Alzheimer’s disease

What is Alzheimer’s Disease?

Alzheimer's disease is one of the most common causes of disability in the aging population. It is a neurological disorder that progressively causes shrinkage of brain tissues and early neuronal degeneration. It is also the commonest form of dementia, resulting in dysfunctions in memory, social skills, thinking, and behavior. Globally, over 30 million people over age 65 suffer from Alzheimer's disease.
Patients suffering from Alzheimer’s disease initially display signs of poor memory such as inability to recall recent events. With disease progression, Alzheimer’s disease can cause severe impairment of memory. Eventually, the patient will be unable to carry out even basic activities of daily life such as clothing themselves, eating, emptying their bowels, and so on.

What is the underlying etiology of Alzheimer’s Disease?

The underlying etiology for Alzheimer’s disease is still not understood clearly. But, most specialists in this field believe that a dysfunction in the brain proteins is responsible for a chain of events that cause neurons to die and disrupt brain function. Studies indicate that Alzheimer’s disease has a multifactorial etiology, with genes, lifestyle, and environment contributing to the development of Alzheimer’s disease.
In rare cases, a genetic mutation makes a person susceptible to developing Alzheimer’s. In such mutation-induced cases, the onset of symptoms occurs early and the progression is also more rapid.
Usually, the disease begins in the part of the brain where memory is formed. But the actual disease process starts long before the patient develops symptoms. In the advanced stage of the disease, the brain becomes remarkably atrophied. Mainly, two proteins have been implicated in Alzheimer’s disease, Beta-amyloid proteins, and Tau proteins.

Plaques

Beta-amyloid is a primary structural protein that can be toxic to neurons if they cluster in the brain. Clusters of beta-amyloid fragments can disrupt the process of communication between cells. When these clusters form closely together, why form a larger structure known as amyloid plaques.

Tangles

For the proper functioning of the neurons, tau proteins are integral to transport nutrients and other crucial matters to internally support the neurons. When tau proteins reorganize into tangles called neurofibrillary tangles, they can result in Alzheimer’s disease. These tangles can cause disruption of the transportation of the nutrients to the neurons, resulting in their death.

Risk Factors of Alzheimer’s Disease

There are several factors that can increase your risk for Alzheimer’s disease, which have been listed below.

Age

Advanced age is the most important risk factor for the development of dementia, including Alzheimer’s disease. However, Alzheimer’s is not a sign of aging and is not a normal finding.

Genetics

If a close member of your family has previously been diagnosed with Alzheimer’s, the risks of Alzheimer's are higher than the general population.

Down syndrome

Patients born with Down syndrome, a chromosomal disorder, are highly susceptible to developing Alzheimer’s disease at an early age. Usually, they develop Alzheimer’s in the first or second decade of life.

Traumatic Brain Injury

A history of severe head trauma can increase your risk of developing Alzheimer’s disease. Studies have shown that there is an increased incidence of Alzheimer’s in people with an incident of traumatic brain injury.

Alcohol consumption

Alcohol consumption can cause permanent changes to the brain. Large-scale studies have shown that alcohol usage is associated with dementia.

Insomnia

Sleep disorders, such as insomnia, have also been associated with increased incidences of Alzheimer’s in large-scale studies.

Lifestyle

Risk factors for coronary vascular diseases such as obesity, hypertension, high cholesterol, smoking, and diabetes have also been linked to Alzheimer’s disease.

Symptoms and Signs

It is common knowledge that the main symptom of Alzheimer’s disease is memory loss. In the early stages of the disease, patients have problems with recalling recent memories and events. With disease progression, issues with memory and cognition decline.
Suspicion of dementia initially arises from close friends or family members when the symptoms worsen enough to become noticeable. Pathological changes to brain tissues presents clinically as follows.

Memory Problems

As memory loss worsens with Alzheimer’s disease, people have issues with daily communication such as forgetting conversations, misplacing things often, getting lost in familiar areas, and having issues with naming objects or thought expression.

Personality Changes

Alzheimer’s can drastically alter a person’s personality and behavior. A previously cheerful personality may change to a depressive disorder while also displaying a lack of apathy, mood swings, and social withdrawal.

Difficulty making decisions

Patients with Alzheimer’s have difficulty in making sound judgments and decisions. For instance, the patient may behave out of character for social norms such as walking in the rain or laughing during a funeral.

Difficulties with familiar tasks

Alzheimer’s can disrupt a person’s ability to perform familiar activities such as cooking, driving, playing games, and so on. As the disease progresses, the patient may lose the ability to perform daily activities such as dressing themselves and may even neglect their hygiene.

Problems with reasoning

Abstract thought and concepts are extremely difficult for people with Alzheimer's disease due to problems with concentration. Patients may also have difficulties in performing multiple tasks at the same time. Daily activities essential for survival such as management of finances can be an impossible feat for patients with Alzheimer’s.

How is Alzheimer’s Disease Diagnosed?

Most patients are alerted regarding their symptoms by a close friend or family member, after which the patient often seeks medical attention. Further tests must be performed to confirm the diagnosis of Alzheimer’s. These tests may include an assessment of a patient's memory and cognitive skills, and other imaging tests. Imaging and laboratory tests are essential to rule out differential diagnoses for Alzheimer’s. However, a confirmatory diagnosis of Alzheimer’s is usually only after the patient’s death as the histopathological examination of brain tissue shows characteristic changes such as neurofibrillary tangles and amyloid plaques.

• Physical Examination: In order to rule out other possible causes of dementia, the doctor will examine your reflexes, gait, muscle strength and tone, cranial nerve functions, balance, and coordination.
• Laboratory investigations: While blood tests cannot confirm the diagnosis of Alzheimer’s, they are essential to rule out infections, tumors, or vitamin deficiencies, all of which may result in similar symptoms as Alzheimer’s. In some unusual cases, an evaluation of cerebrospinal fluid may also be done.
• Neurological Testing: Mental status examination includes assessment of reasoning skills, memory, and cognition. The test compares the ability to perform simple cognitive and memory-based tasks with other people of similar age without any pathological conditions.
• Imaging studies: Brain scan with MRI or CT is key to making a diagnosis of Alzheimer’s. These imaging studies can also help identify other causes of change in mental statuses such as ischemic stroke, hemorrhage, tumors, or trauma. Brain shrinkage and areas of dysfunctional metabolism can be visualized via imaging studies. Newer imaging modalities using PET scan, amyloid PET imaging, and Tau PET imaging are also being researched for their role in diagnosing Alzheimer’s.
• Plasma Aβ: Plasma Aβ is a blood test used to further strengthen the diagnosis of Alzheimer’s. It is a newly certified test in the US and is available currently.
• Genetic Tests: Although genetic testing does not fall under routine evaluation for Alzheimer’s, those with first-degree relatives suffering from Alzheimer’s may undergo genetic tests.

What Are the Complications of Alzheimer’s?

The complications associated with Alzheimer’s are similar to the clinical presentation. Issues with memory, language, and judgment can all complicate the patient’s life and even impact their ability to seek or receive treatment. Inability to communicate pain, symptoms, or follow treatment may also worsen the disease course.
In the final stages of the disease, brain atrophy and cellular changes can impact normal functioning. The patient may lose the ability to control bowel and bladder movements, and may also have difficulties with swallowing. Additional problems include concomitant infections, an increase in incidences of falls, malnutrition, dehydration, and bowel changes.

Can Alzheimer’s be Prevented?

Unfortunately, current evidence suggests that preventing Alzheimer's disease is not possible. But, avoiding the risk factors associated with Alzheimer’s may be beneficial to modify the disease course and decrease the likelihood of suffering from Alzheimer’s with increasing age. By practicing a healthy lifestyle such as daily exercising, consuming a diet rich with vegetables and fruits, regular health checkups, keeping blood pressure and cholesterol levels in control, avoiding harmful recreational agents such as alcohol or cigarettes may all help in preserving memory and cognitive function later in life. Furthermore, taking part in activities that require reasoning and involvement of higher mental functions such as playing chess, solving maths problems, or playing challenging games can also help preserve mental functions with increasing age.

Treatment of Alzheimer’s Disease

Drugs that are currently being used to treat Alzheimer’s help with the symptoms. They do not modify the disease course or cure the condition. Mainly, two types of medications are currently prescribed for Alzheimer’s.

Cholinesterase inhibitors

In Alzheimer’s disease, there is a depletion of acetylcholine, which is a neurotransmitter, that has been implicated in the disease course. Therefore, inhibition of enzymes that break down acetylcholine can be beneficial in the treatment of Alzheimer’s.
Cholinesterase inhibitors increase the levels of the neurotransmitter, Acetylcholine by inhibiting its breakdown. They are the initial drug of choice in all patients newly diagnosed with Alzheimer’s disease and can modestly improve symptoms. Common cholinesterase inhibitors used in the treatment of Alzheimer’s disease are galantamine, rivastigmine, and donepezil.

NMDA receptor antagonist

Memantine, an NMDA receptor antagonist is also used in the treatment of Alzheimer’s disease. It is specially used in those patients who cannot tolerate treatment with Cholinesterase inhibitors. There is moderate improvement in symptoms when treated with memantine. While combined treatment of memantine with other cholinesterase inhibitors has not been proven to be beneficial, studies are being conducted to observe any possible benefits.

Alternative medicine

Many vitamins, supplements, and herbs are also used in patients with Alzheimer’s disease as they may be beneficial for improving cognitive function. Studies that evaluate the benefits of these medications are still inconclusive. Some alternative treatments that may have beneficial effects are:

9-Me-BC Powder

9-ME-β-Carbolines are pyridoindole compounds, that are sourced from both endogenous and exogenous routes. Research on 9-ME-β-Carbolines has found that these compounds can exert beneficial effects such as neuroprotection, neurostimulation, anti-inflammatory action, and neuroregeneration. Furthermore, 9-ME-BC inhibited the proliferation of dopaminergic neurons without affecting dopamine uptake. 9-ME-BC displayed anti-proliferative actions with minimal toxic effects in the neurons.
9-ME-BC’s actions are mediated by the organic cation transporter, and also trigger the expression of genes responsible for the synthesis of many essential neurotrophic factors including BDNF, NCAM1, and TGFB2. These neurotrophic factors are essential for the outgrowth of neurites, which can have neurodegenerative and neuroprotective benefits when neurons are encountering various toxins. Hence, 9-ME-BC has many benefits on neurons which make it a beneficial supplement against neurological disorders such as Parkinson’s disease and Alzheimer’s disease.

CMS121 Powder

CMS121 derived from fisetin is a neuroprotective compound that is orally administered. Fisetin is a flavonoid compound derived from fruits and vegetables. Studies have shown that fisetin has beneficial effects on cognition and neuronal communication. Along with its antioxidant properties, fisetin can also enhance levels of neuroprotective factors within the Central Nervous System. Furthermore, fisetin also possesses anti-inflammatory properties. All of these benefits of fisetin indicate that it may be beneficial in the treatment of diseases that have disruptions in neuronal communication and functioning.
The derivative of fisetin, CMS121 powder has 400 times higher potency than fisetin. CMS121 also displayed additional properties such as improvement in pharmacological profile and stability in its physical form with good oral bioavailability. CMS121 can theoretically be a useful supplement in patients with neurological disorders such as Alzheimer’s disease.

CAD31 powder

CAD31 possesses multiple beneficial effects that may be effective in slowing down age-related degeneration of neurons. It has been shown to stimulate stem cells derived from human embryos to replicate. Experiments to test out the benefits of CAD31 in a clinical scenario were performed in animal studies. Mice models with Alzheimer’s disease were administered with CAD31. The study noted improvement in memory functions and a decrease in inflammation in mice models. It concluded that CAD31 can be neuroprotective and is also able to cross the blood-brain barrier effectively.
CAD 31 mainly acts via the formation of synapses and targets metabolic pathways such as the metabolism of fatty acids. These early studies have promising findings for the use of CAD-21 in neurological disorders including Alzheimer’s disease and other forms of senile dementia.

J147 powder

J147 powder is derived from Curcumin, which itself comes from a popular Indian spice known as turmeric. Curcumin is a compound with well-known beneficial effects such as anti-inflammatory properties, antioxidant effects, minimizing amyloid protein-induced toxicity, and so on. Unfortunately, curcumin itself was not an effective supplement as it has extremely poor bioavailability and cannot cross the blood-brain barrier either.
Unlike curcumin, J147 powder has a much more stable pharmacological profile, good CNS penetrance, and also has good oral bioavailability. J147 molecule also has over 10 times higher potency in comparison to curcumin. Animal studies conducted so far on J147 powder have shown that it may be highly beneficial in both the aging population and in those suffering from Alzheimer’s disease.

Monosialotetrahexosyl ganglioside Sodium (GM1) powder

Monosialotetrahexosylganglioside sodium (GM1) is an increasingly popular compound used to treat various neurological disorders. This is chiefly due to its neuroprotective action. But it also has beneficial protective actions on blood vessels supplying the CNS. In a study conducted on the GM1 compound, GM1 was found to have protective actions on free radicals induced cell injuries.
The neuroprotective, as well as the antioxidant properties of Monosialotetrahexosyl ganglioside Sodium (GM1) powder, make it a potentially beneficial supplement for many disorders of the central nervous system including but not limited to Alzheimer’s disease, Parkinson’s disease, senile dementia, and so on.

Octacosanol powder

Octacosanol is a chemical compound derived from plants such as wheat germ oil and sugar. Structurally and chemically, it has similar properties to Vitamin E. Several studies have found octacosanol to have antioxidant, neuroprotective, and anti-inflammatory properties. It is widely used by athletes and is also used as an adjunct in the treatment of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, Lou Gehrig’s disease, and many more.

Ongoing Studies On Alzheimer’s Disease

There is no cure for Alzheimer’s disease currently, and all drugs currently used in the treatment of Alzheimer’s disease can only improve the symptoms temporarily by enhancing the action of neurotransmitters within the central nervous system. But these drugs cannot prevent the disease from progressing.
Many studies are being conducted to better understand the underlying disease etiology and pathophysiology to develop targeted treatments for Alzheimer’s. Researchers in this field hope to find treatment options that can delay or even halt the disease progression to an advanced stage. It is likely that future treatment modalities will not involve a single drug, but a combination of several drugs acting on multiple pathways.

Prognosis of Alzheimer’s Disease

While several medications are used to treat Alzheimer’s disease, they can only slow down the disease progression. However, these medications are still very valuable as they improve the patient’s ability to be independent and perform their daily activities with minimal help. Various services are available that provide care for patients with Alzheimer’s disease. Unfortunately, there is no known cure for Alzheimer’s disease.

Reference:

1. Gruss M, Appenroth D, Flubacher A, Enzensperger C, Bock J, Fleck C, Gille G, Braun K. 9-Methyl-β-carboline-induced cognitive enhancement is associated with elevated hippocampal dopamine levels and dendritic and synaptic proliferation. J Neurochem. 2012 Jun;121(6):924-31.
2. Ates G, Goldberg J, Currais A, Maher P. CMS121, a fatty acid synthase inhibitor, protects against excess lipid peroxidation and inflammation and alleviates cognitive loss in a transgenic mouse model of Alzheimer's disease. Redox Biol. 2020 Sep;36:101648. doi: 10.1016/j.redox.2020.101648. Epub 2020 Jul 21. PMID: 32863221; PMCID: PMC7394765.
3. Daugherty D, Goldberg J, Fischer W, Dargusch R, Maher P, Schubert D. A novel Alzheimer's disease drug candidate targeting inflammation and fatty acid metabolism. Alzheimers Res Ther. 2017 Jul 14;9(1):50. doi: 10.1186/s13195-017-0277-3. PMID: 28709449; PMCID: PMC5513091.
4. Clarkson GJ, Farrán MÁ, Claramunt RM, Alkorta I, Elguero J. The structure of the anti-aging agent J147 used for treating Alzheimer's disease. Acta Crystallogr C Struct Chem. 2019 Mar 1;75(Pt 3):271-276.
5. Shi M, Zhu J, Deng H. Clinical Characteristics of Intravenous Injection of Monosialotetrahexosyl Ganglioside Sodium-Related Guillain-Barre Syndrome. Front Neurol. 2019 Mar 15;10:225.
6. Snider SR. Octacosanol in parkinsonism. Ann Neurol. 1984 Dec;16(6):723. doi: 10.1002/ana.410160615. PMID: 6395790.
7. Guo T, Lin Q, Li X, Nie Y, Wang L, Shi L, Xu W, Hu T, Guo T, Luo F. Octacosanol Attenuates Inflammation in Both RAW264.7 Macrophages and a Mouse Model of Colitis. J Agric Food Chem. 2017 May 10;65(18):3647-3658.
8. Alzheimer's Association. 2016 Alzheimer's disease facts and figures. Alzheimers Dement. 2016 Apr;12(4):459-509.
9. Mantzavinos V, Alexiou A. Biomarkers for Alzheimer's Disease Diagnosis. Curr Alzheimer Res. 2017;14(11):1149-1154. doi: 10.2174/1567205014666170203125942. PMID: 28164766; PMCID: PMC5684784.

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