Preventing Alzheimer’s Disease and Cognitive Decline with Botanicals, Nutritional Compounds & Diet

Compiled by John G. Connor, M.Ac., L.Ac. Edited by Barbara Connor, M.Ac., L.Ac.

Table of Contents    
Introduction    
Understanding Alzheimer’s Disease and Other Neurological Diseases    
Beneficial Herbs and Supplements for Cognition and Memory    

Other Beneficial Herbs, Foods and Botanicals

Introduction:
This is a compilation of our own research on the subject as well as being a summary of an article by Donald Yance entitled: “Neurological Health.  Botanical and Nutritional Intervention for the Prevention and Treatment of Alzheimer’s Disease and other Dementias” in which he includes 315 references to the scientific literature.  Barbara and I hope you find this article helpful and useful in maintaining good mental acuity. 

Understanding Alzheimer’s Disease and Other Neurological Diseases:
Characteristics of Alzheimer’s disease :     
Alzheimer’s disease (AD) is a disease of aging characterized by plaque formation, fibrous tangles, nerve cell death, mitochondrial impairment, neuroendocrine decline, hormonal disruption, inflammation and oxidative stress – all of which contribute to changes in the brain, and lead to neuronal degeneration and cognitive impairment.

Amyloid plaque:   
The abnormal build-up of amyloid plaque in the brain forms the basis for the damage caused by Alzheimer’s disease.  In a normal, healthy brain, amyloid is produced, broken down, and then cleared away to prevent it from piling up between brain cells.  In a brain under siege by Alzheimer’s disease, the amyloid accumulates and hardens into insoluble plaques that researchers suspect are neurotoxic and may take their toll on mental functioning by upsetting nerve cell function, producing inflammation, and killing nearby cells.

Risk factors:
The most important risk factors for Alzheimer’s disease are family history of Parkinsonism, hypothyroidism, and a history of head trauma with loss of consciousness.

Chronic stress has been shown to increase the risk and severity of neurological diseases.  In one study persons with a high level of distress proneness were 2.7 times more likely to develop Alzheimer’s disease than those not prone to distress.  The results of this study support the hypothesis that distress proneness is associated with increased risk of dementia and suggest that neurobiologic mechanisms other than Alzheimer’s disease pathology may underlie the association.

Increased cortisol secretion has been reported in Alzheimer’s disease.  Increased cortisol levels affect hippocampal neuronal survival and potentiate beta-amyloid toxicity.  Conversely, DHEA and its sulfate antagonize noxious glucocorticoid effects and exert neuroprotective properties.

Advanced glycation end products:
The formation of advanced glycation end products happens in everyone and is a major factor in the aging process itself.  Elevated insulin and glucose can lead to the formation of advanced glycation end products.  Advanced glycation end products-induced free radicals activate the pro-inflammatory cytokine TNF-alpha (tumor necrosis factor-alpha), known to be elevated in the elderly.  TNF-alpha is know to be particularly high in inflammatory disease of the central nervous system (e.g., Alzheimer’s disease, multiple sclerosis, ischemia) and is believed to promote neurodegeneration.  Brain autopsies of Alzheimer’s disease patients show signs of significant oxidative damage induced by free radicals, and point to the fact that advanced glycation end products are a major contributing cause of Alzheimer’s disease.
Older women with low estradiol levels are more likely to experience a decline in global cognitive function and verbal memory.

Homocysteine
:
People with high blood levels of homocysteine have twice the average risk of developing Alzheimer’s disease.  Homocysteine is created when the body uses the amino acid, methionine, for methylation.  Normally homocysteine is converted back to methionine, or used to create cysteine and other useful substances.  If these conversions are blocked homocysteine accumulates leading to a host of negative reactions.

Homocysteine, which damages blood vessels, nerves, and specifically mitochondria, has been linked to heart attacks, strokes, cancer (particularly colon, breast, and prostate cancer), Alzheimer’s disease and other neurological diseases, depression, birth defects, gout, cervical dysplasia, erectile dysfunction and rheumatoid arthritis.

Efficient conversion of homocysteine requires certain nutrients, which neutralize homocysteine’s toxicity by transforming it into useful substances.  The most well-studies nutrients are folic acid, vitamin B12, and vitamin B6.  Choline, betaine (TMG), creatine, riboflavin, zinc, magnesium and other nutrients also help detoxify homocysteine.

Studies show that folate supplements (1-5 mg/day) have a significant impact on reducing homocysteine levels.  Increasing your intake of fruits and vegetables, which has numerous other benefits, and/or supplementing with B vitamins, can help convert homocysteine to other amino acids that are not harmful.  Homocysteine levels can rise when people eat a diet heavy in animal protein and/or few fruits or leafy vegetables.

Glutathione
:
   
Glutathione is the most abundant low-molecular-weight thiol and glutathione disulfide is the major redox couple in animals and humans.  Glutathione deficiency contributes to oxidative stress, which plays a key role in aging and the pathogenesis of many neurological diseases, including seizure, Alzheimer’s disease, and Parkinson’s disease.  Animal and human studies demonstrate that adequate protein nutrition (non-denatured whey protein concentrate being the best) is crucial for the maintenance of glutathione homeostasis.

CRP – C-reactive protein
:
           
The production of C-reactive protein is an essential part of the inflammatory process and the measurement of this substance reflects the level of inflammatory activity deep within the body.  In one study the more CRP that subjects had at the start of the study, the higher their risk of developing Alzheimer’s disease.

Many natural compounds, including polyphenols, red yeast rice extract, vitamin E, omega-3 fatty acids, as well as a vegetable diet with fish, have been found to lower CRP.  Normalizing DHEA levels and mediating inflammation with adaptogenic remedies is an effective way to normalize elevated CRP.

Aluminum, Copper, Iron and Alzheimer’s disease:
           
In one study aluminum or copper may independently initiate inflammatory or oxidative events that contribute to Alzheimer’s disease.
Higher iron loads increase oxidative stress, leading to Alzheimer’s disease.
            
Zinc and molybdenum are effective at lowering copper in the body.  Plant phenols, isothiocyanates and sea vegetables reduce heavy metal and mineral toxicity as well.  

Beneficial Herbs and Supplements for Cognition and Memory
Panax ginseng:   
Panax ginseng improves overall mental performance, particularly during prolonged stress and helps with poor concentration due to fatigue or old age.  It is also considered a general anti-aging tonic for the elderly.

Panax ginseng was recently shown to possess neurotrophic (improves neurological health) and neuroprotective properties, which may be useful in preventing various forms of neuronal cell loss, including the degeneration seen in Parkinson’s disease.

In one animal study ginseng and schisandra extracts taken together suggested that they might be useful for treating physiological aging and age-related memory deficits in humans.

 Panax ginseng possesses a strong protective effect against neurotoxicity by preventing carboxyl-terminal fragments-induced neurofibrillary tangles.  These fragments have been found in plaques, microvessels and the neurofibrillary tangles in the brains of Alzheimer’s disease patients.

American ginseng:
 
 American ginseng is a neurological protectant; it improves memory and learning, and has been shown to improve ADHD.  American ginseng extract has also been shown to improve brainstem neuronal activities, insulintrophic effects, free radical quenching activity and cerebral circulation, which contribute to its neuro-protective and anti-aging effects.

Eleuthero:
   
Eleuthero demonstrates favorable effects on various human functions, including visual acuity, color differentiation, hearing, fatigability, thinking association with motor activity.  It also possesses a capacity of displaying a normalizing effect regardless of the physiological abnormalities caused by damaging influences, e.g. normalization of blood pressure in patients with both elevated or lowered blood pressure; normalization of blood sugar levels in hyper-or hypoglycemia.
Eleuthero has been shown to improve learning and memory.  Several animal and human studies have demonstrated that eleuthero preserves neurological health, inhibits oxidative damage and extends life span.

Rhodiola:
     
Rhodiola rosea extract enhances immunity, increases capacity for exercise, increases the activity of superoxide dismutase, decreases serum lipids and modulates the ratio of cAMP and cGMP.  It also has antimutagenic and antioxidant properties, enhances memory and is an antidepressive agent.

Rhodiola rosea extract has also been shown to enhance central nervous system activity, improve learning and memory, improve mood, act as a neuro-enhancer and inhibit aging of the brain.

Ashwagandha:   
Ashwagandha root has been shown to enhance learning and memory.  Withanolide A (WL-A), isolated from ashwagandha root, regenerates neuritis and reconstructs synapses in severely damaged neurons.

Ashwagandha root extract has been shown to increase acetylcholine receptor capacity, which might partly explain the cognition-enhancing and memory-improving effects of extracts observed in animals and humans.

 Combined with ginseng, it improves psychomotor skills, protects cognition, and, combined with mumie, inhibits dementia/Alzheimer’s disease.  Ashwagandha and mumie together showed a GABA-like effect, as well as an acetylcholine receptor enhancing effect. These effects explain how ashwagandha may enhance memory and inhibit age-related mental decline

Rhaponticum:
         
Rhaponticum carthamoides extract (RCE) improves sleep, appetite, moods, mental and physical state, and the functional ability of humans under working conditions.  It builds lean muscle, reduces body fat, improves mental acuity, relieves depression, and delays the effects of aging.           

RCE helps prevent loss of lean muscle tissue during the time of intensive training, thereby enhancing middle and long distance runner’s performance.  This same effect is vitally important for the prevention of age-related catabolic increases that contribute to mental decline.

Schisandra seed and fruit:
   
It has recently been demonstrated that Schisandra berry fortifies mitochondrial antioxidant status. Given the indispensable role of the mitochondrion in generating cellular energy, the linking of Schisandra to the safeguarding of mitochondrial function provides a biochemical explanation for its Qi invigorating action.

Schisandra seed improves reading comprehension, aptitude and speed.  Schisandra fruit possesses therapeutic potential against oxidative neuronal damage induced by excitotoxin.

  The results of another study suggest that Schisandra based herbal preparations have some protective characteristics against neuronal cell death and cognitive impairments often observed in Alzheimer’s disease, stroke, ischemic injury and other neurodegenerative diseases.
           
Other primary adaptogens that have been shown to improve memory and learning and to inhibit neurological aging, include Aralia manchuria root and mumie.

Poria cocus:     
Poria cocus, used in combination with other herbs, recently demonstrated an ability to improve learning and memory, and inhibit dementia in animals.

He shou wu:     
Many studies have verified the brain protecting and enhancing effects of he shou wu, as well as lipid modulating and age reducing effects.

Ginkgo biloba:
The therapeutic efficacy of Ginkgo biloba extract (GBE) for AD, in placebo controlled clinical trials, is reportedly similar to currently prescribed drugs such as tacrine or donepezil and, importantly, undesirable side effects of ginkgo are minimal. (Fu et al 2011)

There is consistent evidence that chronic administration of GBE improves selective attention, some executive processes and long-term memory for verbal and non-verbal material. (Kaschel et al 2009)

The results of another study, involving following over 3,500 subjects over the age of 65 for over 13 years, found that treatment with ginkgo extract increased the probability of survival, by 25%, in this elderly population. (Dartiques et al 2007)

In a recent multicenter, randomized, controlled trial of 120 mild cognitive impairment (MCI) patients, patients were randomly assigned to the GBE group and control group. The patients in the treatment group took GBE tablets 3 times a day, 19.2 mg each dose. After 6 months of treatment, the scores of the logical memory test and nonsense picture recognition were increased significantly in the treatment group, while the scores of the two tests from the control group had no statistically significant difference. After treatment, the positive rate of nonsense picture recognition was 55.17% in the treatment group, which was significantly higher than that of the control group at 32.73%. The efficacy rate of logical memory was 58.62% in the treatment group, also higher than 38.18% in the control group. GBE showed good efficacy in promoting episodic memory function in MCI patients. (Zhao et al 2012)

Ginkgo biloba standardized extract can protect against intermittent hypoxia-induced memory impairment, oxidative stress and neuronal DNA damage, possibly through multiple mechanisms involving its potential anti-oxidative effect.  (Abdel-Wahab et al 2012) 

Extensive studies on G. biloba extracts showed their ability to protect brain neurons from oxidative stress (Oyama et al 1996) and to inhibit apoptosis in cell culture. (Xin et al 2000)  Ginkgo can protect brain cells during a stroke, and triggers a cascade of events that neutralizes free radicals known to cause neuron cell death. (Saleem et al 2008)

GBE exerts a neuroprotective effect against ischemic brain injury through an anti-apoptotic mechanism. Parvalbumin is a calcium buffering protein that plays an important role in modulating intracellular calcium concentration and regulating apoptotic cell death. The results of this study demonstrate that the maintenance of parvalbumin expression is associated with the neuroprotective function of GBE against neuronal damage induced by ischemia. (Sung et al 2012)
 
Bacopa:         
Bacopa has been clinically proven to improve memory and mood in Alzheimer’s disease, possessing antidepressant and antioxidative actions.  Bacopa recently demonstrated an ability to prevent aluminum neurotoxicity, a known contributor to dementia and Alzheimer’s disease.

A double-blind placebo-controlled independent group study found that Bacopa monnieri significantly improved performance on the ‘Working Memory’ factor, more specifically spatial working memory accuracy. The current study provides support for the two other published studies reporting cognitive enhancing effects in healthy humans after a 90 day administration of the Bacopa monnieri extract. (Stough et al 2008)

Research evidence clearly indicates that Bacopa monnieri and Centella asiatica possess neuroprotective properties, have nootropic (enhancing cognition and memory) activity with therapeutic implications for patients with memory loss. (Shinomol et al 2011)

Bacopa has been clinically proven to improve memory and mood in AD, possessing antidepressant and anti-oxidative actions. (Chowdhuri et al 2002, Roodenrys et al 2002 and Sairam et al 2002)

In addition, bacopa exerts potent, free radical scavenging effects, ridding the body of various toxins and heavy metals. Bacopa recently demonstrated an ability to prevent aluminum neurotoxicity, a known contributor to dementia and AD. (Jyoti et al 2006)
 
 Cigarette smoke induces hsp70 expression and decreases neurons in the brain.  Administration of bacoside A (which is found in Bacopa) prevented expression of hsp70 and neuronal apoptosis during cigarette smoking, protecting the brain from the toxic effects of cigarette smoking.

Gotu kola: 
Gotu kola was researched as a memory enhancer and brain protector against oxidative stress in an animal study. These data suggest that gotu kola has the propensity to modulate both endogenous and neurotoxicant induced oxidative impairments in the brain and may be effectively employed as a neuroprotective adjuvant to abrogate oxidative stress in vivo. (Shimomol et al 2008)

Research evidence clearly indicates that Bacopa monnieri and Gotu kola possess neuroprotective properties, have nootropic (enhancing cognition and memory) activity with therapeutic implications for patients with memory loss. (Shimomol et al 2011)

The data indicate that Centella asciatica extract can impact the amyloid cascade altering amyloid beta pathology in the brains of PSAPP mice and modulating components of the oxidative stress response that has been implicated in the neurodegenerative changes that occur with AD. (Dhanasekaran et al 2008)

A recent study found the Asiatic acid, one of the main constituent triterpenes found in Gotu kola, dramatically reduced the build up of amyloid plaque, thus reducing the onset of AD. (Patil et al 2010)

Curcumin:       
Curcumin has been shown to prevent the accumulation of amyloid beta, and to reduce heavy metal toxicity in the brain.  When curcumin was studied in vitro it was found to inhibit amyloid beta aggregation better than ibuprofen or naproxen, which are being evaluated in the treatment of Alzheimer’s disease.

Resveratrol, grape seed and skin:
       
 Moderate intake of red wine, rich in many polyphenols, including resveratrol, has demonstrated significant protection against Alzheimer’s disease, neuropathology, and cognitive deterioration in general.  Resveratrol may also be effective in fighting other human amyloid-related diseases, such as Huntington’s and Parkinson’s disease.
           
Resveratrol appears able to inhibit certain age-promoting genes that become activated and induce obesity and diabetes..

Quercetin:           
Quercetin is a flavone found in apples, onions, broccoli, eucalyptus, green, black and red tea, and blue-green algae.  It possesses anti-oxidative, anti-inflammatory, anti-allergenic, and anti-cancer actions, and appears to protect brain cells against oxidative stress, a tissue-damaging process associated with Alzheimer’s and other neurodegenerative disorders.  A new study showed that brain cells treated with quercetin had significantly less damage than those treated with vitamin C or not exposed to any antioxidants.

Green Tea
:    
 A recent study found that elders who drink green tea regularly may have sharper minds than those who don’t drink green tea.  Those who reported drinking the most green tea were least likely to show cognitive impairment based on their test scores.

Epigallocatechin-3-gallate (EGCG) is a major antioxidant in green tea.  EGCG decreases production of the protein beta-amyloid, which is related to Alzheimer’s disease and can accumulate abnormally in the brain, leading to nerve damage and memory loss.  EGCG’s ability to prevent beta-amyloid buildup requires much higher amounts than what would normally be consumed, so drinking green tea alone may be insufficient.  In addition, the amount of EGCG a patient needs to fight Alzheimer’s disease is much higher than that found in green tea.

Green tea also inhibits Alzheimer’s disease by inhibiting NF-kappa beta, a pro-inflammatory protein, by reducing oxidative neuron damage, reducing heavy metals and by enhancing oxygen uptake,
Green tea has also been found to inhibit Huntington’s disease.  ECGC potently inhibits the aggregation of mutant Huntington protein.

Other Beneficial Herbs, Foods and Botanicals:
Grape seed and skin and  pomegranate juice:
Certain herb and fruit concentrates rich in polyphenols, e.g. grape seed and skin (found in Botanical Treasures), pomegranate extract (found in Cell-Guardian) provide neuroprotection in adult animal models of ischemia and Alzheimer’s disease. 

Isothiocyanates:
Isothiocyanates (found in Cell-Guardian), from cabbage sprouts, were also recently shown to inhibit neurological disease as well.  This most likely occurred through the enhancement of the brain levels of glutathione, reducing oxidative stress and inhibiting amyloid protein A-beta.

Common Sage:           
The results of one study indicate the efficacy of Common sage (S. officinalis) extract in the management of mild to moderate Alzheimer’s disease. 

High fruit and vegetable intake:           
Higher intake of fruits, vegetables and omega-3 rich fish protect against oxidative damage, thus lower the risk of cancer, cardiovascular disease and the occurrence of Alzheimer’s disease.  One study found that fruit and vegetable juices appear to play a significant role in delaying the onset of Alzheimer’s disease, particularly among those who are at high risk for the disease.

Another recent study confirmed that increased vegetable consumption is protective against cognitive decline.

The Mediterranean diet:           
One study found that close adherence to the Mediterranean diet was significantly associated with a reduced incidence of Alzheimer’s disease.

EPA and DHA fatty acids: 
Boosting levels of DHA in the blood eith4er by eating about three fish-meals each week and/or supplementing the diet with a DHA/EPA-rich fish oil, can reduce the risk of Alzheimer’s disease by one-half in elderly men and women.  Clinical studies with DHA/EPA have shown improvement in Alzheimer’s disease, senile dementia, cerebral thrombosis and many cardiovascular disease.  They have also been shown to prevent hyperlipidemia, hypertension and cancer.

 A recent human study demonstrated that fish oil supplementation slows down Alzheimer’s disease.

Creatine:           
A recent human study found that creatine supplementation (5 gm/day) given to people suffering from Alzheimer’s disease showed significant enhancement in brain energy capacity, improving brain performance.

Lipoic acid and Carnosine:           
Both lipoic acid and carnosine have been shown to rejuvenate aging cells, causing them to regain their youthful state.  Glycosylation, one of the cardinal processes of aging, is inhibited by both lipoic acid and carnosine.

            In experiments, treatment with carnosine was found to reduce or completely prevent cell damage caused by beta amyloid.

            Lipoic acid (alpha-lipoic acid) has several beneficial effects on the whole body, especially for the liver, eyes, brain, pancreas, kidneys and skin.  Its function as a coenzyme is essential for ATP production and cell efficiency.  Another important benefit of its use is that lipoic acid chelates heavy metals such as aluminum.

Alpha Glyceryl Phosphoryl Choline (A-GPC): 
Choline, an essential component of phospholipids, is a building block for acetylcholine; a major neurotransmitter of the central nervous system, its decline is believed to be a contributing cause of Alzheimer’s disease.

Carnitine and Acetyl l-carnitine:     
  Both carnitine and acetyl l-carnitine (ALC) enhance energy production by facilitating the transport of fatty acids into the energy-producing units in the cells.  In two animal studies acetyl l-carnitine significantly reversed age-associated mitochondrial decay.  It increased cellular respiration, membrane potential, cardiolipin levels, and mitochondrial health.

            Several controlled clinical studies in Europe show that ALC slows down the natural course of Alzheimer’s disease in many important respects.

Glutathione:           
Glutathione deficiency contributes to oxidative stress, which plays a key role in aging and the pathogenesis of many disease including Alzheimer’s disease and Parkinson’s disease. 

Undenatured whey protein, rich in cysteine, , along with magnesium-glutamine chelates, lipoic acid, NA cysteine , isothiocyanates , selenium schisandrins in Schisandra and silibinin in milk thistle, all play a role in enhancing healthy cellular glutathione levels in the body.

CoQ10:            CoQ10 has been shown to improve learning and memory deficits by inhibiting oxidative stress and improving levels of ATP.

Boron: 
Boron may play a role in human brain function and cognitive performance.

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Compassionate Acupuncture and Healing Arts, providing craniosacral acupuncture, herbal and nutritional medicine in Durham, North Carolina. Phone number 919-309-7753.

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