All About Alzheimer’s: Symptoms, Causes & Pathophysiology Simplified

what is alzheimers

Alzheimer’s disease and dementia , though related, are not the same. Alzheimer’s is a type of dementia.

DSM-V has recently changed the term ‘dementia’ with ‘major neurocognitive disorder’ to remove the stigma attached with the ailment.

Dementia is a group of symptoms that are marked by memory loss, the decline in cognitive function, language disturbances as well as behavioral changes.

It marks a rapid decline in an individual’s baseline intellectual and cognitive function to the extent that it can interfere in his day to day life. The common causes of dementia include Alzheimer’s disease, stroke, Lewy body formation, frontotemporal dementia.

Other factors may also contribute to dementia as a symptom rather than a disorder such as a thyroid dysfunction, vitamin B12 deficiency etc.

Alzheimer’s disease is a type of dementia and this post will help you understand symptoms, causes and available treatment for Alzheimer’s.

What Is Alzheimer’s Disease?

Alzheimer’s disease is the most common form of dementia. It is a neurodegenerative disorder wherein both brain function and structure deteriorates.

Alzheimer’s disease is named after the German psychiatrist Alois Alzheimer who first described this disorder a century ago. In 1906, he reported a case of peculiar dementia in a 51-year-old woman.

After her death at 55 years of age, he conducted tests to investigate the link between the alteration in her cognitive and behavioral skills and development of structural changes in her brain.

The preliminary aspect of the disease is abnormal protein aggregation and accumulation in the brain.

Two major proteins involved are amyloid beta and tau. Amyloid plaques and neurofibrillary tangles are the two forms of protein accumulation in Alzheimer’s disease.

And the most important symptom of Alzheimer’s disease is impaired memory.

How Common Are Alzheimer’s Disease And Dementia?

More than 25 million people over the world have dementia and most of them suffer from Alzheimer’s. Around 5 million new cases are reported every year.

About 9.7% of the population above 70 years in the US is diagnosed with Alzheimer’s. In UK, the prevalence rate for dementia is 6.4% and for Alzheimer’s it is 4.4% in a population above the age of 65 years.

The global prevalence rate of dementia is 3.9% in individuals above 60 years of age. In developed nations, 1 in 10 of elderly individuals is affected by the certain degree of dementia. And the rates of dementia are expected to double every 20 years.

The number of persons with Alzheimer’s disease in the US population in 2000 was estimated to be 4.5 million, and by 2050 this number was projected to increase by almost threefold, to 13.2 million.

In 2006 the worldwide total number of patients with AD was 26.6 million, and by 2050 the number will quadruple.

What Are The Stages Of Alzheimer’s Disease?

The National Institute on Aging / Alzheimer’s Association presents three major classifications of Alzheimer’s disease:

  • Preclinical Alzheimer’s
  • Mild cognitive impairment caused by Alzheimer’s
  • Dementia caused by Alzheimer’s

Regarding disease stages the classification of Alzheimer’s include:

  • Early stage Alzheimer’s disease
  • Moderate to severe Alzheimer’s
  • Severe Alzheimer’s

Other terms that are used about Alzheimer’s include:

Preclinical Alzheimer’s disease is when patients may present with changes in the brain tissue but not present with overt symptoms of dementia.

Dementia of Alzheimer’s type is the presenile form as indicated by Alois Alzheimer.

Senile dementia of Alzheimer’s type may include individuals presenting with senility and hardening of arteries.

Late onset Alzheimer’s (LOAD) is developing signs and symptoms of Alzheimer’s at a late age of 65 and above.

Early-onset Alzheimer’s disease is developing symptoms before the age of 55, 60 or 65 years.

Familial Alzheimer’s disease is those who have Alzheimer’s and have a family history of Alzheimer’s as well.

What Are The Symptoms Of Alzheimer’s?

The symptoms of early stage Alzheimer’s disease include:

  • Forgetfulness or Impaired recent memory (unable to recognize common things, unable to retain recently acquired knowledge)
  • Difficulty in concentrating
  • Alterations in problem-solving skills
  • Inability to judge
  • Disorientation
  • Language dysfunction
  • Problems in vision
  • Impaired sense of smell
  • Depression
  • Withdrawal from family and friends

These are signs of the early stage of Alzheimer’s wherein family and friends realize that individual has a reduction in his baseline behavior and cognition but the individual maintains other activity in the society such as driving and thus the individual appears normal.

Early stage Alzheimer’s dementia may last for 2-5 years. 50% of the individuals with Alzheimer’s are unaware of their illness and remain in psychological denial.

In early Alzheimer’s individuals may have difficulty in handling money, may repeat questions, may misplace objects and take longer than usual to complete tasks.

In the moderate stage, there is an increased impairment in memory as well as inability to be independent in social activities. Basic routine activities may also require assistance or supervision.

Agitation, psychosis, anxiety, and depression may be more pronounced at this stage. The newly learned material is rapidly lost or retained in fragments.

Disorientation may occur, and individuals may stop recognizing family members and friends. Aggression, wandering, hallucinations, irritability may occur.

In severe Alzheimer’s, patients are dependent caregivers for day to day activity and in later stages may also become mute, not able to control bladder and bowel function and also not be able to move.

What Causes Alzheimer’s Disease?

Scientists have identified various causative factors for Alzheimer’s disease, few of which we will go through:

1.Aging may predispose one to Alzheimer’s (depending on other factors)

As per the theory of aging, it is said that changes occurring in the brain in Alzheimer’s disease are similar to those occurring as consequence of natural aging, but they differ on the grounds of the severity of the symptoms.

Studies indicate that pathological tests can’t identify the difference between changes in brain tissue in normal aging and early stage Alzheimer’s disease.

Formation of senile plaques is common in individuals above the age of 55 years, and this could be the reason for transition from early stage Alzheimer’s disease to advanced Alzheimer’s disease.

It has been observed that beta amyloid deposits are common in individuals above 66 years of age even if they are not experiencing dementia.

Similarly, the other protein form that accumulates -neurofibrillary tangles are found to be a causative factor for memory loss not only in Alzheimer’s disease but also in normal aging.

Age-related degeneration in myelin sheath ( tissue that covers and protects neurons or nerve cells) and destruction of neurons could result also in the development of Alzheimer’s disease.

2.Environmental factors may contribute to Alzheimer’s development

A clear link between aluminum and Alzheimer’s development has not been established. Certain studies have found a slight link between exposure to aluminium-containing products and risk of developing Alzheimer’s disease.

Landsberg et.al have demonstrated that aluminum is absent in the plaques seen in Alzheimer’s disease.

Recent studies suggest that aluminum may be responsible for disease progression of Alzheimer’s and there may be a plausible genetic link.

Reducing exposure to aluminum is thought to be a strategy to prevent Alzheimer’s disease.

Some studies point that head injury could increase the risk of developing Alzheimer’s due to the state of inflammation and immune dysregulation triggered by this condition.

Abalan was the first to describe the link between Alzheimer’s disease and diet.

Sparks et.al demonstrated that high dietary cholesterol could induce beta-amyloid accumulation.

Initially it was observed that prevalence rates of Alzheimer’s disease were lower in smokers than non-smokers; however, this was probably because it did not take into account survival rates.

However, follow up studies found that smoking increases the risk of Alzheimer’s.

A study demonstrates that mid age heavy drinkers are at three times the risk of developing Alzheimer’s and dementia in late life than non-drinkers.

Interestingly light or moderate alcohol consumption reduces the risk of dementia and Alzheimer’s.

3.Genetic predisposition and hereditary links increase risk of Alzheimer’s

Mutations in 3 genes: Amyloid precursor protein, presenilin-1, and presenilin-2 genes contribute to 2-5% of the Alzheimer’s cases.

First degree relative of Alzheimer’s patients is at a higher risk of developing Alzheimer’s at any point of time than the general populace.

Apolipoprotein ε4 allele is identified as a susceptibility gene for Alzheimer’s disease. With the increase in expression of this gene, the risk of developing Alzheimer’s disease increases and the age of onset decreases.

Other genes like angiotensin-I converting enzyme, cholesterol 24-hydroxylase, and insulin-degrading enzyme genes have also been linked with the development of vascular Alzheimer’s disease.

4.Inflammation contributes to Alzheimer’s progression

Review studies indicate that use of NSAIDs or non-steroidal anti-inflammatory drugs have a protective effect in Alzheimer’s.

High levels of C-reactive protein (an inflammatory marker) at midlife increases the risk of developing any form of dementia by three folds.

Follow-up studies also indicate the positive link between increased risk of dementia and Alzheimer’s with increased circulating inflammatory markers.

5.Immune system dysfunction is observed in Alzheimer’s

Various studies have identified the possible role of immune system dysfunction in the development of Alzheimer’s disease.

Researchers believe that initially the immune system is activated to mitigate the structural abnormalities in Alzheimer’s.

But after remaining active for a prolonged period the immune system may cause slow damage to the neurons and eventually lead to cell death.

Two main features of abnormal function of immune system observed in Alzheimer’s include: Attachment of complement proteins ( a type of immune conferring agents) to diseased tissue as well as prolonged activation of various immune cells in the brain.

Armstrong et.al suggest a hypothesis that heavy metal toxicity could cause an immune system dysfunction in Alzheimer’s.

Perturbation of immune function by infectious agents is also found to contribute to amyloid beta accumulation.

6.Metabolic health disruptions increase risk of developing Alzheimer’s

Various studies have investigated the role of BMI or body mass index in the development of Alzheimer’s.

A review study indicates that higher BMI during midlife is a risk factor for the development of Alzheimer’s disease; however rapid decline in body weight during late life may mark the onset of dementia.

Elevated blood pressure and cholesterol levels during midlife have been linked with increased risk of developing Alzheimer’s disease in late life.

Midlife diabetes has also been linked with the development of dementia and Alzheimer’s.

Cardiovascular diseases , like heart failure, atherosclerosis, and even stroke, increase the risk of dementia and Alzheimer’s.

Alzheimer’s Pathophysiology: Explained

When it comes to the level of what happens in the brain tissue, the three main features include :

  • Accumulation of amyloid beta plaque
  • Formation of neurofibrillary tangles
  • Loss of neurons

Amyloid beta protein is derived from a larger protein, amyloid precursor protein and these deposited the brain. These proteins get aggregated in an insoluble form known as ‘diffuse’ plaques.

These plaques are surrounded by degenerating neurites (axons and dendrites which are parts of the brain cells) This triggers inflammation and activation of various immune cells in the brain.

When these amyloid beta plaques get deposited in blood vessels, they are called cerebrovascular plaques or cerebral amyloid angiopathy.

Neurofibrillary tangles originate from aggregated form of a protein known as tau. Normally tau serves as part of structural proteins in brain cells, but in Alzheimer’s it undergoes certain changes which cause it to accumulate separately as neurofibrillary tangles.

These impair the function of normal neurons and lead to progression of the disease. The aggregation of these proteins initiate cognitive decline and worsen Alzheimer’s disease.

Apart from the development of plaques and tangles, synapses (connection between two brain cells) are lost, cell death in neurons occurs.

And there is an imbalance in certain neurotransmitters (chemicals in the brain for communication of cells).

Specifically, a loss in ‘cholinergic’ neurons is observed; these utilize the neurotransmitter acetylcholinesterase and are involved in memory and attention.

Various networks between brain regions and limbic system are also impaired in Alzheimer’s. Disruptions in these networks can affect internally directed behaviors and goal-directed tasks.

Once formed these plaques of amyloid beta and tau spread from cell to cell thereby impacting various regions of the brain and impairing more than just memory.

Can Alzheimer’s Be Prevented?

Yes, the onset of dementia can be delayed by changing lifestyle and dietary factors, whereas medications and proper care may help in improving the quality of life and cognition in early stage Alzheimer’s and dementia.

One of the main strategies that one can implement is to ensure that you have a good vascular and metabolic health.

Mitigating mid-life hypertension, obesity, and metabolic syndrome is often possible with good diet and physical activity. This in turn cuts down a significant proportion of risk factors for Alzheimer’s.

Another important aspect is to engage in intellectually stimulating activities and lifestyles that are more active and socially more interactive. Mental well-being can also reduce the risk of Alzheimer’s.

What Is The Treatment For Alzheimer’s?

The prime strategy of treatment for Alzheimer’s treatment involves reduction of plaques.

Medications as therapy for Alzheimer’s

This includes the following:

  • Drugs interfering with amyloid beta aggregation
    These include anti-amyloid aggregation agents, selective Aβ42-lowering agents, and immunotherapy, each of which works towards reducing amyloid beta plaque deposition.
  • Drugs interfering with tau deposition
    These include tau aggregation inhibitors, agents that prevent tau phosphorylation (a process by which tau aggregates are formed) and immunotherapy.

Other diseases modifying treatment approaches include the use of anti-inflammatory drugs, antioxidants and cholesterol-lowering agents that target aspects that could contribute to the progression of the disease.

As part of other treatment goals, cholinesterase inhibitors are used to attenuate memory loss and other neuropsychiatric symptoms.

Three medications used as first line of treatment in Alzheimer’s include: donepezil, rivastigmine, and galantamine.

Memantine is another drug that is used in Alzheimer’s treatment and aids in improving cognition and behavioral symptoms.

Other medications like antidepressants, antipsychotics, SSRIs are also used to manage behavioral and psychiatric symptoms in Alzheimer’s.

Therapy other than medicines for Alzheimer’s

Non-pharmacological methods of treatment can be used to treat behavioral symptoms such as:

  • ABC’s: Look for Antecedent of Behaviours and Consequences
  • 3 R’s: Repeat Reassure and Redirect
  • Minimize wandering
  • Caregiver Empowerment

Conclusion

1 in 10 individuals of 65 years of age or older has Alzheimer’s dementia. Over 24 million cases of dementia have been reported worldwide.

Around 5.5 million Americans live with Alzheimer’s disease in 2017. $259 billion is the estimated expense of treatment of Alzheimer’s and other dementia types in the US.

These figures are a rough estimate but also a strong indicator to search for prevention strategies for Alzheimer’s.

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