Parkinson's disease dementia
Introduction
Introduction to Parkinson's disease dementia Parkinson's disease (PD), paralysisangitas, is a chronic neurodegenerative disease in middle-aged and elderly people. This was first reported by Parkinson in 1817. The disease belongs to the primary central nervous system degenerative disease, which can be scattered in the onset or family genetic disease. It is a slowly occurring selective loss of dopaminergic neurons in the substantia nigra and a significant reduction in striatal dopamine levels, leading to a series of symptoms of the extrapyramidal system, with reduced exercise, muscle rigidity, tremors and postural adjustment disorders. Clinical manifestations of the disease. basic knowledge The proportion of illness: 20% (incidence rate is 20% in elderly patients) Susceptible people: The disease is mostly in middle-aged and elderly people, and the age of onset is 55-61 years old. Mode of infection: non-infectious Complications: pneumonia, urinary tract infection, depression
Cause
Causes of Parkinson's disease dementia
Genetic factors (25%):
Some cases (10% to 15%) are autosomal dominant inheritance patterns, but despite the discovery of genetic research, there is still much controversy in the academic world, which may be related to polygenic inheritance. It is still difficult to determine and needs further study.
Loss of free radical damage and oxidative phosphorylation (20%):
At present, experiments have shown that the free radicals in the Parkinson's patients group are significantly higher than the control group, and the mitochondrial complex 1 oxidative phosphorylation defects, which are related to the damage caused by mitochondrial DNA and other macromolecules.
Environmental risk factors (15%):
Clinical and experimental studies have shown that a substance poisoning called 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) is associated with the pathogenesis of Parkinson's disease. Parkinson's disease has been made with NPTP. The model was studied experimentally.
In conclusion, studies on the pathogenesis of Parkinson's disease, although currently with 65% to 70% of the substantia nigra dopamine neurons degeneration, reduction, loss, resulting in a decrease in the striatal dopamine transmitter, making the striatum dopamine and Acetylcholine (ACh) is imbalanced and mainly affected, but studies have also confirmed that other neurotransmitters in the brain such as norepinephrine (NE) serotonin (5-HT) and gamma-aminobutyric acid (GABA) are also involved. The pathogenesis process.
Pathogenesis
Since the etiology of Parkinson's disease has not been known so far, the pathogenesis is not well understood. It is currently believed that the dopaminergic neurons in the substantia nigra are degenerated, reduced, and lost, resulting in a decrease in DA transmitters acting on the striatum, resulting in striatum. The balance of DA and Ach is dysfunctional. Biochemical studies have found that the DA content in the striatum of PD patients is significantly reduced. Further studies have shown that patients with tremor paralysis and DA and Ach imbalance between neurotransmitters, cholinergic activity predominates. Related, neuropathologists believe that the changes are mainly in the substantia nigra pars compacta and pons erythema, they found that the substantia nigra and blue plaques become lighter and lighter, and the pigmented neurons are degenerated, reduced, lost, and visible under the microscope. Free pigment granules and astrocytic hyperplasia, with characteristic diagnostic significance, are seen in residual pigmented neurons. Intracellular inclusion bodies, Lewy bodies, are characterized by eosinophils in nerve cells. Around the center, surrounded by a pale halo-like structure, studies have shown that Lewy body inclusions are caused by abnormal cytoskeletal proteins, Ubiquitin and lattice microfilaments. Protein and other immunocytochemical staining positive substances, especially ubiquitin protein staining positive nerve filaments are not only found in the substantia nigra, but also in hippocampal CA2, zone 3, vagus dorsal nucleus, Meynert basal ganglia and amygdala.
In recent years, studies have confirmed that dopamine accumulation in the cytoplasm can lead to neuronal death. The vesicular monoamine transporter has protective effects on dopamine neurons. The researchers used experimental animal models and cell culture, protein electrophoresis techniques for experimental research. It was confirmed that the neurotoxic substance MPP has a strong affinity with the vesicle monoamine transporter in the presynaptic membrane, which affects the storage of dopamine in synaptic vesicles, resulting in increased dopamine in the synaptosome cytoplasm, and dopamine through self-oxidation. Produces a large amount of free radicals and terpenoids, leading to degeneration and even death of dopaminergic neurons. However, if dopamine binds to vesicular monoamine transporter and enters acidic secretory vesicles, it can avoid auto-oxidation of dopamine. Play an important role in the neuroprotective mechanism.
The researchers also injected intraperitoneal injections of a certain dose of risperidone to cause symptoms of Parkinson's disease, such as skeletal muscle stiffness and bradykinesia, which is due to inhibition of vesicular monoamine transporters by risepine. The activities and functions of the vesicle monoamine transporter are inhibited from the pathogenesis of Parkinson's disease. To further confirm the above findings, the laboratory cloned vesicle monoamine transporter gene is transcribed into In the fibroblast CHO, it was found that the fibroblast CHO expressing the vesicle monoamine transporter can resist the toxicity of the neurotoxic substance MPP, and the fibroblast CHO cytoplasm expressing the vesicle monoamine transporter after the neuronal dopamine The endogenous dopamine accumulation is rare, and the cell death rate is significantly lower than that of the fibroblast CHO of the untranscribed vesicle monoamine transporter gene. These experimental results further confirm that the accumulation of dopamine in the cytoplasm is positively correlated with neuronal mortality. The accumulation of dopamine in the cytoplasm can lead to neuronal death, possibly related to the pathogenesis of Parkinson's disease, and vesicular monoamine transporter Its function is related to the accumulation of dopamine in neurons, which has protective effects on dopamine neurons. This study provides a new theoretical basis for the treatment of Parkinson's disease, and questions the traditional levodopa treatment of Parkinson's disease.
Prevention
Parkinson's disease dementia prevention
At present, the etiology and pathogenesis of Parkinson's syndrome are not yet clear. Medical precautions against unexplained diseases are lacking, but taking antipsychotic drugs can also cause this disease. If it is caused by this cause, such patients It can be prevented, mainly because taking such drugs must be prescribed by a doctor in a regular hospital. When taking the medicine, it should be closely observed. Once there is a tendency, it will be stopped immediately and go to the hospital for a follow-up visit.
Although the cause of Parkinson's disease is not fully understood, many studies have shown that it may be related to environmental toxins. Some studies have shown that compared with people who have never used pesticides or herbicides at home or in the yard. People who use these two drugs for a lifetime less than 30 days in their lifetime will have a 40% increase in the risk of Parkinson's disease; if they use more than 160 days in a lifetime, they will suffer from Parkinson's disease. The chance is increased to 70%, especially for people with Parkinson's disease in the family. If someone has a Parkinson's disease in their immediate family, then the chance of developing Parkinson's disease is greater, so Special care should be taken to avoid exposure to environmental hazards such as pesticides, pesticides, heavy metal manganese, and people with Parkinson's disease in their relatives should avoid welding.
Parkinson's disease diet principles and requirements:
1 limit the protein intake throughout the day, 0.8g per kilogram of body weight is appropriate, Parkinson's symptoms are relieved after sleep, protein distribution throughout the day should be less during the day, the amount of dinner increased.
2 The right amount of carbohydrates increased, 60% to 65% is beneficial.
3 Supply sufficient water to supplement water consumption and reduce side effects.
4 suitable for adding vegetables, fruits and honey.
5 Avoid irritating condiments and food, no smoking.
6 Nutritional therapy only has an auxiliary effect. In addition, when patients with Parkinson's disease choose diet, it should be considered that elderly patients are often accompanied by atherosclerosis, cardiovascular and cerebrovascular diseases, diabetes, etc., should be combined with the characteristics of this disease and the elderly, Appropriate total calories, normal adult 24h basal metabolism about 5857.6 ~ 7531.2kJ (1400 ~ 1800kcal), bedridden patients generally need to supply heat 6276 ~ 8368kJ (1500 ~ 2000kcal), patients who get out of bed generally need to supply heat 8368 ~ 9623.2 kJ (20002300kcal), a mild patient who is still engaged in manual labor, needs to supply 1004112552kJ (24003000kcal) of calories. The above data can be used as a reference when choosing a diet for a specific patient.
Parkinson's disease characterized by hand-foot vibration is due to the reduction of dopamine in the human brain. The study found that calcium intake through food can promote the synthesis of dopamine in the brain, so you should eat more calcium-rich foods, such as: shrimp, Kelp, seaweed, soy milk, soy products, milk, eggs, etc., have a good effect on the prevention of Parkinson's disease. In short, a pleasant meal and a variety of dietary combinations have a good effect on the prevention of Parkinson's disease, therefore, a day's diet food Should be varied, including cereals, vegetables, fruits, beans, meat, etc., according to the determination, eat 300 ~ 500g of cereals a day, you can get enough carbohydrates, protein, dietary fiber and vitamin B and other nutrients; Eat 400g of vegetables, 1 or 2 medium-sized fruits, from which you can get vitamins A, B, C, E and a variety of minerals and dietary fiber.
Foreign studies have shown that eating more vitamin-rich antioxidant foods can reduce the risk of Parkinson's disease. Proper tea, coffee and other caffeinated drinks also have a role in preventing Parkinson's disease. Foreign studies have found that drinking coffee every day. 1 to 2 cups can reduce the incidence of Parkinson's disease by 50%; if you drink 3 to 4 cups of coffee a day, the chance of getting Parkinson's disease is only 1/5 of that of normal people. The caffeine contained in caffeine drinks can be The sensitivity of the neurotransmitter in the brain is increased, so that the symptoms of muscle stiffness of Parkinson's disease are not likely to occur in behavior or movement.
Complication
Parkinson's disease dementia complications Complications, pneumonia, urinary tract infection, depression
The disease is a chronic progressive disease. The quality of life of patients is degraded due to motor function and mental disorders. If it is developed to dementia, it is more serious. If it is not treated in time, the patient's survival time is obviously shortened. Physical illnesses and secondary systemic infections or failures, such as pneumonia, urinary tract infections and other complications, about a quarter of Parkinson's patients with excessive fear of disease with depressive symptoms, women with depression may have suicide attempts.
Symptom
Symptoms of Parkinson's disease dementia Common symptoms Mask face ability decline gaze stagnation Cognitive dysfunction drooling mouth unclear panic gait hand tremor tension hand movement memory disorder
The disease is mostly caused by middle-aged and elderly people. The age of onset is mostly 55-61 years old, and the course of disease is slowly progressing.
1. Neurological symptoms and signs
(1) bradykinesia and akinesia are one of the common symptoms of PD. The onset is slow, mostly starting from a single limb or one limb. It is characterized by reduced movement and slow movement, and the limb is awkward and inflexible. Difficulty in movement, reduced coordination, affecting daily life, such as eating chopsticks; writing can be slow, the word is written smaller (called "lower case"); standing after standing for a long time, difficult to get up in bed, difficult to walk The upper limb synergy swing is reduced, and the faster and faster, the gait is gait, the forward stop is in the forward gait, the turning is not flexible or the turning action is decomposed. In the early stage, there is no language barrier, and the swallowing activity is not affected. Progress gradually became unclear, drooling, worsening of the condition, unclear speech, and dysphagia.
(2) Muscle rigidity, rigid posture abnormality and posture reflex disorder PD is also a common symptom, which is different from the increase of spastic muscle tension in pyramidal lesions. PD is an increase in extrapyramidal muscle tension, and both flexor and extensor muscles are violated. The muscle rigidity of PD is rigid, which is due to the persistent muscle extensor to increase the extensor and flexor muscle tension, so that the muscle stiffness can not be relaxed, the clinical manifestations are reduced, the movement is slow, due to the tension and uncoordinated tension and extension muscles, Examination showed that the muscle tension increased when the limbs were passively active, showing a gear-like impedance. The passive limbs showed lead tube-like rigidity, and the cheek muscles caused the facial expression to decrease, and the dull, unique mask face, resulting in muscle rigidity. Poor posture and posture reflex disorder, severe muscle rigidity makes the head lean forward slightly, the trunk flexes, the forearm adducts, the elbow flexes, causing the body to lose its normal upright posture, showing a forward leaning posture, becoming a PD-specific posture, walking It can be seen that the gait is flustered, the position is unstable, and the action is stabbed in severe cases.
(3) Tremor is also one of the three main features of PD, the most common, about one-third of patients with this as the first symptom, about 70% to 80% of patients have this symptom, tremor is active muscle group and antagonist muscle Uncoordinated group contraction leads to alternating contraction, causing limbs to have rhythmic tremors of 4-6 times/s. This symptom occurs slowly in clinical practice, starting from a single limb or one limb, and the distal extremity, especially the tremor of the hand. The most characteristic, it is opposite to the intentional tremor of ataxia, mostly in the quiet, called static tremor, finger tremor is obvious, is "skull-like" or "bead-like", in active random movements If the tremor is reduced or disappeared when taking the item, the tremor disappears during sleep, and the tremor is aggravated when the emotion is excited. Under normal circumstances, the onset begins with the tremor of the upper limb of one side, and the disease progresses to the lower limb and the contralateral limb, and the condition is aggravated. It can also involve tremors in the lower jaw, lips, tongue and head.
(4) Other symptoms and signs: PD patients have no subjective sensory abnormalities, but some patients may develop tonic muscle pain, such as shoulder and back pain, tingling and other discomfort, a small number of PD patients can see lower limbs, especially calf muscles Pain discomfort, mostly in the quiet or sleep, calf muscles creepy pain accompanied by irregular calf activity, showing restless leg syndrome, affecting sleep and rest.
PD patients with sputum reflexes are not tired, occasionally sputum reflexes are active and hyperthyroidism. When the muscle rigidity is severe, sputum reflexes are difficult to lead, but there is no pathological reflex. Once pathological signs are elicited, Parkinson's superposition syndrome should be considered, such as multi-system atrophy. Or considering secondary Parkinson's syndrome, multiple lacunar infarction can be seen in the presence of pyramidal tract signs and extrapyramidal signs, should be noted.
Autonomic dysfunction is also a common symptom of PD patients, clinical manifestations of hyperhidrosis, facial flushing, salivation, low skin temperature, intractable constipation and bladder emptying, and some patients with excessive sebum in the face or seborrheic dermatitis.
2. Mental and psychological symptoms
Attention deficit is a fairly common symptom in PD patients. It can be accompanied by decreased movement, slow speech, low mood, etc. Some patients have distracted attention, physiological illusions and even spatial perception.
A small number of patients have reduced active activities, personality changes, euphoria, naive behavior, unsociable character, timidity, wilting, hesitation, suspiciousness, irritability, self-centeredness, etc., reluctance to participate in social activities, and rarely visit relatives and friends. Depression and anxiety are mostly caused by mental disorders after illness, and 2% of patients can develop into depression and anxiety.
Illusory hearing, victim delusions and suspected delusions, association barriers are rare, and some are secondary to the embarrassing state of consciousness.
Depressed female patients are more common, manifested as slow response, depression, anxiety, severe suicide attempts, depression related to neuropathy, slow response, depression, anxiety, suicide attempts are often the main psychiatric treatment The reason, depression can also be the first symptom of this disease, more common in women.
PD patients with cognitive dysfunction, inattention, memory impairment is also associated with slow movements, depression, depression and other psychological disorders. If these patients are given sufficient time, their memory, computational power and orientation are still normal. However, about 15% to 20% of PD patients develop into comprehensive cognitive impairment, intelligent decline, clinical memory loss, computational power, orientation and judgment loss to develop into dementia. As the disease progresses, the intelligence gradually decreases, showing the cortex. Dementia characteristics.
Examine
Examination of Parkinson's disease dementia
1. The characteristics of Parkinson's disease laboratory diagnosis are not high.
2. Although the cerebrospinal fluid has been reported to be reduced in the content of dopamine metabolites high vanillic acid and serotonin 5-hydroxyindole acetic acid, it is not practical.
3. EEG examination showed no characteristic changes despite occasional slow wave changes.
4. Imaging: Head CT, MRI can be seen in a few cases of Parkinson's case, general brain atrophy, but no focal changes, MRI is very important in the differential diagnosis of Parkinson's disease syndrome, such as vascular disease Parkinson's syndrome There are multiple lacunar infarctions and infarct softening lesions in the basal ganglia. No single-photon radionuclide scanning (SPECT) is seen. The positron emission tomography (PET) 18-fluoro-bara (18F-dopa) is visible. Body area intake is reduced.
Diagnosis
Diagnosis and differentiation of Parkinson's disease dementia
Diagnostic criteria
The disease is slowly progressing, increasing year by year, affecting the entire social function, and finally leading to dementia, which is caused by physical illness or concurrent infection.
1. Middle-aged and elderly people have a slow onset and a chronic course.
2. Psychiatric symptoms appear after neurological symptoms.
3. The nervous system has three main characteristics - reduced movement and slowness, muscle rigidity, static tremor, nerve examination without pyramidal tract sign, secondary diagnosis of Parkinson's syndrome can be diagnosed.
4. In severe cases, dementia occurs.
Differential diagnosis
1. Parkinson's syndrome after encephalitis: occurs at any age, mainly history of encephalitis, after exercise can not be - tonic syndrome, sports awkward, myotonia, tremor, but static tremor is rare, as early as 1920 After the occurrence of "sleeping encephalitis" in Europe, there are cases all over the world. The cause of the disease is unknown. It is only from clinical, epidemiological and pathological findings that viral encephalitis is the main disease with brain stem and midbrain substantia nigra damage. Main, nerve cell necrosis, glial cell hyperplasia, glial nodules, clinical manifestations of Parkinson's syndrome with paroxysmal eye movement crisis, that is, paroxysmal eyeball fixation in any direction, each episode for a few minutes or even tens of minutes For symptomatic treatment, amantadine and trihexyphenidyl can be used, and dopamine preparations have poor efficacy.
2. Guam Parkinson-Dementia Syndrome: This disease is a disease that occurred in Guam in the western Pacific after the 1940s. It is more common in middle-aged people. It usually begins with Parkinson's syndrome accompanied by dementia. The emergence of amyotrophic lateral sclerosis, a few may also appear after amyotrophic lateral sclerosis, Parkinson's syndrome and dementia, pathological findings of general brain atrophy, substantia nigra and blue spot lightening, neurofibrillary tangles seen in In the substantia nigra, hippocampus, amygdala and neocortical neurons, senile plaques and Lewy bodies were not observed. Epidemiological studies suggest that exogenous environmental factors may cause disease, which may be related to the consumption of cycads. In recent years, it has proposed regional and soil chemical elements. Related, has not been finalized.
3. Drug-induced Parkinson's syndrome: mainly found in antipsychotic drugs, such as phenothiazines, perphenazine, fluphenazine, butyrylbenzene, haloperidol, and antihypertensive drugs, reserpine and calcium antagonists Lizin, flunarizine, etc.; long-term use of blocking dopamine D2 receptor can also induce the disease, the clinical manifestations of delayed dyskinesia, mostly with exercise reduction, slow, muscle rigidity as the main symptoms, static The tremor is rare, and the cause is clear. Most of the patients can relieve and recover after stopping the drug.
4. Vascular Parkinson's syndrome: more common in middle-aged and elderly people with hypertension, arteriosclerosis and diabetes, such as cerebrovascular disease risk factors, the main pathological features are basal striatum, internal capsule, thalamus, semi-oval center And laminar infarction or small infarction lesions such as pons, the clinical manifestations of most patients have a transient ischemic attack (TIA) or a history of small stroke episodes, pyramidal and extrapyramidal symptoms occur or occur sequentially, limb weakness, Exercise is reduced, slow, muscle rigidity or stiffness, multiple lower limbs are heavy, showing "small step gait", static tremor is rare, and more often accompanied by lower limb weakness, bilateral or unilateral pyramidal tract signs, pathological reflex positive Some cases have pseudobulbaric palsy, dysphagia, eventually personality changes, strong crying, cognitive impairment, dementia, etc., the course of the disease progressed stepwise, CT, MRI visible bottom section, striatum, internal Multiple cystic infarction or small infarction, such as sac, mainly for the treatment of primary cerebrovascular diseases, strengthening nursing, symptomatic treatment, using blood circulation and removing blood stasis, nerve cell activator, it is worth noting that it is left-handed No positive effect of levodopa.
5. Progressive supranuclear palsy (PSP): also a middle-aged and elderly central nervous system degenerative disease, the age of onset is 50-77 (64) years old, the lesions are mainly in the substantia nigra and blue spot, the midbrain nucleus, dentate nucleus and pale Ball, etc., slow onset, early appearance of extrapyramidal symptoms, decreased exercise, slow, static tremor is rare, muscle stiffness is obvious, posture balance disorder is one of the clinical findings, that is, the back muscles of the back muscles are erect and stretched It is easy to fall backwards, and Parkinson's disease is leaning forward, flexion, and anterior posture. Another clinical feature is supranuclear ocular paralysis, that is, the eyeball is up and down, the lower eye can not be observed, and the disease progresses slowly and cognitive impairment occurs. Depending on the spatial skills damage, the late development of dementia, the course of 3 to 12 (6 or 7) years, more than the lung infection, early levodopa preparations have a certain effect, long-term use is not effective and prone to orthostatic hypotension, recently proposed Free radicals, antioxidant treatment, the effect remains to be seen.
6. Multiple System Atrophy (MSA): MSA is a group of central nervous system degenerative diseases that occur in the middle-aged and elderly people aged 40-60 years. The onset of the onset is slow, first proposed by Adams (1961), including striatum substantia nigra , Shy-Drager syndrome, oligocytic-ponsius-cerebellar atrophy (OPCA) and amyotrophic lateral sclerosis (ALS), recent pathological studies have found that the above lesions are different, but the pathological changes are quite consistent, namely ubiquitin Staining positive glial cell inclusion bodies, nerve cell inclusion bodies and neurofilaments.
Its clinical symptoms are:
(1) Extrapyramidal sign: reduced movement, myotonia syndrome, but no resting tremor (striatum substantia nigra).
(2) orthostatic hypotension with spinal cord, autonomic dysfunction: impotence, bladder disorders, etc. (Shy-Drager syndrome).
(3) olive body - pons - cerebellar atrophy (OPCA): clinical features are extrapyramidal signs, pyramidal tract signs and cerebellar ataxia.
(4) Parkinson's syndrome symptoms complicated by spinal cord anterior horn lesions, hand muscle atrophy, amyotrophic lateral sclerosis symptoms.
Due to the slow onset of the disease, the above four symptoms do not occur at the same time, often appear one after another, clinically have two to diagnose MSA, and sometimes only one group of syndromes can also make a separate diagnosis such as OPCA or Shy-Drager Syndrome, etc.
Laboratory-assisted examinations help clinical diagnosis:
1 position vertical position blood pressure difference 40mmHg can diagnose orthostatic hypotension;
2 in the striatum substantia nigra degeneration, head MRI visible lateral fissure widening, nucleus atrophy and lateral ventricle enlargement and other brain atrophy;
3OPCA, MRI especially sagittal position can clearly show the bridge pool widening, pons and olives and cerebellar atrophy;
4 EMG can confirm Parkinson's syndrome with amyotrophic lateral sclerosis.
7. Identification with functional psychosis: early symptoms of mental symptoms are easily misdiagnosed, detailed physical examination can find evidence, mental symptoms often have organic damage color, such as consciousness, personality, memory, intelligent obstacles, should also pay attention to function Sexual psychosis presents with symptoms of pseudo Parkinson's disease in the treatment of antipsychotics.
8. Other brain degenerative diseases: from the medical history, neurological diseases and signs (triad) combined with "mask face", panic gait " mud pill" action to identify.
