Alzheimer’s Latest Facts: Causes, Pathophysiology, Symptoms, Diagnosis, Prevention, and Treatment

What is Alzheimer’s disease?

Alzheimer’s disease can be defined as a chronic neurodegenerative disease. It has been found to be the cause of around 60–70% of all cases of dementia. Most often Alzheimer’s disease begins in people aged over 65 years, although around 4–5% of cases develop earlier and are known as early-onset Alzheimer’s. The disease starts slowly and gradually worsens.

It roughly affects about 6% of the population aged 65 and older. In 2015, there were approximately 29.8 million cases of Alzheimer’s disease worldwide with dementia resulting in about 1.9 million deaths. In developed countries, Alzheimer’s disease is one of the most financially costly diseases due to the care required.

What causes Alzheimer’s disease?

The cause of Alzheimer’s disease is still poorly understood. Various risk factors are suspected with about 70% of the risk believed to be related to genetics and thereby inherited from the individual’s parents. Other possible causes include a history of hypertension, depression, and a history of head injuries. The definite cause for Alzheimer’s disease is still mostly unknown except for 1% to 5% of cases where genetic differences have been identified. There are several hypotheses that try to explain the cause of the disease, but none have yet to be proven.

Pathophysiology

Alzheimer’s disease is a neurodegenerative disease and is characterized by the loss of neurons and synapses in the cerebral cortex and other regions. This loss results in the gross atrophy of all the affected regions. This has been confirmed by imaging of the brain using MRI and PET scans, which have identified reductions in the size of specific regions of the brain, as patients progressed from mild cognitive impairment to Alzheimer’s disease.

What are the signs and symptoms of Alzheimer’s disease?

The disease course progresses through four stages, resulting in progressively worse cognitive and functional impairment.

1. Pre-dementia

This stage can be defined as the prodromal stage of Alzheimer’s disease as detailed neuropsychological testing has revealed mild cognitive difficulties up to eight years before a person fits the clinical criteria to be diagnosed with Alzheimer’s disease. However, the first symptoms are usually mistakenly attributed to aging or stress. This preclinical stage of the disease is also termed mild cognitive impairment (MCI). This is likely a transitional stage from normal aging to dementia. The early symptoms usually affect complex activities associated with daily living.

- Short-term memory is noticeably affected and can present as difficulty remembering recent information and an inability to acquire new knowledge. This may also be associated with reduced awareness of subtle memory difficulties. Not remembering exact details, forgetting things occasionally, misplacing items sometimes and minor short-term memory loss are attributed to aging and not due to Alzheimer’s disease.
- There may be problems with executive brain functions such as attentiveness, planning, and abstract thinking.
- Depressive symptoms, irritability can also be present.
- Apathy is also commonly observed at this stage, and it is the most persistent symptom throughout the stages of the disease.

2. Early

Worsening of features seen in the pre-dementia stage may eventually lead to a definitive diagnosis of Alzheimer’s disease. Although memory problems are prominent, in a small percentage of cases, difficulties with cognitive functions, language, perception, or execution of movements are more prominent than memory problems. Features that are seen in the early stages of Alzheimer’s disease are as follow:

- Increasing impairment of learning and memory. However, Alzheimer’s does not affect all types of memory equally. Older memories learned knowledge, and implicit memory (the memory of the body on how to do routine things) are affected less when compared to new facts or more recent memories.
- Language problems leading to a general deterioration in spoken and written language are mainly attributed to less vocabulary and decreased fluency. However, in this stage, the person with Alzheimer’s is usually capable of communicating basic ideas adequately.
- Difficulties performing fine motor tasks such as writing, drawing, or dressing and certain movement coordination may be present, but these features usually go unnoticed.
- As the disease progresses, people in this stage of Alzheimer’s are still able to perform many tasks independently but may need assistance or supervision with the most cognitively demanding activities.

3. Moderate

As the disease progresses behavioral and neuropsychiatric changes become more prominent. Progressive deterioration eventually hinders independence, with subjects being unable to perform the most common activities of daily living. In this stage:

- Memory problems worsen, and the person may fail to recognize close relatives. Furthermore, long-term memory, which was previously intact, becomes impaired.
- Speech difficulties become more evident due to the inability to recall vocabulary, which leads to frequent incorrect word substitutions (paraphasias).
- Reading and writing skills are progressively lost.
- Motor activities become less coordinated with an increased risk of falling as the disease progresses.
- Other common manifestations are wandering, irritability, and labile affect, leading to crying, and behavioral changes such as outbursts of aggression and resistance to caregiving.
- Approximately 30% of people with Alzheimer’s will develop delusional symptoms.
- Subjects will lose insight into their ongoing disease process and limitations.
- Urinary incontinence may develop

4. Advanced

By the time the disease has progressed to the final stages, the patient will be completely dependent upon caregivers. At this stage:

- Language is reduced to simple phrases or even single words and will eventually lead to complete loss of speech. However, despite the loss of language skills, people can often understand and return emotional signals.
- Aggressiveness may be present, but extreme apathy and exhaustion are much more common.
- People with Alzheimer’s disease will eventually not be able to perform even the simplest of tasks independently as strength and mobility deteriorate to the point where they are bedridden and unable to take care of themselves. The cause of death is usually an external factor, such as infection or pneumonia, and not the disease itself.

Diagnosis

Alzheimer’s disease is suspected based on the person’s medical history, history from relatives/caretakers, and behavior. Caregivers can provide important information on the daily activities, as well as the progressive decline of the person’s mental functions. A caregiver’s viewpoint is particularly important, as a person with Alzheimer’s disease is usually unaware of his own deficits.

Characteristic neurological and neuropsychological features along with the absence of an alternative explanation for those features are considered to be supportive of the diagnosis of Alzheimer’s disease. Assessment of intellectual functions including memory testing and evaluating cognitive impairment using the mini-mental state examination (MMSE) can be helpful in diagnosing and characterizing the state of the disease.

Supplemental tests such as blood tests can be used to identify other causes of dementia other than Alzheimer’s disease. The following should be assessed and ruled out:

Thyroid problems
Vitamin B12 deficiency
Syphilis
Metabolic problems (with tests for kidney function, liver function, electrolyte levels, and diabetes)
Heavy metals poisoning (e.g., lead, mercury)
Anemia

Imaging of the brain is useful to exclude other cerebral pathologies which can cause dementia. Imaging can also identify a reduction in the size of specific regions of the brain affected by Alzheimer’s thus confirming the diagnosis.

The diagnosis can be confirmed post-mortem if brain material is examined histologically.

In order to standardize the diagnostic process for Alzheimer’s disease, medical organizations have created diagnostic criteria.

Alzheimer’s Disease and Related Disorders Association (ADRDA, now known as the Alzheimer’s Association) and the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) established the most commonly used NINCDS-ADRDA Alzheimer’s Criteria in 1984 and updated it in 2007. According to these criteria, a person with cognitive impairment, along with suspected dementia, should undergo neuropsychological testing in order to clinically diagnose Alzheimer’s disease. Eight intellectual components commonly impaired in Alzheimer’s disease are:

Memory
Language
Perception
Attention
Motor skills
Orientation
Problem-solving
Executive functional abilities.

These domains are the ones tested in the NINCDS-ADRDA Alzheimer’s Criteria as listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) published by the American Psychiatric Association.

Prevention

Currently, there is no definitive evidence to support measures that are effective in preventing Alzheimer’s disease. Studies have suspected relationships between certain modifiable factors, such as diet, cardiovascular disease, and lifestyle among others, and the likelihood of developing the disease. Only further research will reveal whether these factors can truly help prevent Alzheimer’s.

Diet – People who maintain a healthy diet are likely to have a reduced risk of developing Alzheimer’s disease while those who eat a diet high in saturated fats and simple carbohydrates may have a higher risk. There is limited evidence that suggests mild to moderate use of alcohol, particularly red wine, is associated with a lower risk. There is also tentative evidence that caffeine may be protective. Moreover, there is evidence that some foods such as cocoa, red wine, and tea may decrease the risk of AD. However, these results differ between different populations and are therefore not conclusive.
Cardiovascular disease risk – Cardiovascular disease risk factors, such as hypercholesterolemia, hypertension, diabetes, and smoking, are associated with a higher risk of Alzheimer’s.
Lifestyle – People who engage in intellectual activities such as reading, playing board games, playing musical instruments, and engage in regular social interactions have shown a reduced risk of developing Alzheimer’s disease. It is believed that education may delay the onset of disease as well. Physical activity is also associated with a reduced risk of Alzheimer’s disease as well as a decreased occurrence of dementia.

Treatment

There is no definitive medical cure for Alzheimer’s disease. Current treatment options can be divided into pharmaceutical, psychosocial, and caregiving.

Medications – No medication can delay or halt the progression of the disease. Current treatment regimens only offer a relatively small symptomatic benefit by temporarily improving symptoms.

Psychosocial – Psychosocial interventions are used alongside medications to improve the quality of life of people suffering from Alzheimer’s disease. However, research on the efficacy of these treatments is are not conclusive and they are used to support dementia patients in general.

- Behavioral interventions can help to reduce some specific problem behaviors, such as incontinence.
- Emotion-oriented interventions may help impaired people adjust to their illness.
- Cognition-oriented treatments may be useful in the reduction of cognitive deficits.
- Stimulation-oriented treatments which include art, music, exercise, and other recreational activities may improve behavior and mood.

Caregiving – Since Alzheimer’s disease has no definitive cure and the disease renders people incapable of taking care of themselves, caregiving essentially becomes the main mode of treatment.

- During the early stages of the disease, modifications to the environment and lifestyle such as simplified daily routines, placing of safety locks, should be done for the safety of the patient and to reduce the burden on the caretaker.
- If eating becomes difficult, food should be prepared in smaller pieces or even pureed. If swallowing difficulties arise, feeding tubes may be required.
- As the disease progresses, different medical complications can arise, such as pressure ulcers, malnutrition, respiratory, skin, or eye infections. While careful management can prevent them, professional treatment is needed if they do arise.
- During the final stages of the disease, care is focused on relieving discomfort until death.

Prognosis

The life expectancy of people with Alzheimer’s disease is reduced. Men have a less favorable survival prognosis when compared to women. After the diagnosis, life expectancy ranges from three to ten years and fewer than 3% of people live for more than fourteen years. If diagnosed at an earlier age the total survival years can be higher but when compared to the healthy population life expectancy is significantly reduced. Pneumonia and dehydration are the most common causes of death due to Alzheimer’s disease.

My opinion

Alzheimer’s disease, a chronic neurodegenerative disease with no definite cause, is difficult to diagnose early as initial symptoms are often mistaken for normal aging. Usually, a definitive diagnosis is only made once cognitive impairment starts compromising daily activities. The symptoms will then progress from mild cognitive problems, such as memory loss, to progressively worse problems such as poor motor coordination and the inability to speak, finally eliminating the ability of the person to live independently. As there are no treatments to stop or reverse the progression of the disease, affected people rely on others for assistance often placing a burden on the caregiver. These burdens may be social, physical, psychological, and economic. Therefore, extensive research is required to identify a possible cause and to find a definitive medical cure to reduce the burden caused by Alzheimer’s disease.

References

1. Burns A, Iliffe S (February 2009). “Alzheimer’s disease”. BMJ. 338: b158

2. “Dementia Fact sheet”. World Health Organization. 12 December 2017.

3. “Dementia diagnosis and assessment” (PDF). National Institute for Health and Care Excellence (NICE).

4. Förstl H, Kurz A (1999). “Clinical features of Alzheimer’s disease”. European Archives of Psychiatry and Clinical Neuroscience. 249 (6): 288–90.

5. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (July 1984). “Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease”. Neurology. 34 (7): 939–44.

6. Rabins PV, Blacker D, Rovner BW, Rummans T, Schneider LS, Tariot PN, et al. (Steering Committee on Practice Guidelines) (December 2007). “American Psychiatric Association practice guideline for the treatment of patients with Alzheimer’s disease and other dementias. Second edition”. The American Journal of Psychiatry. 164 (12 Suppl): 5–56.

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