Menopause and Alzheimer's Syndrome
Introduction
Introduction to menopause and Alzheimer's disease syndrome Although Alzheimer's disease (Alzheimersdisease AD) is a primary degenerative brain disease with unknown etiology, its pathogenesis and estrogen levels are related to brain structural function. Alzheimer's disease has characteristic neuropathological and neurobiochemical changes. It is often insidious onset and develops slowly and steadily over a period of several years, often dying 6 to 12 years after onset. Early-onset dementia syndrome In 1907, Alzheimer first reported that a 50-year-old woman suffering from dementia was named "Alzheimerdisease, AD", ie Alzheimer's disease, another type of late-onset dementia, once called For "Alzheimer's disease." In recent years, it has been recognized that the neuropathological changes of the two diseases are the same and thus can be regarded as the same disease. basic knowledge Sickness ratio: 8% Susceptible population: menopausal women Mode of infection: non-infectious Complications: dementia
Cause
Menopause and the cause of Alzheimer's disease syndrome
Causes
The main causes of Alzheimer's disease are:
Abnormal biochemical transmitters in the central nervous system (20%):
The decrease in the concentration and activity of choline acetyltransferase leads to a decrease in the presynaptic synthesis of acetylcholine in neurons, especially in the hippocampus and temporal lobe cortex, which is closely related to near memory and transient memory. In severe cases, dopamine, Systems such as norepinephrine and serotonin are also damaged.
Other (20%):
There are also virology, immune disorder theory and brain damage theory.
The risk factors for the disease are heredity, advanced age, insufficient blood supply to the brain, low education, Down syndrome, head trauma, hyperlipidemia, etc. The protective factors are vitamin B6, B12, folic acid and the like.
About <10% of patients with a positive family history have genetic defects in the disease, such as: early onset and amyloid precursor protein (APP) gene mutation on chromosome 21, located on chromosome 14 premature gene 1,1 premature gene 2 Mutation-related, delayed cases are associated with the apolipoprotein E (ApoE) 4 allele located on chromosome 19, and most patients may have a combined effect of multiple causes. The related hypotheses are: neurotoxic effects of amyloid beta; beta starch Protein-like deposition causes inflammatory cell infiltration, at least in relation to disease progression; ApoE promotes the deposition of amyloid beta and inhibits the growth of neuronal processes.
Genetic factors (10%):
There is a mild genetic predisposition, and the incidence of immediate family members is four times higher than that of the general population.
Metal aluminum accumulates in the brain (5%):
Neuronal protein synthesis, which can lead to cellular and metabolic disorders, is blocked, but its role in etiology is not yet certain.
Pathogenesis
The pathology of the disease mainly manifests as brain atrophy, with the most obvious sputum, apex and forehead area, brain weight can be reduced by 20% to 30%, cerebral cortical nerve cells are reduced by 35% to 40%, neuronal synapses are reduced and regressed. Sexual degeneration, senile plaques distributed in a wide range of cerebral cortex, neurofibrillary tangles and particle vacuolar degeneration are three major features of the pathology of this disease.
1. Estrogen affects brain structure and function
The effects of estrogen on brain structural function involve three aspects: nerve cells, vascular structures, and neurotransmitters:
(1) nerve cells: estrogen has neurotrophic effects: in vitro culture studies of fetal rat hippocampus, basal forebrain, and cerebral cortical neurons show that small doses of estrogen can promote nerve cell axons, dendritic growth, and synaptic In the formation, estrogen can also promote the development of astrocyte cells and support neuronal function. Toran-Allerand CD found that rodent basal forebrain cholinergic neurons have both estrogen receptor and nerve growth factor (NGF). Receptors, estrogen can directly nourish these neurons and act as NGF cofactors, thereby promoting neuronal differentiation, survival, regeneration, and maintaining their plasticity.
Estrogen has neuroprotective effects: Singh M (1995) reported that after ostradiol in ovariectomized female rats, more neurons were retained in the basal forebrain, and NGFmR-NA expression also returned to normal, showing beta amyloid. In vitro culture of oxidized free radicals and glutamate, estrogen protects hippocampal neurons from damage, estrogen increases BCL-X protein expression, and reduces apoptosis caused by amyloid beta Estrogen inhibits the production of ApoE, promotes the production of soluble amyloid protein by amyloid precursor protein (APP), and decreases the production of amyloid beta; it also promotes repair of injured brain cells in adults.
(2) vascular structure: estrogen has the effect of dilating blood vessels and improving blood supply to the brain; the study of regional cerebral blood flow (rCBF) by single photon emission computed tomography (SPECT) or positron emission tomography (PET), It has been reported that postmenopausal women have low rCBF, especially in hot flashes, ERT improves rCBF by about 22%, especially in temporal lobe, hippocampus, estrogen promotes the expression of nitric oxide (NO) synthase, and decreases IL-1. Activity, blocking the production of IL-6, thereby reducing the inflammatory response caused by amyloid beta.
(3) Estrogen promotes the synthesis of various neurotransmitters: Luine VN et al. (1985) found choline acetyltransferase in the basal forebrain nucleus and its projection area after injection of estradiol into ovariectomized rats. (Enzymes necessary for the synthesis of acetylcholine) activity increased, and in a dose-effect relationship; estrogen antagonists can block this effect, estrogen also reduces monoamine oxidase (MAO) activity, increase monoamine neuron in the brain, serotonin nerve The role of the receptor, estrogen may have antidepressant anxiety, thereby increasing the enthusiasm of patients.
Animal behavior studies have shown that learning and memory function are related to estrogen. The above studies also show that the memory function of ovariectomized female rats is better than that of animals without estrogen.
2. Pathophysiological changes in Alzheimer's disease
It is a diffuse cerebral cortical atrophy, a large number of nerve cells and synaptic degeneration and disappearance, with the basal forebrain and hippocampus, the neocortical cholinergic neurons (critical for learning, memory function), the most serious, extracellular amyloid Deposition, formation of senile plaques; accumulation of abnormally phosphorylated tau protein in cells, formation of neuronal fiber entanglement, reduced synaptic density, low activity of choline acetyltransferase necessary for the synthesis of acetylcholine (ACH), glutamate, dopamine (DA), serotonin (5-HT), also involved in noradrenergic neurons.
3. Estrogen and AD disease
It is reported that the prevalence of this disease in older women is 2 to 3 times higher than that of older men. The adjustment of women's average longevity is still higher than that of men. Those with a history of myocardial infarction have more AD, and those with AD are thinner. It is easier to fracture. Honjo (1995) reported that the blood estrone sulfate concentration of patients with this disease is lower than that of age-free controls. The blood ApoE level is too high in patients with blood E2<73.3pmol/L (20pg/ml), Schonknecht P (2001) reported that E2 levels in cerebrospinal fluid of women with AD were lower than those without AD and were inversely related to the concentration of -A in cerebrospinal fluid. These phenomena suggest that estrogen deficiency may increase the incidence of AD, and estrogen replacement therapy (ERT) may reduce the risk of disease. Sex.
(1) Epidemiological study on the relationship between estrogen replacement therapy (ERT) and AD: 4 out of 5 retrospective case-control studies after 1994 showed that the risk of this disease was compared with those without ERT. The odds ratio was 0.33 to 0.60; however, the case-control study of Seshadri s (2001) reported no significant difference. Three prospective cohort studies from 1993 to 2000 showed the relative risk of AD or death from AD in ERT patients (RR). It was 0.69 to 0.40; and Paganini-Hill's study also showed that the estrogen used was large in dose, long in treatment, or obese, and the RR was low in menarche.
(2) Clinical study on ERT in the treatment of AD patients: 6 short-term, controlled small-sample clinical studies in 1993, showing that ERT is effective in some AD patients, mainly attention, word memory, visual memory improvement, but After the drug was stopped, there was still a uterine bleeding reaction. In 2000, Mul-natd RA reported a randomized double-blind controlled study of 120 patients with mild and moderate AD in 32 centers in the United States. The application of estrogen was 0.625 mg/d. 1.25mg/d 1-year AD patients were followed up for 15 months, compared with placebo AD patients, clinical overall impression change score, mood, cognitive function (memory, attention, language), motor function, daily Life ability and other aspects have not been shown to delay disease progression or improve symptoms. Henderson VW et al (2000) 36 patients with mild to moderate AD 16 weeks of randomized double-blind controlled study and 50 patients with AD PN such as 12 weeks CEE The results of a randomized, double-blind, controlled trial also showed that ERT had no effect on AD, and a small sample of two female, progesterone (methamphegestrel, MPA) combination therapy showed that MPA counteracted the effects of estrogen.
(3) Can ERT improve the cognitive function of elderly women without AD? Report on the improvement of word memory and fluency, visual memory, Yaffe K (2000) reported that it is only effective for women with APOE4-negative, APOE4-positive women are not effective, but Four studies showed that ERT was ineffective, and the reasons for the inconsistency may be multi-faceted. For example, the number of cases is small, the research population is different, the test method or ERT program is different, the follow-up period is short, and the menopausal period is short.
(4) The role of ERT in preventing the onset of AD: What factors cause selective neuronal degeneration in AD patients is still unclear. According to the results of basic, epidemiological and clinical studies, estrogen may regulate this process. Estrogen deficiency may increase the susceptibility of cholinergic neurons in the basal forebrain and hippocampus, which may be one of the pathogenesis factors. In view of the beneficial effects of estrogen on nerve cells, cerebrovascular structures and neurotransmitters, it is possible Preventing or delaying the onset of AD, if confirmed, will have great significance, but large-scale, prospective, randomized, interventional studies are needed to determine whether ERT has a preventive effect on AD, and the safety of ERT is appropriate. The dosage and course of treatment are also to be explored.
Prevention
Menopause and prevention of Alzheimer's disease syndrome
People over the age of 50 can have some chronic degenerative symptoms, such as memory loss, slow response, mental retardation, depression, and even dementia, which can be roughly divided into two forms: one is cerebrovascular dementia, accounting for about 50%; The second is Alzheimer's type dementia, accounting for about 25%; the rest is mixed type. It is reported that the United States is more common with Alzheimer's type dementia. This type of dementia is closely related to the conception. The Japanese are made up of traditional diet. After switching to the Western diet, there is a significant increase in Alzheimer's type dementia. It can be seen that prevention of senile dementia and diet regulation is crucial. Most researchers believe that conditioning diet may be prevention of Alzheimer's disease (Alzheimer) , AD) One of the most effective methods, the diet should be comprehensive, balanced, scientific and reasonable, and reasonable.
1. Pay attention to rice, flour, corn, millet and other staple foods to ensure the important source of heat energy for brain cells. Because brain cells can only use glucose as energy, they are required to consume enough carbohydrates, and some people wake up in the morning. No time to eat breakfast, or unhealthy habits without breakfast, so that people are hungry in the morning, blood sugar is lower than the normal supply level, resulting in insufficient nutrient supply to the brain. If this is the case, it will definitely damage the health and thinking function of the brain. .
2. Pay attention to the intake of fat, especially essential fatty acids. The essential fatty acids are rich in vegetable oils such as soybean oil, sesame oil and peanut oil. It is an unsaturated fatty acid. The brain is 35% structurally protein, and about 60% is lipid. Therefore, it is edible. The choice of fat can not be underestimated, the enhancement and decline of memory, essential fatty acids play a major role, in addition, soybean oil is rich in lecithin, acetylcholine deficiency is the main cause of senile dementia, the memory loss of the elderly, the reason and the lack of acetylcholine content Certainly, acetylcholine is an essential compound for the transmission of nervous system information. Lecithin is a raw material for the conversion of acetylcholine into the brain. Supplementation with lecithin can increase acetylcholine. If long-term supplementation with lecithin can increase memory, thinking, analytical ability, and change Be smart, delay functional decline, prevent or delay the onset of senile dementia, lecithin can also improve blood supply to the brain, human to middle-aged, serum cholesterol and neutral fat deposits in the blood vessel wall, causing blood flow to be blocked, leading to insufficient blood supply to the brain , causing a large number of brain cells to die, easily causing early Dementia, lecithin can make serum cholesterol and neutral fat particles emulsified and keep it in suspension, so that the blood vessels are smooth, nutrients and oxygen are continuously supplied to the brain. Because lecithin has these two major functions, medical scientists It is called the nemesis of senile dementia. At present, Japanese scientists intend to extract lecithin from soybeans to develop drugs for the treatment of senile dementia. The foods containing lecithin are soybeans and their products, fish brain, egg yolk, caviar, Pig liver, sesame, yam, mushrooms, peanuts, etc.
It should also be pointed out that fat is an important place for the production of estrogen in addition to the ovary in the body. We know that older women are the high-risk population of this disease (male: female 1.5:1 to 2:1), and the latest research shows that hormone replacement therapy is accepted. Postmenopausal women have higher neuronal cell density, but lower cell membrane turnover rate, similar to that of young women, and the opposite is not accepted, suggesting that hormone replacement therapy may soothe brain local tissue affected by Alzheimer's disease The degenerative condition, so older women should not be vegetarian, supplemented with appropriate fat to relieve the low estrogen caused by ovarian decline.
3. A large intake of vitamin B12 and folic acid is beneficial to prevent senile dementia. The blood vitamin B12 content is below the lower limit of 1/3 of the normal range, and the possibility of senile dementia is more than three times; the folic acid content is also low. The possibility of suffering from this disease is increased by 2 times. This is because the deficiency of vitamin B12 can change the structure and action of transcobalamin I in the body, leading to the failure of immunoglobulin production, weakening of disease resistance, and serious damage to nerve cells. The study also found that people with vitamin B12 and folate deficiency had the highest concentration of cysteine (a potentially harmful amino acid), and their content was 1/3 of the normal range, and the likelihood of dementia was 35 times higher. Therefore, special attention should be paid to supplementing enough vitamin B12 and folic acid from food. This is convenient, effective, safe and economical. The foods rich in vitamin B12 include shellfish, eggs, milk, animal kidneys and various fermented soy products. (such as bean curd); folic acid is widely found in a variety of animal and plant foods, folic acid-rich foods include green leaves and yellow leaf vegetables, yeast, animal liver and kidney.
4. Pay attention to the indispensable trace elements and macro elements in the brain. For example, iodine is an important component of thyroxine. If it is lacking, it will be irritated due to hypothyroidism, weak interest, decreased intelligence, and iodine present in each. In marine products, zinc is an essential substance for the synthesis of brain proteins and nucleic acids. When the human body is deficient in zinc for 48 hours, it causes protein synthesis disorders, interferes with cell division, and causes mental decline. Foods containing high zinc include fish, meat, eggs and nuts. Calcium, for the brain, can inhibit the abnormal excitation of the brain and cause the brain to enter normal working and living conditions. Conversely, the brain will cause emotional instability under the calcium deficiency level, causing fatigue of the brain and severe calcium deficiency. Increased dissolution of bone calcium, causing calcium deposition on brain cells and their peripheral nerves, disrupting brain function and causing dementia. Calcium-rich foods include milk, beans, sesame paste, shrimp skin, fish, etc. Calcium deficiency can also cause aluminum in the brain. In the cell, the content of aluminum in some brain regions of patients with Alzheimer's disease is 10 to 30 times higher than that of normal people. Aluminum is a strong cross-linking agent that directly destroys nerves. Inherent genetic material, causing cell shrinkage, can lead to inter-neural connection breakage, resulting in memory damage. Foods containing more selenium include mutton, turkey leg, chicken liver, milk powder, scutellaria, herring, squid and other meat foods. Keji contains more than 30 mg; cabbage, onion, seafood is rich in content and is edible.
5. Free radicals are the bane of dementia. Modern science proves that the antioxidants of effective substances that eliminate free radicals are mainly vitamin C, vitamin E, -carrot and selenium. Enzymes are enzymes that promote a series of chemical reactions in the human body. Proteins and enzymes will be destroyed by heat. In order to increase the enzymes in the body, it is best to eat more raw foods or eat them after cooking. The enzyme that delays the decline of brain power is peroxidase. The raw materials are abundant in broccoli and fresh peas. The lack of histidine in the tender stems of Aster can affect learning and memory. This wonderful natural resource can be found in fresh fruits, especially apples.
Foods containing more vitamin C include: kale, cauliflower (cauliflower), rapeseed, watercress, red cabbage, cabbage, cabbage, leeks, leeks, lettuce leaves, rapeseed, scallions, leeks, lettuce, spinach, etc. Each 100 grams contains ascorbic acid (vitamin C) more than 30mg; in addition, jujube, cantaloupe, grapefruit juice, oranges and other fruits or dried fruits are also rich in content, available for selection, foods containing more vitamin E: yuba, soybeans Powder, dried bean curd, vegetarian chicken, soy beans, bean curd and other bean products, as well as almonds, raw malt, sunflower oil and other foods.
Foods containing more -carotene; watercress, winter cold, kale, spinach, leeks, celery (leaf), leeks, cabbage, black scallion, leeks, sage, lettuce, scoop white, leeks , Jinyecai (daylily), etc., contains more than 1000mg of carotene per 100g; chicken liver, foie gras, pig liver vitamin A content exceeds 4900mg per 100g, in addition, carrots, sweet potatoes and other vegetable foods are also many.
In short, the key to the prevention of this disease lies in the application of various methods, including drugs, nursing, psychology, physical therapy, etc., to delay the aging process of the entire body, and at the same time, actively prevent various infectious diseases and trauma, treat various chronic physical diseases, and constantly Improve health and quality of life.
Complication
Menopause and complications of Alzheimer's disease syndrome Complications dementia
This disease is caused by dementia, so it is easy to suffer from various chronic physical diseases and secondary systemic infections or failures.
Symptom
Menopause and Alzheimer's Syndrome Symptoms Common Symptoms Dementia Depression Psychology Illusion Orientation Dysfunction Dysfunction Menopause Restlessness Bulimia
The main clinical manifestation of this disease is cognitive impairment. It can be divided into two subtypes according to the onset of illness. The patients who started from the age of 65 are called early onset, and the onset is early and the symptoms deteriorate rapidly. The patients who started after 65 years old are called Late onset, late onset, symptoms slowly increase, with memory impairment as the main performance.
Dementia is characterized by mental retardation and changes in behavior and personality. It is a manifestation of brain dysfunction caused by physical or brain lesions, poisoning or mood disorders. Typical symptoms are memory, abstract thinking, orientation, etc. At the same time, it is accompanied by a decline in social activity.
Memory impairment
Most patients are concealed onset, and early are easily ignored by patients and their families. The main manifestation is the gradual memory disorder. The events that happen on the day cannot be memorized. The things that have just been done or not remembered, and the names of familiar people cannot be remembered. Forget dating, forget where valuables are placed, vocabulary is reduced, early recurrence of remorse is mainly due to impaired memory, and then the memory is also impaired, affecting daily life.
2. Cognitive impairment
It is a characteristic clinical manifestation of AD disease. Cognitive function is composed of sensory, sensory, thinking, attention, and memory activities. Intelligence is a complex and comprehensive mental activity function, which is closely related to the above four cognitive functions. Intelligence can be expressed as comprehension, computational power, analytical power, creativity, etc. Cognitive functions also include orientation, self-awareness, etc. Cognitive impairment is the abnormality of all aspects of the above functions.
The cognitive impairment of AD includes memory loss, aphasia, loss of recognition, directional calculation and judgment, etc.; personality, behavior, emotions can also change, master new knowledge, proficiency and social ability decline, and gradually increase over time, Gradually language dysfunction, unable to speak complete sentences, reduced spoken language, difficulty in finding words, naming obstacles, erroneous language problems, decreased conversation ability, impaired reading comprehension, but reading can be relatively reserved, and finally completely aphasia; computing power disorder Often miscalculated, paying the wrong money, and finally the simplest calculations can not; in severe cases, there is a visual orientation disorder, when the jacket is not stretched into the sleeve, the tablecloth can not align the corners of the tablecloth and the table corner, get lost Or do not recognize the door, can not draw the simplest geometry; will not use the most commonly used items such as chopsticks, spoons, etc., but still retain the muscle strength and coordination of exercise.
3. Concomitant mental disorders such as thinking, mood, and behavior
Often the reason for patients seeking medical treatment, mental symptoms include depression, emotional apathy or loss of control, restlessness, excitement and euphoria, less initiative, distraction, talking to themselves during the day or talking loudly, fear of being alone at home; Some patients have fragmentary delusions, hallucinations and attacking tendencies, and some suspect that their old spouses have an affair; delusions and quirky behaviors, such as suspecting that children steal his money, and hiding valuable things as treasures; Neglected eating or bulimia; most patients have insomnia or nighttime paralysis.
4. Checking
It can be found that the patient is fidgety, irritating, less moving, not trimming, poor personal hygiene, general vision, relatively complete vision, no pyramidal tract sign and sensory disturbance; gait is generally normal, small steps can occur in the later stage, balance disorder Etc., 5% of patients may have seizures and Parkinson's syndrome.
Examine
Menopause and Alzheimer's disease syndrome
1. Hormone level detection.
Detection of metabolites of 2.5-hydroxytryptamine.
2. CT examination
At the beginning of the onset and the CT scan of the brain is basically normal. After the disease is aggravated, CT shows atrophy of the cerebral cortex, enlargement of the ventricle, and atrophy of the sulcus.
3. EEG examination
At the early stage of the onset, the EEG is basically normal. As the disease progresses, the background EEG is a slow rhythm, and the disease progresses to the end. The EEG shows diffuse large slow waves.
4. Histopathological examination.
Diagnosis
Diagnostic diagnosis of menopause and Alzheimer's disease syndrome
According to the age of onset, slow mental retardation and personality changes, combined with laboratory tests, can be considered intrinsic, diagnosed according to brain pathology, clinical diagnosis can have a 10% misdiagnosis rate, mainly based on many advanced neurological activity scales (such as mini mental Tests of statescore, MMSS; National Institute of Neurological and Communicative Disorders and Stroke-AD and Related Dis-orders Associetion criteria, NINCDS-ADRDA).
However, it must be differentiated from Pick disease, arteriosclerotic psychosis, encephalopathy, senile psychosis, paralytic dementia.
