What is Alzheimer's disease?

"Dementia" refers to the patient's progressive mental decline, which is mainly characterized by significantly poor memory and accompanied by abnormalities in behavior, emotion, and personality. This disease is called Alzheimer's disease because it is more common in the elderly; and because the disease was first confirmed and reported by Alzheimer in Germany, it is also called Alzheimer's dementia or Alzheimer's disease. . Previously, those who suffered from the disease before the age of 65 were called Alzheimer's disease, while those who developed the disease after the age of 65 were called Alzheimer's disease or Alzheimer's disease. In recent years, most scholars believe that there is little difference between the two types in terms of clinical manifestations and pathology, and there is no need to classify them.

The clinical manifestations of Alzheimer's disease mainly include the following four aspects:

Memory

Generally, after middle age, people tend to forget things consciously and have poor memory. In fact, this is mostly related to lack of concentration. Therefore, this kind of person can still remember things he cares about, and it is not really a memory loss. There are true memory impairments, and most of them are mild in the early stage, so it is really difficult to identify. It is often caused by poor memory of recent events. For example, it is difficult to remember phone numbers and house numbers. It becomes increasingly worse in the future, so that people lose things all day long. When going out to buy things, they either forget to pay, or they forget to pick up the things after paying, especially afterward. Most people with this disorder often cannot remember the names of friends or colleagues. Gradually, the memory of distant events becomes poor. In severe cases, he may even not know the way home after going out. At the same time, calculation skills are often not good, and accounts cannot be calculated from time to time.

In terms of thinking and judgment

It manifests as slow thinking, poor conversation, vague concepts of abstract nouns, inability to concentrate on study or work, difficulty in understanding and accepting new things, and the need for reasoning or judgmental thinking activities are often avoided or delayed.

In terms of personality and behavior

The patient's temper becomes eccentric, and the originally cheerful and disciplined person becomes exaggerated or cynical. People who were originally diligent gradually become lazy or become idle and nagging all day long; or they specialize in picking up rags; or their movements become slower and slower, and their interests become less and less; or they do not like to interact with others all day long, and the scope of social activities becomes smaller and smaller. The more it shrinks.

Emotional aspect

The patient showed mild depression, sluggishness and withdrawal, a feeling of incompetence at work, high mood, blind euphoria, and irritability. , with temperamental outbursts and impulsive attacks.

This disease has always been considered a degenerative disease of the brain. Recent studies have shown that there are certain neurobiochemical changes, especially changes in neurotransmitters; cholinergic neurons in the cerebral cortex and hippocampus Destruction or loss significantly reduces the content of choline acetyl-converting enzyme (CAT) and acetylcholine, impairing the synthesis, storage and release of acetylcholine. At the same time, it was found that the reduction of CAT was related to the severity of dementia, and that all areas in the brain containing acetylcholinergic neurons had similar lesions. The contents of other neurotransmitters were also reduced to varying degrees, and somatostatin was also reduced.

In terms of pathology, the disease manifests as: widespread brain atrophy (especially the temporal lobe, frontal lobe, and parietal lobe); enlargement of the ventricles, widening of the brain sulci, and narrowing of the brain gyri; degeneration of related nerve cells. loss, reduction. In addition, there are also more special lesions of this disease: senile neurites appear in the brain tissue, which are star-shaped silver-stained cell fragments left after the degeneration of nerve cells. Secondly, neurofibrillary tangles appear in the nerve cytoplasm, which is the result of degeneration and degeneration of neurofibrils, which is different from the microfilaments and microtubules in normal nerve cells.

Dementia refers to pathological memory and other cognitive dysfunction. Alzheimer's disease or Alzheimer's disease is the most common form of dementia. The disease affects 5% to 10% of people over 65 years old, and a higher percentage among people over 85 years old. Typical early manifestations are early memory function and attention disorders, followed later by impairments in language skills, visuospatial positioning, abstract thinking and judgment, and personality disorders. There is currently no effective treatment.

The diagnosis of AD, in addition to relying on the above-mentioned clinical manifestations, also depends on whether there are special pathological changes in brain tissue: neurofibrillary tangles formed by cytoskeletal microfilaments in neurons, also known as neurofibrillary tangles. Deposition of amyloid (senile plaques) and associated neuronal loss. Histopathological changes are most obvious in the following brain areas: neocortex, limbic system (especially hippocampus, amygdala, entorhinal cortex), and some basal forebrain nuclei, locus coeruleus and raphe nucleus.

Although the cause of AD is still unclear, the identification of a mutated gene in a small number of families with early-onset cases provides an opportunity to understand some aspects of AD. Approximately 5% of AD patients are familial. Previous studies have long suspected that the problem of familial AD lies in chromosome 21. Part of the reason is because of another neurological disease - Down syndrome. Its histopathological changes are similar to AD, with spots and tangles, and early symptoms. Dementia. This patient has an extra copy of chromosome 21. In addition, AD patients have obvious amyloid deposits, which also suggests that there may be something wrong with the gene encoding pre-amyloid protein (APP). Goldgaber cloned the APP gene and found that it was on chromosome 21. This observation eventually led to the idea that those patients with familial early-onset AD do indeed have missense mutations in the APP gene.

The discovery of APP gene mutations in familial early-onset AD patients is obviously of great significance, because it suggests that patients with other forms of AD may also be related to APP. In order to test this point of view, biochemists conducted an experiment. They fixed a derivative of APP on nitrocellulose, and then took the cerebrospinal fluid of AD patients to check whether there was a protein that binds with high affinity to APP. The experimental results found a protein with high affinity for APP derivatives, namely apolipoprotein, which is a cholesterol chaperone in serum.

Since then, the above discovery has shown its importance. Biochemists have discovered that a DNA marker on chromosome 19 of some family members of late-onset AD patients is related to the disease, and this chromosome happens to contain the gene encoding the ApoE isoform, called the E4 allele. This result led to the study of other alleles of ApoE, a member of the late-onset AD family. It was found that the occurrence rate of E3 allele in the general population was 0.78, and that of E4 was 0.14. Biochemists have found that the occurrence rate of E4 in families of late-onset AD patients is 0.52, which is almost four times that of the normal population. Therefore, they concluded that inheritance of the E4 allele is a risk factor for late-onset AD disease. This is true. People who are homozygous for E4 are eight times more likely to develop AD than people who are homozygous for E3. Late-onset AD patients have no E4 copies in their families, and only 20% develop AD by the age of 75, while 90% of people with two copies of E4 develop AD. Even in non-familial AD, there is an association with the E4 allele, which is an important finding because non-familial AD is the most common AD disease.

There is a question that needs to be understood. Is the E4 allele of ApoE itself responsible for the increased risk of disease? Or is another closely related gene on chromosome 19 responsible for this? Facts have shown that , plaques in the brains of early-onset AD patients can combine with ApoE, which seems to indicate that the E4 allele itself is related to the pathogenesis of this disease. In contrast, mutations in the E4 allele do not appear to be directly associated with late-onset AD, but rather with an increased risk of AD. However, there is still an important point worth noting: Although some patients have familial early-onset AD due to APP mutations, they do not have the E4 allele, which illustrates the heterogeneous nature of AD.

The current issue is to clarify the relationship between the E4 allele and the increased risk factors for the onset of AD. Understanding this risk factor can provide a valuable tool for analyzing the molecular pathogenesis of AD, the most common form of dementia.

Almost normal elderly people have varying degrees of brain atrophy and may also have varying degrees of memory loss, but they do not all eventually develop into dementia. It can be seen that although age has an important relationship with this disease, not all elderly people are bound to develop dementia.

The diagnosis of this disease is mainly based on its clinical manifestations. However, because the early manifestations are mild and develop slowly, it is easy for relatives and friends to think that it is a manifestation of the health decline of the elderly and be ignored, thus delaying the early diagnosis. Diagnosis and treatment.

Let’s talk about dementia syndrome for reference in differential diagnosis.

Multiple cerebral infarction dementia

There is often a history of stroke and many signs of neurological limitations. Special examinations such as brain CT and MRI can be used to identify it.

Dementia caused by brain trauma

For example, boxers have suffered multiple brain traumas, and the so-called boxing dementia is a well-known type. In addition, progressive dementia may also occur in chronic subdural hematoma, especially in the elderly, who may not necessarily have a clear history of trauma, or the trauma may have been relatively minor at the time and have been forgotten. Headaches are not necessarily present, and mental disorders often fluctuate. Special examinations such as brain CT can confirm the diagnosis.

Intracranial inflammation

Many inflammations have symptoms of dementia during the course of the disease or as sequelae, such as tuberculous, fungal, viral meningitis or encephalitis. Another example is neuromexin, lentivirus, acquired immunodeficiency syndrome, etc., which can cause dementia. All these diseases can be identified through a detailed medical history and relevant physical examination and special tests.

Toxic diseases

Frequent exposure to certain metals (such as aluminum, lead, mercury, manganese, etc.) or taking certain drugs can also lead to diseases with dementia. Only a detailed medical history and various targeted examinations can serve as the basis for differential diagnosis.

Dementia syndrome associated with other brain degenerative diseases

Such as multiple sclerosis, Huntington's disease, corticostriatal myelopathy, during the course of the disease or If there are symptoms of dementia, it is not difficult to confirm the diagnosis through the course of the disease, physical examination, and special examinations such as brain CT.

Dementia syndrome associated with other metabolic diseases

Such as liver, kidney and other diseases, especially in the late stages, may lead to varying degrees of dementia. As long as the medical history is taken seriously, With the corresponding examination results, it is not difficult to make a differential diagnosis.

Other demyelinating diseases and lipodystrophy diseases

This disease often has symptoms of dementia, such as leukodystrophy, familial amaurotic dementia, etc. The former mostly occurs in Children, and often have familial genetic tendencies, the latter can be identified by an obvious family history.

Although many of the above dementia syndromes may be diagnosed through medical history and corresponding examinations and special examinations, in fact there are still about 5% of dementia patients whose causes are unknown and cannot be determined even through autopsy. .

The prevention and treatment of this disease has always been an urgent problem to be solved. Currently, only symptomatic treatment, such as Chinese and Western medicines that improve cerebral circulation, brain metabolism and cerebral blood rheology factors, can be tried. In addition, strengthening psychological therapy, physical therapy, etc. can also be helpful. Through these measures, it is possible to alleviate some symptoms, delay the progression of the disease, and improve the quality of life.

In view of the relationship between this disease and genetic factors, various aspects are engaged in research in this area, and some progress has been made. Gene therapy that may be carried out in the future should be the most promising prevention and treatment measure.