Alzheimer’s disease
Definition. Causes of disease
Alzheimer’s disease is a chronic neurodegenerative disease with a slow onset and significant deterioration over time. In 70% of cases, Alzheimer’s disease leads to dementia.
Etiology. Risk factors
The disease is currently poorly understood. It is believed that 70% of Alzheimer’s disease is due to genetic causes; for example, it was recently discovered that the risk of developing the disease is higher in women with the APOE ε4 allele (mutation in the MGMT gene). Other risk factors include brain injury, depression, a history of endocrine disease (hypothyroidism), and estrogen deficiency in women.
Associated diseases
Recent studies show that hypertension, hyperlipidemia, hyperhomocysteinemia, diabetes mellitus, metabolic syndrome, insulin resistance, heart disease, and a history of stroke increase susceptibility to Alzheimer’s disease.
Statistical data
Alzheimer’s disease is the most common form of dementia, occurring in 60-70% of cases. About 50 million people suffer from dementia worldwide, and 10 million new cases are diagnosed every year. In developed countries, Alzheimer’s disease is one of the most expensive diseases.
Prevalence and risk factors
The disease is more common in women. It is presumably due to the following factors:
- women have a longer life expectancy than men, and age is the most significant risk factor for developing Alzheimer’s disease;
- The risk of developing the disease increases by 70% for people with depression, and it is more common in women;
- lower educational attainment is associated with an increased risk of dementia; in some countries, women have lower educational attainment than men;
- hypertensive disorders are common in pregnancy and are associated with an increased risk of cognitive deterioration even decades after pregnancy.
Symptoms of Alzheimer’s disease
Signs of early-stage Alzheimer’s disease are often mistaken for typical signs of aging.
Short-term memory loss is the most common early symptom of Alzheimer’s disease, which means that the patient has difficulty remembering recent events. In a third of cases, the disease can be recognized by behavioral changes.
As the disease worsens, the following symptoms occur:
- speech problems;
- disorientation;
- mood swings;
- loss of motivation;
- decreasing criticism;
- patients cannot remember the right word and must replace it with another word (paraphasia), but they repeat what they have said well.
- over time, there has been difficulty naming objects (anomia).
- already at an early stage, there are difficulties with understanding complex grammatical structures (semantic aphasia), which is then joined by alienation of word meaning.
An essential sign of Alzheimer’s disease is an impaired ability to cope with everyday life. The disease causes problems with self-care and behavioral disorders.
Classification and stages of development of Alzheimer’s disease
The typical phenotype of Alzheimer’s disease is a combination of severe hippocampal-type mnestic impairment with acoustic-mnestic aphasia, visual-spatial impairment, and apraxia.
Three atypical phenotypes of Alzheimer’s disease (non-amnestic):
- with a leading aphasic defect (logopenic variant of primary progressive aphasia);
- with dominant visual-spatial disorders (posterior cortical aphasia);
- predominantly with dysregulatory disorders (frontal variant of Alzheimer’s disease).
The disease is also subdivided into early-onset forms, often with a positive family history (before age 65) and late-onset forms (over age 65). They differ in pathogenesis, genetic factors, and rates of progression.
The three stages of Alzheimer’s disease:
First (pre-dementia, early dementia): patients are self-caring but need help with financial matters, cooking, etc.
The second (moderate dementia): dependence on outside help increases – patients are unable to dress themselves, perform hygienic procedures, and stay at home unattended for a long time.
Third (severe dementia): patients cannot perform any of the usual daily activities without the help of others.
The transition from one stage to another correlates with a decrease in scores on the BMSS (Brief Mental Status Scale), which is a reliable tool for tracking disease progression.
Diagnosis of Alzheimer’s disease
Difficulties in early diagnosis of Alzheimer’s disease are largely due to the “masked” nature of the disease during this period when there are no obvious external signs of dementia. To diagnose and determine the tactics of patient management, it is necessary to identify the nature and severity of cognitive impairment.
Neuropsychological test
The primary method of assessing cognitive function is a neuropsychological examination performed by a physician trained in these research methods. In some countries, it is practiced to examine patients by their relatives using scales to assess cognitive functions: Montreal Cognitive Scale, Addenbrooke’s, Brief Mental Functions Examination Scale.
Biomarkers of Alzheimer’s disease
Molecular diagnosis at an early stage of the disease also creates prospects for early prescription of treatment for Alzheimer’s disease. Determination of biomarkers in plasma is a less invasive alternative for the diagnosis of Alzheimer’s disease. Biomarkers are categorized into biomarkers of amyloid accumulation and biomarkers of neurodegeneration. The significant biomarkers reflect amyloid pathology (extracellular accumulation of Aβ1-40/1-42) or intracellular inclusions of neurofibrillary tubules (hyperphosphorylated tau).
MRI and CT scans of the brain
Modern neuroimaging techniques – magnetic resonance imaging and computed tomography of the brain – are expanding the diagnostic possibilities of lifetime diagnosis of Alzheimer’s disease.
MRI and CT scans are performed to identify treatable causes of dementia and abnormalities that may exacerbate symptoms. Structural changes on MRI are more predictive of further cognitive changes than cerebrospinal fluid biomarkers.
The localization of cerebral microhemorrhages is a differential diagnostic sign of the leading pathological process. In the case of Alzheimer’s disease, cortical localization of microhemorrhages is observed; in the case of dyscirculatoryencephalopathy or vascular dementia, microhemorrhages in deep parts of the brain will be visualized.
One of the most promising methods for diagnosing Alzheimer’s disease is positron emission tomography with a ligand that binds to amyloid (PiB); however, amyloid accumulation and capture of the corresponding ligand increase during the stage of moderate cognitive impairment, but no further accumulation occurs after conversion to dementia.
Treatment for Alzheimer’s disease
Alzheimer’s disease does not yet have a cure. But thanks to a group of new drugs and symptomatic treatment of Alzheimer’s, it may be possible to make the decline in the intelligence of patients more gradual.
Medications
There are several drugs for dementia treatment, and they are primarily for Alzheimer’s disease, but they are often used for dementias of other origins as well.
Such remedies include:
- Cholinesterase inhibitors (donepezil, rivastigmine, galantamine)
- NMDA-glutamate receptor blockers (acatinol memantine).
- Anti-amyloid monoclonal antibodies – are the first disease-modifying therapies for AD that achieve slowing of clinical decline by intervening in the basic biological processes of the disease. These are breakthrough agents that can slow the inevitable progression of AD into more severe cognitive impairment.
All these treatment options are available in more than 999 hospitals worldwide (https://doctor.global/results/diseases/alzheimers-disease). For example, Monoclonal antibodies therapy (mAbs) can be given in 21 clinics across Germany (https://doctor.global/results/europe/germany/all-cities/all-specializations/procedures/monoclonal-antibodies-therapy-mabs).
Relief of the mental and behavioral disorders that accompany Alzheimer’s disease
Antidepressants and neuroleptics are also used to treat co-occurring mental and behavioral disorders.
Supporting methods
There are also non-drug methods of treatment, such as training intellectual functions. Neuropsychological rehabilitation allows you to stimulate the development of new neural networks by training working nerve cells.
Prediction
As public awareness of dementia increases, care needs will also increase, and significant costs will be required to organize it. For the time being, informal family-based care is the predominant approach. Efforts to improve the quality and accessibility of care will require investment in primary prevention measures, and it may be possible to control the “epidemics” of dementia in different regions of the world. Improving education and addressing vascular risk factors are critical primary prevention targets.
Prevention
Today, one of the main goals of prevention is to create various new forms of out-of-hospital care for elderly people and patients in order to improve the diagnosis of cognitive impairment of varying severity and the earlier detection of diseases. For this purpose, memory clinics and Alzheimer’s centers have been established in developed countries.
It was recently found that older adults were 40% less likely to develop Alzheimer’s disease if vaccinated against influenza at least once. The protective effect of the vaccine was maintained for four years. The reasons for this are still unclear. There are three theories:
- By preventing or easing the course of influenza, the vaccine prevents the development of systemic inflammation that contributes to Alzheimer’s disease;
- The vaccine affects immune cells in the brain, and they are better able to cope with the disorders associated with Alzheimer’s disease;
- immunized people take better care of their health, which reduces their risk of Alzheimer’s disease overall.
Life expectancy
On average, people with Alzheimer’s disease live 3-11 years after the disease is diagnosed, but some live 20 years or more. Life expectancy depends on the degree of impairment at diagnosis.