Alzheimer's disease

Alzheimer's disease develops as a result of progressive loss of cognitive abilities and is characterized by the formation of senile plaques, accumulation of amyloid and neurofibrillary glomeruli in the cerebral cortex and subcortical gray matter. Current medications can temporarily stop the progression of Alzheimer's symptoms, but the disease cannot be completely cured.

[1], [2],

Epidemiology

It is a neurological disease that is the most common cause of Dementia is more than 65% of dementia in the elderly. It is twice as common in women than in men, which is partly due to the longer life expectancy for women. Alzheimer's disease affects about 4% of people aged 65 to 74 years and more than 30% - over the age of 85 years. The predominance of the number of patients in developed countries is associated with an increase in the number of elderly people.

[3], [4], [5], [6], [7], [8], [9], [10],

Causes of the alzheimer's disease

Most cases of the disease are sporadic, with a late onset (older than 60 years) and an unclear etiology. However, from 5 to 15% is familial in nature, half of these cases have an earlier onset (younger than 60 years) and are usually associated with specific genetic mutations.

Typical morphological changes are extracellular  accumulation of a-amyloid, intracellular neurofibrillary glomeruli (paired helix-shaped filaments), the development of senile plaques and the loss of neurons. Usually,  cortical atrophy, a decrease in glucose consumption, and a decrease in cerebral perfusion in the parietal lobe, temporal cortex, and prefrontal cortex take place.

At least 5 specific genetic loci located on the 1st, 12th, 14th, 19th and 21st chromosome affect the occurrence and progression of Alzheimer's disease. The development of the disease involves genes encoding the processing of the precursor protein presenin I and presenilin II. Mutations in these genes can alter the processing of the amyloid precursor protein, leading to the accumulation of a-amyloid fibrillar aggregates. A-Amyloid can contribute to neuronal death and the formation of neurofibrillary glomeruli and senile plaques, which consist of degeneratively modified axons and dendrites, astrocytes and glial cells located around the amyloid nucleus.

Other genetic determinants include the apolipoprotein E (apo E) alleles. Apolipoprotein E affects the accumulation of β-amyloid, the integrity of the cytoskeleton and the efficiency of neuronal repair. The risk of Alzheimer's disease is greatly increased in people with two 4 alleles, and decreases in those who have 2 alleles.

Other common abnormalities include an increase in the concentration in the CSF and brain of the taurine protein (a component of neurofibrillary tangles and α-amyloid) and a decrease in the level of choline acetyltransferase and various neurotransmitters (in particular, somatostatin).

The relationship of environmental factors (exogenous) (including low hormone levels, susceptibility to metals) and Alzheimer's disease is under study, but no relationship has yet been confirmed.

[11], [12]

Risk factors

Scientists believe that Alzheimer's disease is caused by a combination of genetic and environmental factors as well as lifestyles that affect the brain throughout life.

[13]

Age

Age is the most important risk factor for Alzheimer's disease. The pace of development of dementia doubles every decade after 60 years.

[14], [15], [16]

Heredity

The risk of developing the disease is higher if a relative of the first relationship (parents or brother) has a history of dementia. However, only in 5% of cases the pathology is caused by genetic changes.

Most of the genetic mechanisms for the development of the disease remain unexplained.

[17]

Down syndrome

Many people with Down syndrome develop Alzheimer's disease. Signs and symptoms of the disease usually appear 10 to 20 years earlier.

Floor

Women often develop Alzheimer's disease, probably because they live longer than men.

[18]

Head injuries

People who have had serious head injuries in the past have a greater risk of developing Alzheimer's disease.

[19], [20], [21], [22], [23],

Lifestyle

Some research scientists suggest that the same risk factors that increase the chances of developing cardiovascular pathologies may also increase the likelihood of developing Alzheimer's disease. For example:

• Hypodynamia.
• Obesity.
• Smoking or passive smoking.
• Arterial hypertension.
• Hypercholesterolemia and triglyceridemia.
• Type 2 diabetes.
• Food with insufficient amount of fruits and vegetables.

[24], [25], [26]

Symptoms of the alzheimer's disease

Symptoms and signs of Alzheimer's disease are similar to those of other types of dementia with early, intermediate and late stages of the disease. Loss of short-term memory is often the first symptom. The disease progresses steadily, but it may also have a plateau at some time intervals. Behavioral disorders are common (including vagrancy, irritability, shrillness).

[27], [28], [29]

Diagnostics of the alzheimer's disease

A neurologist performs a physical examination and a neurological examination to check the patient’s general neurological health, while checking:

• Reflexes.
• Muscle tone and strength.
• Sight and hearing.
• Coordination of movements.
• Equilibrium.

Typically, the diagnosis is similar to that for other types of dementia. Traditionally, diagnostic criteria for Alzheimer's disease include confirming dementia through physical examination and documenting the results of a formalized study of mental status; deficiency found in 2 or more cognitive areas, gradual onset and progressive deterioration of memory and other cognitive functions; lack of disturbance of consciousness; start after 40 years; most often after 65 years; lack of systemic diseases and diseases of the brain, which can be regarded as the cause of the progressive loss of memory and cognitive functions. Nevertheless, certain deviations from the listed criteria do not exclude the diagnosis of Alzheimer's disease.

Difference of Alzheimer's disease from other types of dementia presents certain difficulties. A set of assessment tests (for example, the Hachinsky Ischemic Scale) can help distinguish vascular dementia. Fluctuations in cognitive function, symptoms of parkinsonism, well-formed visual hallucinations and relative preservation of short-term memory are more likely to confirm the diagnosis of Taurus and Levy's Taurus, rather than Alzheimer's disease.

Patients with Alzheimer's disease, unlike other dementias, more often look more well-groomed and tidy. Approximately 85% of patients carefully collected history and neurological examination allow to confirm the correctness of the diagnosis.

Modified ischemic scale Khachinsky

Signs of	Points
Sudden onset of symptoms	2
Gradual increase of symptoms (disorders) (for example, deterioration - stabilization - deterioration)
Fluctuation (fluctuation) of symptoms	2
Normal orientation	One
Individual personality traits are relatively preserved.
Depression	One
Somatic complaints (such as tingling and awkwardness in the hands)
Emotional lability	One
Arterial hypertension now or in history
History of stroke	2
Confirmation of the presence of atherosclerosis (for example, pathology of peripheral arteries, myocardial infarction)
Focal neurological symptoms (eg, hemiparesis, homonymous hemianopsia, aphasia)
Focal neurological signs (for example, unilateral weakness, loss of sensitivity, asymmetry of reflexes, Babinsky symptom)

Total points: 4 suggests the initial stage of dementia; 4-7 - intermediate stage; 7 involves vascular dementia.

[30], [31], [32], [33]

Laboratory tests

Blood tests can help identify other potential causes of memory loss and attention, such as thyroid disease or vitamin deficiencies.

[34]

Brain research

Brain research is currently used to accurately identify visible pathological changes associated with other pathologies, such as stroke, trauma, or malignant or benign tumors that can lead to cognitive impairment.

• MRT.
• CT scan.
• Positron emission tomography. New methods of PET help to diagnose the degree of brain damage by amyloid plaques.
• Analysis of the liquor. An analysis of the cerebrospinal fluid can help identify biomarkers that indicate the likelihood of developing Alzheimer's disease.

New diagnostic tests

Scientists are constantly working with neurologists to develop new diagnostic tools that would help accurately diagnose Alzheimer's disease. Another important task is to identify the disease before the first symptoms appear.

New diagnostic tools that are in development:

• Development of new accurate brain imaging methods
• Accurate Mental Diagnostic Tests
• Determination of biomarkers of disease in the blood or cerebrospinal fluid.

Genetic testing is usually not recommended for the routine diagnosis of Alzheimer's disease. The exception is people who are burdened with family history.

[35], [36], [37], [38], [39],

Differential diagnosis

Differential diagnosis between Alzheimer's disease and Levi's dementia 

Sign of	Alzheimer's disease	Dementia with Levi's calves
Pathomorphology	Senile plaques, neurofibrillary glomeruli, accumulation of beta-amyloid in the cortex and subcortical gray matter	Levi's Taurus in Cortical Neurons
Epidemiology	Twice more often affects women	Twice more often affects men
Heredity	Family inheritance can be traced in 5-15% of cases	Rarely observed
Fluctuations during the day	To some extent	Clearly defined
Short term memory	Lost in the early stages of the disease	Suffer to a lesser extent; deficiency is more concerned with attention than memory
Symptoms of parkinsonism	Very rarely, they develop in the late stages of the disease, the gait is not disturbed.	Clearly expressed, usually occur in the early stages of the disease, there is axial rigidity and unstable gait
Dysfunction of the autonomic nervous system	Seldom	Usually available
Hallucinations	Approximately 20% of patients usually develop in the stage of moderate dementia.	It occurs in approximately 80% of patients, usually in the onset of the disease, most often visual
Adverse reactions to antipsychotics	Frequent, may aggravate the symptoms of dementia	Frequent, sharply worsen extrapyramidal symptoms and may be severe or life threatening

[40], [41], [42], [43], [44]

Treatment of the alzheimer's disease

The basic treatment for Alzheimer's disease is the same as for other types of dementia.

Cholinesterase inhibitors moderately improve cognitive function and memory in some patients. Four of them are approved for use: in general, donepezil, rivastigmine and galantamine are equally effective, but noacrine is used less frequently because it has hepatotoxicity. Donepezil is the drug of choice 1, since the daily dose is taken once and the drug is well tolerated by patients. The recommended dose is 5 mg once daily for 4-6 weeks, then the dose is increased to 10 mg / day. Treatment should be continued if after a few months from the beginning of the reception a functional improvement has appeared, otherwise it should be stopped. The greatest number of side effects noted from the gastrointestinal tract (including nausea, diarrhea). Rarely, dizziness and heart rhythm disturbances occur. Side effects can be minimized by gradually increasing the dose.

The recently approved N-methyl-O-aspartate receptor antagonist memantine (5–10 mg orally per dose) showed a slowdown in the progression of Alzheimer's disease.

Sometimes antidepressants are used in treatment to help control behavioral symptoms.

[45], [46], [47], [48], [49]

Creating a safe and supportive environment

Follow these simple guidelines to preserve the functional abilities of an Alzheimer's patient:

• Always keep your keys, wallets, mobile phones and other valuables in the same place.
• Install location tracking on your mobile phone.
• Use the calendar or whiteboard in the apartment to keep track of your daily schedule of household chores. Make it a habit to mark items already completed.
• Remove excess furniture, maintain order.
• Reduce the number of mirrors. People with Alzheimer's can sometimes not recognize themselves in the mirror image, which can frighten him.
• Keep in sight the photos with your relatives.

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Sport

Regular exercise is an important part of a wellness plan. Daily walks in the fresh air will help improve mood and preserve the health of joints, muscles and heart. Exercise can also improve sleep and prevent constipation.

[51], [52], [53]

Nutrition

People with Alzheimer's can sometimes forget to eat and drink enough water, which can lead to dehydration, constipation and exhaustion.

Nutritionists suggest eating the following foods:

• Cocktails and smoothies. You can add protein in powder form to the milkshake (you can buy it in some pharmacies).
• Water, natural juices and other healthy drinks. Ensure that a person with Alzheimer's disease drinks several glasses of water a day. Avoid caffeinated beverages. They can cause anxiety, insomnia, and frequent urination.

[54], [55], [56], [57]

Alternative medicine

Various herbal preparations, vitamin supplements and other dietary supplements are widely promoted as drugs that can improve cognitive functions,

Pharmaceutical companies offer several dietary supplements that can improve the cognitive abilities of a person suffering from this disease:

• Omega-3 fatty acids. They are found in large quantities in fish. Studies have not shown any benefit from dietary supplements containing fish oil.
• Curcumin. This herb has anti-inflammatory and antioxidant properties that can improve chemical processes in the brain. So far, clinical trials have not found any benefit in relation to Alzheimer's disease.
• Ginkgo Ginkgo - plant extract. A large study funded by the NIH found no effect in preventing or slowing the development of symptoms of Alzheimer's disease.
• Vitamin E. Although vitamin E cannot prevent the disease, however, taking 2000 IU per day can slow its progression in people who are already sick.

Estrogen therapy has shown no benefit in preventive treatment and may be unsafe.

[58]

Forecast

Although the rate of disease progression varies, cognitive decline is inevitable. The median survival time for diagnosis of Alzheimer's disease is 7 years, although this figure is debated.

[59], [60], [61], [62]