Blog 5 of 6

By Terry Willard Clh, PhD

This material will be presented at the Kootenay Herb Conference on July 8^th, 2023 (https://herbconference.com/kootenay-herb-conference/).

This blog is the fifth in the series on Alzheimer’s disease (AD). We are going to cover medical treatment for AD and start looking at (W)holistic protocols.

Medical Treatment

According to modern allopathic medicine, there is currently no cure for Alzheimer’s disease, but there are medications available that can temporarily reduce the symptoms. Other support as list below, is also available to help someone with this condition, and their family, cope with everyday life.

The most prescribed medicines are:

Acetylcholinesterase Inhibitors (AChE inhibitors)
The primary function of these medications is to boost levels of acetylcholine in the brain, which is a chemical that permits nerve cells to communicate with each other. As of 2023, AChE inhibitors can only be prescribed by specialists such as neurologists or psychiatrists. GPs can also prescribe these medications on recommendation by a specialist or if they have expertise in their use.

The three primary AChE inhibitor medications—Donepezil, Galantamine, and Rivastigmine—are effective for those suffering from early to mid-stage Alzheimer’s disease. Recent guidelines recommend continuing on with these medications even in the severe stages of the disease, as they have been known to be helpful. While there is no difference in efficacy for how well these 3 medications work, some patients may react better to certain types or have fewer side effects. It is worth noting that AChE inhibitors may produce side effects such as nausea, vomiting, and loss of appetite. These side effects are often temporary and tend to disappear within two weeks of starting the medication.

Another medication used in the treatment of Alzheimer’s disease is Memantine. Unlike AChE inhibitors, Memantine does not operate by increasing acetylcholine levels in the brain. Instead, it suppresses the effects of an excess of glutamate, a chemical in the brain. This medication is ideal for people suffering from moderate to severe Alzheimer’s disease or who are unable to tolerate AChE inhibitors. It is also helpful for those who are already taking AChE inhibitors but have severe Alzheimer’s disease. Some temporary side effects of Memantine may include constipation, dizziness, and headaches.

It is advisable to read the patient information leaflet that comes with the specific medication or speak to the doctor to gain more information about possible side effects.

Treatments with Therapies and Activities

Medicines for Alzheimer’s disease symptoms are only one part of the care strategy for the person with dementia. Other treatments, activities, and support are just as important in helping people live well with dementia but are not curative nor reversing the symptoms.

Cognitive Stimulation Therapy

One promising therapy is cognitive stimulation therapy (CST), wherein individuals engage in group activities and exercises aimed at enhancing memory function and problem-solving capabilities. 

Cognitive Rehabilitation

Similarly, cognitive rehabilitation entails partnering with a skilled professional, such as an occupational therapist, and a close friend or family member to achieve a personalized goal (i.e., tasks to complete) related to daily activities or socialization. This method relies on activating the parts of the brain that remain functional to assist those that are failing to operate correctly.

Reminiscence and Life Story Work

Reminiscence and life story work are other therapeutic approaches that can effectively enhance wellbeing and mood. Reminiscence work encourages individuals to discuss past experiences, events, and interests, incorporating visual aids like photographs or music. Alternately, life story work serves to compile a scrapbook filled with mementos from an individual’s childhood to the present day, which can assist them when recalling memories.

In combination, these methods have been shown to foster greater emotional and mental stability in individuals living with dementia. 

Language and Puzzle Skills

It has been shown that learning a second language, especially after age 50, can dramatically decrease dementia and AD.^[1]

John Grundy, an assistant professor of psychology at Iowa State University, conducted a comprehensive review and analysis of the available evidence on the subject of bilingualism and Alzheimer’s disease in 2020. His findings provided compelling evidence that those who can speak two languages have a higher cognitive reserve—or capacity to ward off damage—than monolinguals. Specifically, he noted that bilinguals tend to show Alzheimer’s symptoms later than their single-language counterparts. This phenomenon is backed by multiple studies and is known as a “very robust finding” in the psychological literature. 

Learning another language increases neural connections in areas of the brain associated with memory, emotional regulation, and self-control. Additionally, these “bilingual brains” appear to be more diverse and better connected than monolingual brains, contributing to their increased resistance against Alzheimer’s spread and its adverse effects on cognition. 

Computer programs or apps for learning another language (such as Duolingo, Babbel, Mondly or Rosetta Stone) offer a great opportunity for older adults to take advantage of this cognitive protection by starting a productive habit of language learning late in life. 

Holistic Treatment of AD

The treatment of AD disease is similar in scope to other neurodegenerative conditions such as Parkinson’s disease. As AD is likely a condition that progresses slowly as a result of repeated insult and damage to the brain, preventative measures based on eating a healthy diet and following a healthy lifestyle are highly recommended for anyone with a family history of AD.  

Diet

Diet is an important factor in the development of AD. Eating the Standard American Diet (SAD), high in saturated and trans-fatty acids as well as low in dietary antioxidants, is quite bad for AD.

The SAD can increase levels of aluminum and help to transition metal ions into the blood and brain, both of which are known to cause oxidative damage and consequent neurological damage associated with AD. Poor dietary choices may also lead to inflammation of the brain, which can bring about neurological damage resulting in AD.^[2],[3],[4]

In comparison to the typical American diet, Mediterranean diets have been linked with a slower rate of cognitive decline as well as a reduced risk for cardiovascular illnesses. Numerous prospective studies have shown that Mediterranean diets are associated with lower cognitive decline, decreased risk of progression from mild cognitive impairment (MCI) to AD, lowered risk of developing AD, and even a lower death rate from AD among those already suffering from the disease.^[5],[6],[7]

The KetoFLEX 12/3 diet, as mentioned in blog post __ [hyperlink], has not only been shown to slow down the cognitive decline in AD, but it has also shown to aid in reversing it in some patients.

Research has demonstrated that the main dietary elements that reduce odds of getting AD include consuming omega-3 fatty acids from fish sources, monounsaturated fatty acids primarily obtained from olive oil and MCT oil (these seem to almost act as an agent to dissolve the plaque). The patient should limit the amounts of alcohol, but can have a little, particularly red wine, and increase the intake of non-starchy vegetables and fruits. It is believed that there is not any one single factor that provides protection against AD, but rather a combination of all these components working together.^[8],[9]

The Mediterranean and KetoFLEX 12/3 diets have a two-fold effect—reducing inflammation and improving insulin sensitivity—both of which may play an essential role in its ability to reduce AD. In a 4-year prospective study, the lower risk associated with these diets was not mediated by C-reactive protein, fasting insulin or adiponectin levels.^[10] Therefore, other dietary components must be at work in protecting against AD; these could include dietary compounds that directly impact β-amyloid formation or deposition. For example, polyphenols found in grapes, grape seed extract, and red wine have been shown to prevent β-amyloid formation and promote tau disassembly.^[11],[12] Animal studies involving radiolabeled grape polyphenols have also demonstrated their absorption into the brain after oral administration.^[13]

Surprisingly enough, simply eating celery (Apium graveolens) may offer significant protection against AD as well. Celery contains 3-n-butylphthalide (NBP), a unique compound responsible for both its characteristic odor and health benefits. In an animal model of Alzheimer’s disease, NBP treatment improved learning deficit as well as long-term spatial memory; it also significantly reduced total cerebral β-amyloid plaque deposition and lowered brain β-amyloid levels through a pathway that precludes β-amyloid formation. The researchers concluded that NBP “shows promising preclinical potential as a multitarget drug for the prevention and/or treatment of AD.”^[14]

The research on grape polyphenols and NBP contained in celery and other foods containing protective compounds against AD; this includes sources such as phenols and polyphenols which have only started being explored recently.^{[15],[16],[17],[18]} It is possible that these foods work in part due to the unique combination of protective compounds found in its components, which operate through numerous pathways to reduce AD risk and slow cognitive decline.

Nutrition is an essential factor in the cognitive function of the elderly population. Nutrient deficiency is becoming increasingly more common in this age group, making it likely that many cases of impaired mental functioning can be attributed to inadequate nutrition. 

Here’s a summary of optimal dietary choices:

• Mediterranean diet, KetoFLEX 12/3 diet, low carbohydrate diet to prevent CVD (cardiovascular disease)
• Emphasize antioxidant foods, e.g., garlic, onions, cruciferous vegetables, and foods rich in anthocyanidins, e.g., blueberries, huckleberries, elderberries, red and black grapes 
• Eating large amounts of fish or fish oils dramatically reduces speed of progression of dementia
• Emphasize foods rich in the biochemical building blocks of acetylcholine, e.g., free-range eggs, lecithin
• Avoid trans-fatty acids and hydrogenated fats
• Avoid all aluminum-containing foods or foods packaged in aluminum (e.g., various antacids, dolomite; aluminum cans, foil, and cookware)
• Emphasize artichokes to enhance liver metabolism

Eat “Brain Foods”—Dr. Uma Naidoo, a nutritional psychiatrist at Harvard Medical School, has a great acronym for a BRAIN FOODS:

• B: Berries and beans
• R: Rainbow colors of fruits and vegetables
• A: Antioxidants
• I: Include lean proteins and plant-based proteins
• N: Nuts
• F: Fiber-rich foods and fermented foods
• O: Oils
• O: Omega-rich foods
• D: Dairy (see comments in Blog 4)
• S: Spices

And good news for chocoholics: A 2020 study found that cocoa flavonoids, the ingredients in dark chocolate, can enhance episodic memory in healthy young adults.

Exercise

• Daily walks can cut the risk of developing dementia by over 50%.^[19]
• An observational study of 78,000 people aged 40 to 79 in Denmark found that participants who took 9,826 steps a day lowered their risk of developing dementia by 50%.
• Walking at a very brisk pace (more than 40 steps/minute) dropped the risk of later developing dementia by 57% while 3,800 steps/day reduced it by 25%.
• Activities like performing household chores regularly reduced dementia risk by 21%, spending time with family and friends daily decreased risk by 15%, and electric-current stimulation improved short-term memory recall by 50-65%.

Another study below is from South Korea.^[20]

• Suggests that 10 minutes of light to moderate exercise as little as three times a week can improve cognitive health.
  • The study observed 250,000 patients with mild cognitive impairments and six groups with different levels and frequencies of exercise.
  • Regular exercise was defined as either moderate physical activity at least five times per week or vigorous physical activity at least three times per week.

Those who never exercised had an 18% higher chance of developing Alzheimer’s; those who began exercising after their Mild cognitive impairment (MCI) diagnosis had decreased their likelihood of getting the disease by 11%.

• Exercise can increase brain-derived neurotrophic factor, cerebral blood flow, blood sugar regulation, and vascular stimulation.

Soleus Pushups

Lower leg blood pressure and strength can determine level of dementia. The use of soleus pushups increased number of mitochondria in the body, we can see that weakness in the calve muscles can be a strong indicator to brain function. 

The human vascular system is an intricately designed apparatus that functions as a “second heart,” pumping blood throughout the body and supplying vital nutrients and oxygen to all organs, tissues, and cells. The veins in our calves act as a reservoir for this blood when it isn’t immediately needed by the body’s various systems. These veins are known as venous sinuses. 

When physical activity causes the calf muscle to contract, the stored blood is pushed along the venous system towards the heart and brain. At the lower half of the back of your leg, there are two prominent muscles that facilitate this motion: the gastrocnemius and soleus. 

The gastrocnemius is a larger muscle located adjacent to the fibula (a small bone in the lower leg) which helps to point your toes and bend your knee in order to move forward. This muscle will often create a visible “bulge” when contracted. The soleus is smaller and sits on the outer edge of your calf; it too helps point your toes but not with as much strength as its larger counterpart. 

When both these muscles are contracted, they squeeze open pathways which help pump blood through our bodies effectively; however, any sort of weakness or atrophy in these muscles can lead to serious health issues like pooling, stroke, claudication, and even dementia. Therefore, it is important to ensure that our calf muscles remain strong and healthy so that we may continue to benefit from their capacity as a “second heart” within our body’s circulatory system.^[21]

In our next and final blog post in the AD series, we will be looking at supplements and a suggested protocol to follow. 

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^[1] Anderson JAE, Hawrylewicz K, Grundy JG. Does bilingualism protect against dementia? A meta-analysis. Psychon Bull Rev. 2020 Oct;27(5):952-965. doi: 10.3758/s13423-020-01736-5. PMID: 32462636.

^[2] Solfrizzi V, Panza F, Capurso A. The role of diet in cognitive decline. J Neural Transm. 2003;110:95–110.

^[3] Grant W.B, Campbell A, Itzhaki R.F, et al. The significance of environmental factors in the etiology of Alzheimer’s disease. J Alzheimers Dis. 2002;4:179–189.

^[4] Frolich L, Riederer P. Free radical mechanisms in dementia of the Alzheimer’s type and the potential for antioxidative treatment. Arzneimittelforschung. 1995;45:443–446.

^[5] Solfrizzi V, Panza F, Frisardi V, et al. Diet and Alzheimer’s disease risk factors or prevention: the current evidence. Expert Rev Neurother. 2011;11(5):677–708.

^[6] Frisardi V, Panza F, Seripa D, et al. Nutraceutical properties of Mediterranean diet and cognitive decline: possible underlying mechanisms. J Alzheimers Dis. 2010;22(3):715–740.

^[7] Agarwal P, et al “Association of Mediterranean-DASH intervention for neurodegenerative delay and Mediterranean diets with Alzheimer disease pathology” Neurology 2023; DOI: 10.1212/WNL.0000000000207176.

^[8] Solfrizzi V, Panza F, Frisardi V, et al. Diet and Alzheimer’s disease risk factors or prevention: the current evidence. Expert Rev Neurother. 2011;11(5):677–708.

^[9] Frisardi V, Panza F, Seripa D, et al. Nutraceutical properties of Mediterranean diet and cognitive decline: possible underlying mechanisms. J Alzheimers Dis. 2010;22(3):715–740.

^[10] Gu Y, Luchsinger J.A, Stern Y, et al. Mediterranean diet, inflammatory and metabolic biomarkers, and risk of Alzheimer’s disease. J Alzheimers Dis. 2010;22(2):483–492.

^[11] Wang Y.J, Thomas P, Zhong J.H, et al. Consumption of grape seed extract prevents amyloid-beta deposition and attenuates inflammation in brain of an Alzheimer’s disease mouse. Neurotox Res. 2009;15(1):3–14

^[12] Wang J, Santa-Maria I, Ho L, et al. Grape derived polyphenols attenuate tau neuropathology in a mouse model of Alzheimer’s disease. J Alzheimers Dis. 2010;22(2):653–661.

^[13] Janle E.M, Lila M.A, Grannan M, et al. Pharmacokinetics and tissue distribution of 14C-labeled grape polyphenols in the periphery and the central nervous system following oral administration. J Med Food. 2010;13(4):926–933.

^[14] Peng Y, Sun J, Hon S, et al. L-3-n-butylphthalide improves cognitive impairment and reduces amyloid-beta in a transgenic model of Alzheimer’s disease. J Neurosci. 2010;30(24):8180–8189.

^[15] Hamaguchi T, Ono K, Murase A, et al. Phenolic compounds prevent Alzheimer’s pathology through different effects on the amyloid-beta aggregation pathway. Am J Pathol. 2009;175(6):2557–2565.

^[16] Kim J, Lee H.J, Lee K.W. Naturally occurring phytochemicals for the prevention of Alzheimer’s disease. J Neurochem. 2010;112(6):1415–1430.

^[17] Williams P, Sorribas A, Howes M.J. Natural products as a source of Alzheimer’s drug leads. Nat Prod Rep. 2011;28(1):48–77.

^[18] Darvesh A.S, Carroll R.T, Bishayee A, et al. Oxidative stress and Alzheimer’s disease: dietary polyphenols as potential therapeutic agents. Expert Rev Neurother. 2010;10(5):729–745.

^[19] Del Pozo Cruz B, Ahmadi M, Naismith SL, Stamatakis E. Association of Daily Step Count and Intensity With Incident Dementia in 78 430 Adults Living in the UK. JAMA Neurol. 2022 Oct 1;79(10):1059-1063. doi: 10.1001/jamaneurol.2022.2672. Erratum in: JAMA Neurol. 2022 Sep 9;: PMID: 36066874; PMCID: PMC9449869.

^[20] Kim, Y.J., Han, KD., Baek, M.S. et al. Association between physical activity and conversion from mild cognitive impairment to dementia. Alz Res Therapy 12, 136 (2020). https://doi.org/10.1186/s13195-020-00707-1

^[21] Kleipool, Emma E F et al. “Orthostatic Hypotension: An Important Risk Factor for Clinical Progression to Mild Cognitive Impairment or Dementia. The Amsterdam Dementia Cohort.” Journal of Alzheimer’s disease : JAD vol. 71,1 (2019): 317-325. doi:10.3233/JAD-190402