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Alzheimer’s disease

 
Last reviewed by: Aleksey Portnov , medical expert, on 25.06.2018
 

Alzheimer's disease is caused by a progressive loss of cognitive abilities, and characterized by the formation of senile plaques and amyloid accumulation and neurofibrillar glomes in the cerebral cortex and subcortical gray substance.

Alzheimer's disease is a neurological disease which is the most common cause of dementia, constitutes more than 65% of dementia in the elderly people. The disease is twice more common in women than men that is, particularly, associated with the longer life expectancy of women. Alzheimer's disease affects about 4% of people in ageaged from 65 to 74 years and more than 30% in the age of more than 85 years. Predominance of number of patients in developed countries is associated with an increase of number of elderly people in them.

Causes of Alzheimer’s disease

Most cases of the disease are sporadic, they have a late onset (in patients over 60 years) and an unknown etiology. However, from 5 to 15% cases have a familial character, a half of these cases has an earlier onset (in age less than 60 years), and is usually associated with specific genetic mutations.

Typical morphological changes are the extracellular accumulation of the α-amyloid and the intracellular neurofibrillar glomes (paired helical filaments), the development of the senile plaques and the loss of neurons. There are usually a cortical atrophy, reduced glucose consumption, as well as a decrease in cerebral perfusion in the parietal lobe, temporal cortex and prefrontal cortex.

At least five specific genetic loci, located on the 1st, 12th, 14th, 19th and 21th chromosomes, influence on the onset and progression of Alzheimer's disease. In the development of the disease genes, encoding processing of the precursor protein presenilin I and presenilin II, are is involved. Mutations in these genes can alter processing of α-amyloid precursor protein, leading to the accumulation of fibrillar aggregates of the α-amyloid. α-amyloid can facilitate death of neurons and formation of the neurofibrillar glomes and senile plaques which consist of degenerative changes of axons and dendrites, astrocytes and glial cells, located around the amyloid nucleus.

Other genetic determinants include alleles of apolipoprotein E (apo E). Apolipoprotein E influences on the accumulation of α-amyloid, cytoskeleton integrity and the effectiveness of neuron recovery. Risk of Alzheimer's disease is greatly increased in people, having four alleles, and is reduced in those ones, who have two alleles.

Other common abnormalities include an increase of concentration in cerebrospinal fluid and brain of protein taurine (components of neurofibrillar glomes and α-amyloid) and a decrease of choline acetyltransferase and various neurotransmitters (in particular, somatostatin).

The relationship of the environmental factors (exogenous) (including low levels of hormones, exposure to the effects of metals) and Alzheimer's disease is still under study, but no correlation has been confirmed yet.

Symptoms of Alzheimer’s disease

Symptoms and signs of Alzheimer's disease are similar to those ones in other types of dementia with early, intermediate and late stages of disease development. Short-term memory loss is often the first symptom. The disease progresses steadily, but may also have some plateau time intervals. Behavioral disorders (including vagrancy, irritability, loudness) are usual.

Diagnostics of Alzheimer’s disease

Usually, diagnostics is similar to that one for other types of dementia. Traditionally, diagnostic criteria for Alzheimer's disease include dementia confirmation with the help of physical examination and documentation of results of formalized testing of mental status; deficit, found in 2 or more cognitive domains, gradual onset and progressive deterioration of memory and other cognitive functions; lack of consciousness disorders; beginning after the age of 40 years; most often after the age of 65 years; an absence of systemic diseases and brain diseases which can be regarded as the cause of progressive memory loss and cognitive functions. Nevertheless, some 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. Set of evaluation tests (for instance, Khachinsky IschaemicIschemic Score) can help to distinguish vascular dementia from Alzheimer's disease. Fluctuations of cognitive functions, parkinsonismParkinsonism symptoms, well-designed visual hallucinations and the relative preservation of short-term memory confirm rather the diagnosis of dementia with Loewi bodies than Alzheimer's disease. Patients with Alzheimer's disease, unlike other dementia, often look more well-groomed and neat. Approximately in 85% of patients with Alzheimer's thorough collected past medical history and neurological examination allow to confirm the correct diagnosis.

Modified Khachinsky Ischaemic Score

Signs

Scores

Sudden appearance of symptoms

2

Stepwise increase of symptoms (disturbances) (for example, deterioration - stabilization - deterioration)

 

Oscillation (fluctuation) of symptoms

2

Normal orientation

1

Individual personality traits are relatively preserved.

 

Depression

1

Somatic complaints (for instance, tingling sensation in the hands and awkwardness)

 

Emotional lability

1

Arterial hypertension in the present or in the past medical history

2

Stroke in the past medical history

 

Confirmation of atherosclerosis presence (for example, pathology of peripheral arteries, myocardial infarction)

 

Focal neurological symptoms (for instance, hemiparesis, equilateral hemianopsia, aphasia)

 

Focal neurological signs (for example, unilateral weakness, loss of sensitivity, asymmetry of reflexes, Babinski's phenomenon)

 

Total number of scores: 4 suggests an initial stage of dementia (for example, Alzheimer's disease); 4-7 - an intermediate stage; 7 suggests vascular dementia.

Differential diagnosis

Differential diagnostics between Alzheimer's disease and dementia with Loewi bodies

Sign

Alzheimer's disease

Dementia with Loewi bodies

Pathomorphology

Senile plaques, neurofibrillar glomes, accumulation of beta-amyloid in the cortex and subcortical gray substance

Loewi bodies in the cortical neurons

Epidemiology

The women are twice as commonly affected as men

The men are twice as commonly affected as women

Heredity

Family inheritance can be observed in 5-15% of cases

It is observed rarely

Fluctuations during the day

To some extent

Clearly expressed

Short-term memory

It is lost in the early stages of the disease

It is suffered in a lesser degree; deficit relates in greater extent to attention than to memory

Parkinsonism symptoms

They develop very rarely in the later stages of the disease, a gait is not disturbed

They are clearly expressed, and usually occurred in the early stages of the disease, there is an axial rigidity and gait instability

Dysfunction of the autonomic nervous system

Rarely

Usually present

Hallucinations

They occur approximately in 20% of patients, generally at the stage of the moderate dementia 

They occur approximately in 80% of patients, usually in the onset of the disease, most often visual ones

Adverse reactions to antipsychotic agents

They are frequent, can aggravate symptoms of dementia

They are frequent, dramatically worse extrapyramidal symptomatology, and can be severe or life-threatening

 

Who to contact?

Treatment of Alzheimer’s disease

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

Cholinesterase inhibitors modestly improve cognitive function and memory in some patients. Four of them are approved for application in general, such as donepezil, rivastigmine and galantamine are equally effective, notacrine is used less frequently, because it has hepatotoxicity. Donepezil is a drug of 1st choice, as a daily dose is administered once, and patients tolerate the drug well. The recommended dose is 5 mg once a day for 4-6 weeks, then the dose increases to 10 mg/day. Treatment should be continued, if after a few months from the start of the administration functional improvement has appeared, otherwise, it should be discontinued. The most number of side effects is observed in the gastrointestinal tract (including nausea, diarrhea). Less frequently dizziness and cardiac rhythm disturbance are observed. Side effects can be minimized by gradual dose escalation.

Recently approved for application antagonist N-methyl-O-aspartate of receptors memantine (5-10 mg orally per one administration) has demonstrated slowness of Alzheimer's disease progression. Efficacy of high doses of vitamin E (1000 IU orally, once daily), selegiline, nonsteroidal antiinflammatory drugs (NSAIDs), Ginkgo biloba extract and statins has not been established. Estrogen therapy has revealed no application in preventive treatment and can be unsafe.

Drugs

Forecast

Despite the fact that the rate of disease progression varies, cognitive impairment is unavoidable. The median survival time from the time of Alzheimer's disease diagnosis is 7 years, although, this number is debated.

It is important to know!

Alzheimer's disease is the most common cause of dementia in the western hemisphere, accounting for more than 50% of its cases. The prevalence of Alzheimer's disease increases with age. In women, the disease is more common than in men.

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