The mental processes that enable us to think, process and understand information (such as memory, language and problem-solving) are what define cognitive function. Cognitive decline is an impairment of thinking and memory loss, typically associated with the ageing brain.

Preventing and managing cognitive decline requires a multilayered clinical approach, founded on the following and adopted as appropriate for the individual:¹

• Supporting the tissue with neuroprotection
• Boosting cognitive function
• Eliminating persistent pathogens (as appropriate)
• Reducing chronic neuroinflammation
• Supporting microvascular and endothelial health
• Boosting neurotropic factors in the brain
• Boosting mitochondrial function, and
• Reducing insulin resistance and cardiovascular risk (as appropriate)

The Nrf2 Pathway

Priming the Nrf2 pathway is one way to address multiple aspects of neurocognitive decline, and recognised as one of the core Functional Herbal Therapy strategies recommended by Professor Kerry Bone. The Nrf2 pathway supports and enhances cellular health and protection (cytoprotection).²

The Keap1/Nrf2/ARE pathway describes a targeted approach to antioxidant protection, responsive to oxidative and chemical stress. In short, chemical stress disrupts the tethering of Keap1 and Nrf2. Once free, Nrf2 (a transcription factor) can then be activated and moved (translocated) to the nucleus where it binds to ARE. This induces the synthesis of a series of antioxidant, detoxifying, protective, and anti-inflammatory enzymes (see Figure 1). Activation of this pathway can also be achieved through phytotherapy, which can subsequently minimise damage caused by constant exposure to both external and internal factors.²

In addition, Nrf2 is important for maintaining mitochondrial homeostasis, which is of even greater importance in conditions featuring oxidative and inflammatory stress.² * To review the Nrf2 pathway in further depth refer to Functional Herbal Therapy: A Modern Paradigm for Clinicians by Kerry Bone.

Figure 1. The Keap1/Nrf2/ARE Pathway³

ARE, antioxidant response element; Cul3, cullin 3; GPx, glutathione peroxidase; GSH, glutathione; GST, glutathione S-transferases; HO-1, heme oxygenase-1; Keap1, Kelch-like ECH associated protein 1; Maf, musculoaponeurotic fibrosarcoma; NQO1, NADPH quinone oxidoreductase 1; Nrf2, nuclear factor erythroid 2-related 2; P, phosphorylated; SOD, superoxide dismutase; Ub, ubiquitination

Curcumin and Cognitive Function

Bioavailable curcumin, derived from Turmeric, is one such phytochemical that not only acts on the Nrf2 pathway but simultaneously lessens neuroinflammation, boosts brain-derived neurotrophic factor (BDNF) and enhances cognition.^1,4 This makes curcumin one of the most important phytochemicals to feature in holistic treatment strategies aimed at preventing cognitive decline. Using herbs and nutrients that support multiple clinical outcomes and act via multiple relevant targets in the body best supports the patient, as is the case for bioavailable curcumin.¹

A recent systematic review of 12 studies (11 clinical trials and 1 cohort study), in adults with and without neurocognitive disorders, found that curcumin:⁵

• Significantly improved working memory and mood in healthy older adults with no prior cognitive or psychosocial impairments, with a 20% improvement in cognitive performance, suggesting possible benefits in preventing cognitive decline
• Significantly improved cognitive performance and biomarkers with improved mini-mental state exam (MMSE) scores by 15% in adults with pre-existing cognitive impairment and dementia, highlighting its neuroprotective potential
• Significantly improved cognitive performance and cerebrovascular reactivity, as reflected by changes in blood flow to the brain, in adults with obesity and prediabetes, indicative of metabolic and cognitive benefit
• Significantly enhanced cognitive performance in adults with major depressive disorder (MDD), suggesting suitability for use as an adjuvant treatment for depression
• Significantly improved cognitive function in adults with chemotherapy-induced cognitive impairment, and
• In 11 of the 12 included studies, significantly improved cognitive performance and serum biomarkers among groups that consumed curcumin, compared to placebo or alternate interventions

This evidence supports the use of curcumin as a standout inclusion in the treatment regimen of adults at risk of, or already experiencing cognitive decline or neurocognitive disorders.⁵

* To learn more about bioavailable curcumin and other essential herbs and strategies for the prevention of dementia, listen to The MediHerb Podcast – Kerry Bone – Cognitive Care: Holistic Strategies for Dementia and Alzheimer's Prevention series.

References

1. The MediHerb Podcast. Kerry Bone - cognitive care: holistic strategies for dementia and Alzheimer's prevention (part 2) [podcast]. Eight Mile Plains (AU): Integria Healthcare; 2024 [cited 2024 Sep 19]. Available from: https://themediherbpodcast.podbean.com/e/cognitive-care-holistic-strategies-for-dementia-and-alzheimers-prevention-part-2/

2. Bone K. Functional herbal therapy: a modern paradigm for clinicians. London: Aeon Books; 2021.

3. Ahsan H, Islam SU, Ahmed MB, Lee YS. Role of Nrf2, STAT3, and Src as molecular targets for cancer chemoprevention. Pharmaceutics. 2022 Aug;14(9):1775. DOI: 10.3390/pharmaceutics14091775

4. Nunes YC, Mendes NM, Pereira De Lima E, Chehadi AC, Lamas CB, Haber JFS, et al. Curcumin: a golden approach to healthy aging: a systematic review of the evidence. Nutrients. 2024 Aug;16(16):2721. DOI: 10.3390/nu16162721

5. Francis AJ, Sreenivasan C, Parikh A, AlQassab O, Kanthajan T, Pandey M, et al. Curcumin and cognitive function: a systematic review of the effects of curcumin on adults with and without neurocognitive disorders. Cureus. 2024 Aug;16(8):e67706. DOI: 10.7759/cureus.67706