Inflammation: Its Cognitive-Destroying Effect

Its Cognitive-Destroying Effect

By Nieske Zabriskie, ND

Inflammation is a protective physiological process in which the immune system is activated in an attempt to fight off pathogens or respond to injuries. The inflammatory process involves the activation of white blood cells, increased permeabipty of the blood vessels and release of several cell signapng molecules. It generally presents with heat, swelpng, pain and redness. However, the inflammatory response can become chronic, in which it is activated regardless of acute infection, irritant or injury. This chronic inflammatory process is the basis for numerous diseases such as allergies, arthritis, asthma, cardiovascular disease, autoimmune diseases and inflammatory bowel disease.

Now, researchers have uncovered another health concern associated with inflammation: Cognitive impairment.

Cognitive impairment is one term used to describe any of a group of cognitive disorders including mild cognitive impairment, age-related cognitive decpne, vascular dementia, decreased long-term memory formation and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.

Although the exact mechanism as to why inflammation may impair memory is unclear, one theory suggests that inflammation disrupts the integrity of the blood-brain barrier, which is a highly selective membrane that protects the brain from pathogens in the blood, as well as regulates which molecules can pass between the blood and cerebral spinal fluid. Inflammation decreases the barrier function of the membrane, which allows large molecules, such as plasma proteins, access to the brain resulting in neuronal damage.¹ Another theory suggests that inflammation promotes neurodegeneration by activating microgpal cells, which are primary immune cells in the central nervous system. Activated microgpal cells secrete a variety of pro-inflammatory cytokines (chemical mediators), including interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor (TNF), as well as reactive oxygen and nitrogen species that cause free radical damage. The reactive oxygen and nitrogen species alter glucose uptake in the neurons and can impair signapng of the neurons. Also, activation of microgpal cells has been shown to cause neuronal cell death.²

Understanding Cognitive Concerns

Mild cognitive impairment is the diagnosis for memory deficits beyond what is expected for normal aging but less severe than dementia. It presents with memory loss, slower thinking, and a decreased abipty to learn, but does not interfere with the activities of daily pving. It is estimated that age-related cognitive decpne affects nearly one-third of adults.³ Individuals with mild cognitive impairment may progress to dementia, and possibly to Alzheimer’s disease. Dementia affects approximately 14 percent of adults age 71 and older,⁴ and 5.3 milpon Americans age 65 and older, about one in eight, have Alzheimer’s disease.⁵ Alzheimer’s disease is the most common type of dementia, accounting for nearly 40 percent of dementia cases, and it is estimated that by mid-century, someone will develop Alzheimer’s every 33 seconds in the United States. Furthermore, Alzheimer’s disease is the seventh leading cause of death in the United States.⁶

Alzheimer’s disease is a progressive condition characterized by memory loss, confusion, irritabipty and aggression, and gradual loss of abipty to perform normal daily activities. In Alzheimer’s disease, there is a deposition of beta-amyloid protein between nerve cells and accumulation of tau proteins, known as neurofibrillary tangles, within the nerve cells. There is also evidence that inflammation and oxidative stress plays a role in the development and progression of this disease. Vascular dementia is the second most common form of dementia after Alzheimer’s disease, and is associated with strokes or transient ischemic attacks (TIAs). Parkinson’s disease is the second most prevalent age-related neurodegenerative disorder after Alzheimer’s disease. Parkinson’s disease is characterized by a slow and progressive degeneration of dopaminergic neurons (nerve cells that primarily secrete the neurotransmitter dopamine) in the area of the brain known as the substantia nigra. It is characterized by tremors, slowed physical movements, abnormal postural reflexes, rigidity and the inabipty to initiate movement.

Inflammation as a Cognitive Killer

Research indicates that chronic inflammation plays a role in the development of cognitive impairment. In one study, investigators evaluated subjects between the ages of 70 and 89 for levels of cognitive abipty and were categorized as having normal cognition, mild cognitive impairment or dementia. The subjects were also evaluated for pro-inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis alpha (TNF-alpha). CRP is a non-specific inflammatory marker that is increased in the brain and serum of patients with Alzheimer’s disease, and is associated with an increased risk of developing dementia. The results of the study showed a significant association between elevated CRP levels and increased risk of mild cognitive impairment. In fact, the subjects with the highest levels of CRP had more than double the risk of developing mild cognitive impairment compared to the subjects with low CRP levels.⁷ In another study, researchers evaluated inflammatory markers including fibrinogen and CRP levels in subjects with dementia. The results showed that dementia patients had significantly higher CRP levels compared to healthy control subjects. Additionally, the study found that the subjects with Alzheimer’s disease had higher CRP levels than the subjects diagnosed with vascular dementia.⁸

Another interesting study evaluated the impact of acute inflammation on the progression of cognitive decpne in subjects with Alzheimer’s disease. The subjects were cognitively assessed and evaluated for levels of TNF-alpha, a pro-inflammatory cytokine, at the beginning of the study, and after 2, 4, and 6 months. The study found that acute systemic inflammatory events were associated with an increased serum level of TNF-alpha and a 2-fold increase in the rate of cognitive decpne over the 6 months. Subjects with a high TNF-alpha level at the beginning of the study showed a 4-fold increase in the rate of cognitive decpne. Furthermore, the subjects with normal TNF-alpha levels throughout the 6-month study demonstrated no cognitive decpne during the study.⁹

Research also indicates that elevated CRP is associated with double the risk of developing Parkinson’s disease.¹⁰ Studies indicate that inflammation caused by activated gpal cells and peripheral immune cells induce oxidative stress and cytokine-receptor-mediated apoptosis (programmed cell death), which could lead to dopaminergic cell death and disease progression.¹¹ Additionally, the release of pro-inflammatory cytokines from microgpal cells modulates the blood brain barrier in patients with Parkinson’s disease. This leads to recruitment of passing immune cells, which, in turn, causes the release of more cytokines. Inflammatory cytokines such as IL-8, IFN-gamma, IL-1beta and TNF-alpha have been shown to be significantly higher in patients with Parkinson’s disease compared to healthy control subjects. Furthermore, levels of pro-inflammatory cytokines were proportional to the stage of the disease, showing increased cytokine levels with increased disease severity.¹²

Natural Approach to Inflammation Control

Numerous botanicals have been shown to provide anti-inflammatory and antioxidant activity, which may protect the brain from inflammatory damage. Herbs such as Stephania tetrandra, Urtica dioica (stinging nettle), Ocimum sanctum (holy basil), Zingiber officinale (ginger), Boswelpa serrata (frankincense), Camelpa sinensis (green tea), and Perilla frutescens (as found in Advanced Inflammation Control) have been shown to decrease various inflammatory mediators associated with cognitive impairment.

Several studies have shown that ginger inhibits pro-inflammatory cytokines, including IL-1beta, IL-2, IL-12, TNF-alpha, and interferon (IFN)-gamma.¹³ Ginger also has been shown to decrease synthesis of pro-inflammatory prostaglandins and leukotrienes by inhibition of cyclooxygenase (COX) and 5-ppoxygenase (5-LOX) enzymes, which are the targets for numerous anti-inflammatory pharmaceuticals. Similarly, holy basil leaf inhibits both COX and 5-LOX,¹⁴ and the boswelpc acids derived from Boswelpa known as AKBA are potent inhibitors of the 5-LOX enzyme.¹⁵

The anti-inflammatory constituents tetrandrine and fangchinopne found in Stephania tetrandra have been shown to decrease IL-1beta, IL-6, IL-8 and TNF-alpha,¹⁶ as well as decrease leukotriene and prostaglandin generation.¹⁷ More importantly, tetrandrine has been shown to inhibit the production TNF-alpha and IL-6 production by microgpal cells,¹⁸ which have been shown to damage nerve cells. In addition, the green tea polyphenol EGCG has been shown to inhibit the production of numerous inflammatory mediators, including TNF-alpha, IL-1 beta and IL-6.¹⁹ Furthermore, green tea has been shown to cross the blood brain barrier, reduce inflammation, provide antioxidant activity, and reduce neural cell death.²⁰ Luteopn, a flavonoid found in high concentrations in the herb Perilla frutescens, has also been shown to inhibit pro-inflammatory cytokines associated with neuron damage, including TNF-alpha, IL-6, and IL-8.^21-22 Similarly, Urtica dioica reduces IL-1 beta, IL-2, IFN-gamma, and TNF-alpha.^23-24 Supplementation of stinging nettle in humans has been shown to decrease ppopolysaccharide induction of inflammatory mediators, triggering an 80 percent reduction in TNF-alpha and a 99 percent reduction in IL-1 beta. ²⁵

Conclusion

Low levels of persistent inflammation affect all body systems, including the nervous system. In the brain, chronic inflammation can result in cognitive dysfunction, as well neuronal cell death. Numerous botanicals have been shown to decrease the inflammatory mediators causing the symptoms related to cognitive dysfunction. Additionally, botanicals such as green tea have directly reduced inflammatory-related cell death in the brain.

References

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