Curcumin and Cognition: What's the Link?

The accumulation of abnormal proteins in brain cells is thought to be at the root of brain damage in cognitive loss, a devastating disorder to both the people it affects and society as a whole. 

At the root of the damage that causes this increasingly pervasive form of cognitive loss is a sticky compound called beta-amyloid that disrupts communications between brain cells. To protect against damage caused by these abnormal proteins, our bodies activate an immune response. However, this leads to excessive inflammation that further damages the brain and contributes to cognitive dysfunction.

Other aging-related biologic pathways also contribute to cognitive decline. One of the hallmarks of aging is DNA damage, which causes cellular malfunction and eventual cell death. As this damage spreads, people’s cognitive function can become affected. This is apparent during the final stages of cognitive loss, when so much of the brain is compromised that normal brain function is no longer possible. 

To move past the state of stagnation where research into a cure currently resides, the National Institutes of Health (NIH) called for a summit of experts to focus on understanding how cognitive loss damages the brain, in the hopes of developing new preventive strategies as well as viable treatment options (1). This perspective has led scientists to look into the distribution, patterns, and determinants of cognitive loss incidence, and uncover some promising leads.

The Indian Spice Curcumin Has Brain-Preserving Properties

Although frequent among the rest of the world population, the incidence of cognitive loss disorders is remarkably lower in India. One possible explanation for this is the unique diet of the local population. One common ingredient used extensively in Indian cuisine is curcumin, an herb-based substance found in turmeric and other spices. Research done on curcumin has shown that it displays several anti-aging properties through multiple molecular mechanisms at the cellular level (2, 3).

Curcumin has long been of interest to researchers due to preliminary studies that show that it has brain-protecting properties and may preserve cognitive function (4, 5). Initially, these promising properties made curcumin a prime target to develop medication for memory preservation. However, the intrinsic pathways that allow curcumin to exert its effects were not well understood. Also, curcumin’s poor bioavailability — the amount of available drug in the body’s circulation — has frustrated researchers trying to develop a more efficient drug. 

Nevertheless, recent developments have allowed researchers to find practical ways to administer curcumin to humans in clinical trial settings. A recent study from UCLA showed that curcumin helped preserve memory and diminished amyloid content in the brain of participants. This 18-month, placebo-controlled clinical trial is the first proof-of-concept study for the development of a cognitive loss disorder drug based on curcumin (6).

Can Scientists Develop a Drug Based on Curcumin?

Building on the success of this initial trial in humans, a group of Taiwanese researchers have recently tested a structurally-modified version of curcumin called TML-6 (7). The structural modification is designed to improve curcumin’s stability and bioavailability.

TML-6 was tested extensively in cell cultures and an animal model. The researchers used human cells to show that TML-6 interacted with its intended targets and that the interaction between the compound and the cells was safe. 

To test its effects in live animals, the researchers studied TML-6 in mice that had a genetic predisposition for a cognitive loss disorder. These mice received a small dose of TML-6 with their regular diets. The researchers observed that the mice’s cognitive abilities were preserved after receiving the curcumin analog. They also saw that the levels of inflammation and beta-amyloid were significantly lower in these mice. 

The study’s results confirm curcumin as a good candidate for the development of a cognitive loss disorder drug. More research will be needed to further understand the way curcumin interacts with brain tissues. In the coming years, we will likely see more lab studies and even human clinical trials evaluating the effects of curcumin and mimicking compounds like TML-6 on cognitive loss. 

References:

1. NIH Summit Delivers Recommendations to Accelerate Therapy Development. Available online: https://www.nih.gov/news-events/news-releases/
2. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin. Int J Biochem Cell Biol. 2009;41(1):40-59.
3. Alappat L, Awad AB. Curcumin: evidence and mechanisms. Nutr Rev. 2010;68(12):729-738. doi:10.1111/j.1753-4887.2010.00341.x
4. Goozee KG, Shah TM, Sohrabi HR, et al. Examining the potential clinical value of curcumin. Br J Nutr. 2016;115(3):449-465. doi:10.1017/S0007114515004687
5. Mishra S, Palanivelu K. Ann Indian Acad Neurol. 2008;11(1):13-19. doi:10.4103/0972-2327.40220
6. Small GW, Siddarth P, Li Z, et al. Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin: A Double-Blind, Placebo-Controlled 18-Month Trial. Am J Geriatr Psychiatry. 2018;26(3):266-277. doi:10.1016/j.jagp.2017.10.010
7. Su IJ, Chang HY, Wang HC, Tsai KJ. A Curcumin Analog Exhibits Multiple Biologic Effects in a Mouse Model. Int J Mol Sci. 2020;21(15):5459. Published 2020 Jul 30. doi:10.3390/ijms21155459