Validated, unified theory of Alzheimer Disease illuminates two essential research questions
Alison Ruth Kennedy- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
A 2001 unified theory of thiamine deficiency (TD) in Alzheimer Disease (AD) (1‐p.85) was validated in 2015 (2), and published in 2017 (3). Update?
Method
Scientific literature review on topic of thiamine and/or AD. PUBMED, elibrary.wiley.com, mspace.lib.umanitoba.ca
Result
1. Thiamine supplementation can potentially correct key AD abnormalities: the cholinergic deficit (1‐p.64, 4), B‐Amyloid (1‐p. 77, 3), tau (5), neuroinflammation (4, 5,6, 7) and memory (1‐p59).
2. Limited oral thiamine supplementation trials in AD have had mixed results (1‐p49, 6).
Conclusion
Essential research questions:
a. What causes TD in AD? (altered thiamine requirements, excretion, absorption, transport, metabolism, or diet and other factors*?) (1)
b. What is the optimal treatment of TD in AD? (control for medications*, medical conditions* and dietary components affecting thiamine intake and utilization* (1‐p. 52, 1‐p.53,9). Consider advantages of intramuscular injections vs. oral treatments (8), need for other nutrients (1‐p.52), proven thiamine treatments in TD diseases.
References:
1. Kennedy, A.R. (2001). The potential role of thiamine in the pathogenesis and treatment of Alzheimer’s Disease. M.Sc. dissertation. University of Manitoba, Winnipeg.
2. Pan, X. (2015). Measurement of brain thiamine metabolites for Alzheimer Disease diagnosis. 2015 Nov 26. doi: 1016/j.ebiom.2015.11.039
3. Kennedy, A.R. (2017). Scientific evidence supporting a unified theory of Alzheimer Disease. Alzheimers Dement,13(7S)_ Part_31/p.P1478‐P1478
4. Lu’o’ng, K., Nguyen, LT (2011). Role of thiamine in Alzheimer’s Disease. Am J Alzheimer’s Dis Other Demen., 26(8):588‐598.
5. Tapias, V. et al. (2018). Benfotiamine treatment activates the Nrf2/ARE pathway and is neuroprotective in a transgenic mouse model of taupathy. Hum Mol Genet Aug 15; 27(16): 2874‐2892.
6. Fessell, J. (2021). Supplemental thiamine as a practical, potential way to prevent Alzheimer’s disease from commencing. Alzheimers Dement: Translational Research and Clinical Interventions. 7 (1)/e12199.
7. Sambon, M. et al. (2021). Neuroprotective effects of thiamine and precursors with higher bioavailability: Focus on benfotiamine and dibenzoylthiamine. Int. J. Mol. Sci. 22(11):5418.
8. Baker, H., et al. (1980). Oral versus intramuscular vitamin supplementation for hypovitaminosis in the elderly. J Am Geriatr Soc., 28(1):42‐45.
9. Vora, B. et al. (2020). Drug‐nutrient interactions; discovering prescription drug inhibitors of the thiamine transporter ThTF‐2 (SLC19A3). Am J Clin Nutr., 111(1), 110‐121.