I. Overview.
Alzheimer’s disease (AD), is a chronic degenerative brain disease. Clinical manifestations include progressive distant and near-term memory impairment, loss of analytical judgment, mood changes, behavioral disorders, and even blurred consciousness.
Its etiology is still unknown, and it has characteristic neuropathological and neurochemical changes, often with a gradual onset, which can occur in the early years of life, but with a higher incidence in old age. The type with onset before age 65 often has a family history of dementia and progresses more rapidly, with significant temporal and parietal lobe damage, including aphasia and dysfunction, and more symptoms in the pyramidal system. those with onset after age 65 progress more slowly, with extensive higher cortical dysfunction (i.e., memory impairment) as the main feature, and the characteristic brain pathology is a significant reduction in the number of neurons.
AD can last up to 20 years, 9 years in the early stage, 5 years in the middle stage and 6 years in the deterioration, causing deep burden and suffering to individuals, families and nerves. According to statistics: 2-4 million AD patients in the United States and 17-25 million worldwide. In Western countries, AD is the fourth leading disease causing death after heart disease, tumor and stroke.
To date, there is no effective anti-dementia drug therapy, and it is primarily a clinical care issue. The main challenges in the current research for the treatment of AD are: 1. the unknown causes and nature of AD; 2. the limitations of clinical diagnostic indicators; and 3. the lack of practical pathological staging indicators.
Note the distinction with senile dementia, which is not the same concept. There are four types of senile dementia: 1) senile dementia; 2) vascular dementia (Vascular Dementia VD), including multiple infarct dementia (Multl-infarct Dementia, MD); 3) mixed dementia; 4) dementia in the elderly caused by systemic diseases.
Etiology
The etiology is unknown. In recent years, a large number of foreign studies have focused on genetics, immunology, viral infections, neurotransmitters and neuroendocrine, etc., indicating that many factors are related to the pathogenesis and etiology of the disease.
1, genetic factors: AD has family aggregation, 40% of patients have a positive family history, autosomal dominant and polygenic inheritance, some people proposed genetic theory (or genetic theory), that, like Down syndrome, there are amyloidogenic genes on the 21st chromosome pair. Family history of late-onset AD has shown that the risk of late-onset AD is eight times higher in those with two apoE4 genes than in those with two apoE3, and lower in those with the apoE2 allele. It has been pointed out (Corder) that up to 75% of patients with late-onset AD are related to apoE to some extent.
2.Environmental factors
(1) Aluminum accumulation: Aluminum concentration in some brain areas of AD can be 10-30 times that of normal brain, and there are aluminum deposits in the core of senile plaques (SP). Aluminum is selectively distributed in the nerves containing neurofibrillary tangles (NFT), and aluminum affects gene expression after binding to chromosomes in the nucleus, and aluminum is also involved in the formation of age spots and neurofibrillary tangles. Therefore, some scholars proposed the “aluminum poisoning theory”.
(2) Viral infections: Many viral infectious diseases have been found to be morphologically similar to AD with structural changes of neurofibrillary tangles and senile plaques. For example, sheep itch (Scapie).Kwru disease Creutzfeldt-Jacob disease (C-J disease), etc.. All of them have symptoms of dementia in their clinical manifestations.
(3) Immune system dysfunction: AD prevalence is significantly higher in the elderly with advancing age (age increase), and increasing age is associated with immune system decline and increased autoimmune diseases.
(4) Neurotransmitter theory: Neuropharmacological studies of AD disease have confirmed that patients with AD have reduced acetylcholine transferase activity in the cerebral cortex and hippocampus, which directly affects the synthesis of acetylcholine and the function of the cholinergic system as well as reduced 5-HT and P substances.
(5) Normal aging: neurogenic fiber tangles and senile plaques can also be seen in normal human brain tissue, but the number is small, but these damages exceed a certain “threshold” level in AD.
(6) Estrogen action: Women who take estrogen for a long time are at low risk of AD, and studies have shown that estrogen protects cholinergic neurons.
In conclusion, among the complex etiological studies of AD, the two are clear: age-related changes and genetic factors. The presence of numerous neurofibrillary tangles (NFT) and senile plaques (SP) is characteristic.
III. Clinical manifestations.
The disease is more common in women than in men (about 1.5-2:1). It is difficult to determine the stage of the disease because of its slow onset, and when dementia is obvious, it is often more than 1 to 2.5 years after the onset.
1. Mental decline: Initially, the deterioration is often accelerated by aging, and there is a short-term delay in thinking, memory loss, and orientation disorder. For example, after going out, do not know the route home; after going to the toilet, can not find the bed they slept in.
Difficulties in association, reduced comprehension, and poor judgment.
2. Behavioral changes: Behavior may be childish and clumsy, often performing ineffective work, and then purposeless work may occur. For example, they may rummage through cupboards, put things in a messy way, be busy and do not know what to do; they love to hide waste and regard it as a treasure for fear of theft; they do not pay attention to personal hygiene habits, do not wash dirty clothes, do not rinse in the morning, and sometimes appear to act against reason and obstruct public order, affecting the security. There is also less and less movement, sitting in a corner, dull as a wooden chicken.
3, emotional disorders at first, the emotions can be more childish, or child-like euphoria, emotional irritability. Subsequently, the expression is dull, emotional retardation.
4, focal symptoms in the course of the disease, may occasionally appear focal symptoms. For example, the earliest and most frequent damage to the neocortical area is named aphasia, but there may also be other forms of aphasia, as well as a variety of loss of use, loss of recognition, loss of arithmetic, and eventually the cognitive ability may be completely lost.
5, appearance changes: external appearance of aging, often appear old, full of white hair, teeth fall mouth deflated, corneal with age ring. Pupil response to light is occasionally dull.
6. Laboratory tests are mostly unremarkable. EEG shows non-specific diffuse slow waves, slowed alpha wave rhythm and low amplitude. CT scan or MRI often shows different degrees of ventricular enlargement, cortical atrophy and widening of the cerebral sulcus.
Most scholars classify the disease into four types according to clinical symptoms: ① simple type: the most common, with the above-mentioned dementia symptoms. ②Depression: It often manifests as excessive concern for one’s body and depressed mood. ③Mania – exaggerated type or early type: speech is initially lengthy, boastful and emotionally excited, often accompanied by fiction and exaggeration, but in the late stage it may turn into content poverty and repetition, and eventually only monotonous and puzzling single words can be spoken. The most common delusions are delusions of loss secondary to memory loss, followed by delusions of jealousy, suspicion, influence, victimization, exaggeration, and litigation, etc. Most delusions are irregular, poor in content, and fragmentary, but still close to reality.