Alzheimer's disease

Alzheimer's disease is a progressive loss of cognitive abilities and is characterized by the formation of senile plaques, amyloid, and neurofibrillary tangles in the cerebral cortex and subcortical gray matter. Modern drugs can temporarily stop the progression of Alzheimer's symptoms, but there is no cure for the disease.

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Epidemiology

This neurological disorder is the most common cause of dementia, accounting for more than 65% of dementia in older people. It is twice as common in women as in men, partly due to women's longer life expectancy. Alzheimer's disease affects about 4% of people aged 65 to 74 years and more than 30% of people over 85 years. The prevalence of patients in developed countries is due to the increase in the number of elderly people there.

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Causes Alzheimer's disease

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

Typical morphological changes include extracellular accumulation of alpha-amyloid, intracellular neurofibrillary tangles (paired helical filaments), development of senile plaques, and neuronal loss.Cortical atrophy, decreased glucose uptake, and decreased cerebral perfusion in the parietal lobe, temporal cortex, and prefrontal cortex are common.

At least five distinct genetic loci located on chromosomes 1, 12, 14, 19, and 21 influence the onset and progression of Alzheimer's disease. Genes encoding the processing of presenilin I and presenilin II precursor protein are involved in the development of the disease. Mutations in these genes can alter the processing of amyloid precursor protein, leading to the accumulation of fibrillar aggregates of alpha-amyloid. Alpha-amyloid can contribute to the death of neurons and the formation of neurofibrillary tangles and senile plaques, which consist of degeneratively altered axons and dendrites, astrocytes, and glial cells located around the amyloid core.

Other genetic determinants include apolipoprotein E (apo E) alleles. Apo E influences β-amyloid accumulation, cytoskeletal integrity, and the efficiency of neuronal repair. The risk of Alzheimer's disease is significantly increased in people with two 4 alleles and decreased in those with two alleles.

Other common abnormalities include increased levels of the protein taurine (a component of neurofibrillary tangles and alpha-amyloid) in the CSF and brain and decreased levels of choline acetyltransferase and various neurotransmitters (particularly somatostatin).

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

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Risk factors

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

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Age

Age is the single biggest risk factor for Alzheimer's disease. The rate of dementia doubles every decade after age 60.

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Heredity

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

Most of the genetic mechanisms of disease development remain unexplained.

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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 are more likely to develop Alzheimer's disease, probably because they live longer than men.

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Head injuries

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

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Lifestyle

Some research suggests that the same risk factors that increase your chances of developing cardiovascular disease may also increase your chances of developing Alzheimer's disease. For example:

• Hypodynamia.
• Obesity.
• Smoking or passive smoking.
• Arterial hypertension.
• Hypercholesterolemia and triglyceridemia.
• Diabetes mellitus type 2.
• A diet that lacks fruits and vegetables.

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Symptoms Alzheimer's disease

The 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. Short-term memory loss is often the first symptom. The disease progresses steadily, but may also plateau at certain time intervals. Behavioral disturbances (including wandering, irritability, and screaming) are common.

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Diagnostics Alzheimer's disease

A neurologist performs a physical examination and neurological examination to check the patient's overall neurological health, checking for:

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

Diagnosis is generally similar to that for other types of dementia. Traditional diagnostic criteria for Alzheimer's disease include confirmation of dementia by physical examination and documentation of the results of a formal mental status examination; deficits in 2 or more cognitive areas, gradual onset and progressive deterioration of memory and other cognitive functions; no disturbances of consciousness; onset after age 40; most often after age 65; and no systemic or brain diseases that could be considered as the cause of the progressive decline in memory and cognitive functions. However, certain deviations from these criteria do not exclude a diagnosis of Alzheimer's disease.

Distinguishing Alzheimer's disease from other types of dementia is difficult. A battery of assessment tests (eg, the Hachinski Ischemic Scale) can help differentiate vascular dementia. Fluctuations in cognitive function, parkinsonian symptoms, well-defined visual hallucinations, and relative preservation of short-term memory support a diagnosis of dementia with Lewy bodies rather than Alzheimer's disease.

Patients with Alzheimer's disease, unlike other dementias, often look better groomed and tidy. In approximately 85% of patients, a carefully collected anamnesis and neurological examination can confirm the correct diagnosis.

Modified Khachinsky ischemic scale

Signs	Points
Sudden onset of symptoms	2
Stepwise increase in symptoms (disorders) (for example, worsening - stabilization - worsening)
Fluctuation of symptoms	2
Normal orientation	1
Individual personality traits are relatively preserved
Depression	1
Somatic complaints (eg, tingling and clumsiness in the hands)
Emotional lability	1
Current or history of arterial hypertension
History of stroke	2
Confirmation of the presence of atherosclerosis (eg, peripheral arterial disease, myocardial infarction)
Focal neurological symptoms (eg, hemiparesis, homonymous hemianopsia, aphasia)
Focal neurological signs (eg, unilateral weakness, sensory loss, reflex asymmetry, Babinski sign)

Total score: 4 suggests early stage dementia; 4-7 intermediate stage; 7 suggests vascular dementia.

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Lab tests

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

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Brain research

Brain imaging is now used to pinpoint visible pathological changes associated with other pathologies such as stroke, trauma, or malignant or benign tumors that may lead to cognitive impairment.

• MRI.
• Computed tomography.
• Positron emission tomography. New PET methods help diagnose the extent of brain damage from amyloid plaques.
• CSF analysis: Analysis of cerebrospinal fluid can help identify biomarkers that indicate the likelihood of developing Alzheimer's disease.

New diagnostic tests

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

New diagnostic tools in development:

• Developing new, precise methods for brain imaging
• Accurate diagnostic tests of mental abilities
• Determination of disease biomarkers in the blood or cerebrospinal fluid.

Genetic testing is not generally recommended for routine diagnosis of Alzheimer's disease, except in people with a strong family history.

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Differential diagnosis

Differential Diagnosis Between Alzheimer's Disease and Dementia with Lewy Bodies

Sign	Alzheimer's disease	Dementia with Lewy bodies
Pathomorphology	Senile plaques, neurofibrillary tangles, beta-amyloid accumulation in the cortex and subcortical gray matter	Lewy bodies in cortical neurons
Epidemiology	Affects women twice as often	Affects men twice as often
Heredity	Familial inheritance is seen in 5-15% of cases	It is rarely observed.
Fluctuations during the day	To some extent	Clearly expressed
Short-term memory	Lost in the early stages of the disease	Affected to a lesser extent; deficits concern attention more than memory
Symptoms of Parkinsonism	Very rare, develops in the late stages of the disease, gait is not impaired	Clearly expressed, usually occur in the early stages of the disease, there is axial rigidity and unstable gait
Dysfunction of the autonomic nervous system	Rarely	Usually there is
Hallucinations	Occurs in approximately 20% of patients, usually in the moderate stage of dementia	Occurs in approximately 80% of patients, usually at the onset of the disease, most often visual
Adverse reactions to antipsychotics	Frequent, may worsen symptoms of dementia	Frequent, sharply worsen extrapyramidal symptoms and can be severe or life-threatening

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Treatment Alzheimer's disease

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

Cholinesterase inhibitors modestly improve cognitive function and memory in some patients. Four of them are approved for use: donepezil, rivastigmine, and galantamine are generally equally effective; notacrine is used less frequently because of its hepatotoxicity. Donepezil is the drug of first choice because the daily dose is taken once and the drug is well tolerated by patients. The recommended dose is 5 mg once a day for 4-6 weeks, then the dose is increased to 10 mg/day. Treatment should be continued if functional improvement occurs after several months from the start of treatment, otherwise it should be discontinued. The greatest number of side effects are noted from the gastrointestinal tract (including nausea, diarrhea). Dizziness and heart rhythm disturbances occur less often. 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) has been shown to slow the progression of Alzheimer's disease.

Antidepressants are sometimes used in treatment to help control behavioral symptoms.

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Creating a safe and supportive environment

Follow these simple guidelines to help maintain the functional abilities of a patient with Alzheimer's disease:

• Always keep keys, wallets, cell phones and other valuables in the same place.
• Set up location tracking on your mobile phone.
• Use a calendar or board in your apartment to keep track of your daily chores. Get into the habit of checking off items that have already been completed.
• Remove unnecessary furniture, maintain order.
• Reduce the number of mirrors. People with Alzheimer's may sometimes not recognize themselves in a mirror image, which can be frightening.
• Keep photos of you and your relatives visible.

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Sport

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

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Nutrition

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

Nutritionists suggest eating the following foods:

• Shakes and smoothies. You can add protein powder to your milkshake (available at some drugstores).
• Water, natural juices, and other healthy drinks. Make sure that a person with Alzheimer's drinks several glasses of water a day. Avoid caffeinated drinks. They can cause anxiety, insomnia, and frequent urination.

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Traditional medicine

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

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 shown no benefit from dietary supplements containing fish oil.
• Curcumin. This herb has anti-inflammatory and antioxidant properties that may improve brain chemistry. So far, clinical trials have found no benefit for Alzheimer's disease.
• Ginkgo. Ginkgo is a plant extract. A large NIH-funded study found no effect in preventing or slowing the progression of Alzheimer's disease symptoms.
• Vitamin E: Although vitamin E cannot prevent the disease, taking 2,000 IU daily can slow its progression in people who already have the disease.

Estrogen therapy has not been shown to be useful in preventive treatment and may be unsafe.

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Forecast

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

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