14-item cognitive subscales of the Alzheimer’s Disease Assessment Scale (ADAS-cog14), the Alzheimer’s Disease Composite Score (ADCOMS), and the Alzheimer’s Disease Collaborative Study – Activities of Daily Living Score in Mild Dementia . disorders (ADCS-MCI-ADL) and, most importantly, changes in PET amyloid load.1
A secondary endpoint, change in amyloid burden on PET, was a key finding of this study. Amyloid beta is a prominent feature found in the brains of Alzheimer’s patients and may initiate or enhance the disease.1
At the same time, the reduction of brain amyloid burden caused significant toxicity.1 One of the significant toxicities of lecanemab was amyloid-associated imaging abnormalities (ARIA).1
These are brain imaging abnormalities that appear on MRI and are associated with the use of monoclonal antibodies that target amyloid beta.2 These imaging abnormalities may manifest as cerebral edema (ARIA-E) or cerebral hemorrhage (ARIA-H).2 Both ARIA-E and ARIA-H were receiving lecanemab treatment.1 These adverse events are suspected to have caused three post-study deaths to date.3
Neuriba
Neuriva is a popular OTC supplement recommended by pharmacists to support brain health. Neuriva Original contains 100mg of coffee fruit extract (coffee arabica) and 100 mg phosphatidylserine.Four
Neuriva Plus contains 200 mg of coffee fruit extract (coffee arabica), 100 mg phosphatidylserine, 1.7 mg vitamin B6 (as pyridoxine hydrochloride), 680 mcg dietary folate equivalent (400 mcg folic acid), and 2.4 mcg vitamin B12 (as cyanocobalamin).Five Neuriva may increase brain-derived neurotrophic factor (BDNF) levels, enhance neuronal membrane function, and restore diminished acetylcholine neurotransmitter activity.7
There is some evidence to support the two main ingredients of Neuriva, coffee fruit extract and phosphatidylserine. In a trial involving adults with mild cognitive decline, giving coffee fruit extract improved reaction time in a post hoc analysis of the study.6
In another trial in adults with mild cognitive decline, phosphatidylserine may have resulted in improvements in delayed verbal recall in the study’s post hoc analysis.8 Both of these findings occurred in the post hoc analysis of each study and are therefore only study observations outside of the prespecified primary outcome.
In each study, there were no statistically detectable differences in the prespecified primary outcome that the authors planned to find at the start of the study. The evidence is therefore limited.
Prevegen
Prevagen is another product commonly recommended by pharmacists to support brain health. Prevagen consists of vitamin D (50 mcg as D3 cholecalciferol) and apoaequorin 10 mg (regular strength).920mgTenor 40 mg.11 Prevagen works primarily through its active ingredient apoaequorin.
Apoaequorin is a calcium-binding protein found in luminous jellyfish (aequorea victoria).12 Calcium-binding proteins play a role in regulating intracellular calcium homeostasis, which is part of neuronal function.
Decreased intracellular calcium-binding proteins and their dysregulated distribution in the central nervous system may contribute to age-related cognitive decline, neuronal damage, and death.13 The Madison Memory study was a randomized, double-blind, placebo-controlled study investigating the effects of Prevagen on cognitive performance in adults with self-reported cognitive impairment.14
Results showed that people without cognitive impairment and those with very mild cognitive impairment showed statistically significant improvements in cognitive function compared to the placebo treatment group.14 However, the use of Prevagen in patients with mild to severe cognitive impairment remains inconclusive.14
One of the exclusion criteria for this trial was a history of significant neurological disease, dementia, or associated memory impairment, so the benefit of Prevagen in this patient population remains unclear.14 Additionally, the study tested people who reported some cognitive impairment, but did not find it to show a statistically significant improvement in cognitive function compared to the placebo treatment group.
The benefits of Prevagen for those with self-reported mild to moderate cognitive impairment remain unclear.14 There is also strong evidence to suggest that Prevagen is not digested in the intestine, and there is also evidence to suggest that Prevagen does not cross the blood-brain barrier.15,16
Which product does the pharmacist recommend?
Much of the difference in recommendations between Neriva and Prevagen is due to patient preference based on prescription. Neuriva comes in capsules, gummies, and energy shots. Prevagen is available in capsule, chewable and protein shake formulations.
Note that indications play an important role in which products can be recommended to which groups of individuals. Prevagen is only for use in adults with no history of cognitive impairment. Nuliba can be used by people with and without cognitive impairment.
Pharmacists should also be aware that they recommend appropriate non-pharmacological recommendations to support individuals with cognitive impairment, including establishing predictable routines and maintaining a consistent environment. This includes keeping requests and requirements simple and avoiding complex tasks. In general, it helps to change the patient’s environment so that it is easier for them to understand. A large clock, calendar, or door sign can help.
Finally, we should not confront denial in Alzheimer’s patients. Even in individuals without cognitive impairment, pharmacists can recommend interventions to support an individual’s cognitive health, i.e. regular physical and social activity.19,20
References
1. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer’s disease. New England Journal of MedicineNovember 2022: 1-13. doi:10.1056/nejmoa2212948
2. Salloway S, Chalkias S, Barkhof F, et al. Amyloid-related imaging abnormalities in two phase 3 trials evaluating aducanumab in patients with early Alzheimer’s disease. Department of Neurology, JAMA2021;79(1):13-21. doi:10.1001/jamaneurol.2021.4161
3. Pilar C. Scientists have linked deaths in third clinical trial to experimental Alzheimer’s drug. Chemistry. https://www.science.org/content/article/scientists-tie-third-clinical-trial-death-experimental-alzheimer-s-drug. Published December 21, 2022. Accessed December 29, 2022.
4. Neuriva original brain health supplement with coffee cherry extract and phosphatidylserine. Schiff vitamin. https://www.schiffvitamins.com/collections/capsules/products/neuriva-original-brain-performance-clinically-proven-brain-supporting-supplement-with-natural-ingredients. Accessed 28 December 2022.
5. Neuriva Plus, a brain health supplement with coffee cherry extract and phosphatidylserine. Schiff vitamin. https://www.schiffvitamins.com/collections/capsules/products/neuriva-plus-brain-performance-clinically-proven-brain-supporting-supplement-with-natural-ingredients.
6. Robinson JL, Hunter JM, Reyes Izquierdo T, et al. Short- and long-term cognitive effects of coffee cherry extract in older adults with mild cognitive decline. Aging, Neuropsychology, and Cognition2020;27(6):918-934. Doi:10.1080/13825585.2019.1702622
7. Jorissen BL, Brons F, Van Boxtel MP, Riedel WJ. Safety of soy-derived phosphatidylserine in the elderly. nouta neuroscience2002;5(5):337-343. Doi: 10.1080/1028415021000033802
8. Kato-Kataoka A, Sakai M, Ebina R, Nonaka C, Asano T, Miyamori T. Soybean-derived phosphatidylserine improves memory function in elderly Japanese subjects with memory impairment. J Clin Biochem Nutr2010;47(3):246-255. doi:10.3164/jcbn.10-62
9. Prevagen Regular Strength Capsules 10mg, 30 counts. Prevagen. https://prevagen.com/products/prevagen-regular-strength-brain-health-memory-supplements. Accessed 28 December 2022.
10. Prevagen Extra Strength Capsules 20mg, 30 counts. Prevagen. https://prevagen.com/products/prevagen-extra-strength-brain-health-memory-improvement-supplements. Accessed 28 December 2022.
11. Prevagen Professional Formula Capsules 40mg, 30 Count. Prevagen. https://prevagen.com/products/prevagen-professional-healthy-brain-function-supplements. Accessed 28 December 2022.
12. Apoaequorin. Alzheimer’s Disease Drug Discovery Foundation. https://www.alzdiscovery.org/cognitive-vitality/ratings/apoaequorin. Published June 13, 2016. Accessed December 28, 2022.
13. Brini M, Calì T, Ottolini D, Carafoli E. Neuronal calcium signaling: function and dysfunction. Cellular and Molecular Life Science2014;71(15):2787-2814. doi:10.1007/s00018-013-1550-7
14. Moran DL, Underwood MY, Gabriel TA, Lerner KC. Effects of apoaequorin-containing supplements on language learning among community older adults. Adv Mind Body Med2016;30(1):4-11.
15. Moran DL, Tete AO, Goodman RE, Underwood MY. Safety evaluation of the E. coli-expressed calcium-binding protein apoaequorin. Regular Toxicol Pharmacol2014;69(2):243-249. doi:10.1016/j.yrtph.2014.04.004
16. Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD, eds. Fundamental Neurochemistry: Molecular, Cellular, and Medical AspectsPhiladelphia, Pennsylvania: Lippincott Raven. 1999.
17. Galvin JE, Roe CM, Powlishta KK, et al. AD8: Brief informant interview for detecting dementia. neurology2005;65(4):559-564. doi:10.1212/01.wnl.0000172958.95282.2a
18. Spencer B, White L. Coping with Behavioral Changes in Dementia: A Guide for Family CaregiversAnn Arbor, Michigan: Whisppub LLC; 2015.
19. Buchman AS, Yu L, Wilson RS, et al. Physical activity, common brain pathologies, and cognition in community-dwelling older adults. neurology2019;92(8):e811-e822. doi:10.1212/WNL.0000000000006954
20. Cacioppo S, Grippo AJ, London S, Goossens L, Cacioppo JT. Loneliness: Clinical Importance and Interventions. perspective psychology2015;10(2):238-249. Doi: 10.1177/1745691615570616
