bubble_chart Overview

This is a group of primary degenerative brain diseases of unknown cause. They typically begin in old age or presenility, develop slowly and progressively, with dementia as the main manifestation. The pathological changes are mainly characterized by diffuse brain atrophy and neuronal degeneration. In the past, they were classified as presenile dementia and senile dementia based on the age of onset. Modern research tends to regard them as a single disease entity, commonly referred to as Alzheimer's disease. Those with onset in presenility often have a family history of the same disease, and the condition progresses more rapidly. In the elderly populations of developed countries, the prevalence of dementia is 4-6%, with the proportion increasing steadily with age. It is generally believed that the prevalence doubles every five years of age. More than half of these cases are Alzheimer's disease, which is more common in women than in men. Survey data from some regions of China are also close to this. With the extension of the average lifespan in China, this disease will become an important topic in geriatrics.

bubble_chart Etiology

In recent years, significant breakthroughs have been made in the study of the disease cause of this condition. Through the application of molecular genetics and linkage analysis methods, it has been discovered that this disease is a familial hereditary disorder. Among certain patients' family members, the risk of developing the same disease is higher than in the general population. Additionally, it has been found that the risk of Down syndrome is also increased, indicating a potential familial connection. The brains of individuals with both conditions exhibit identical neuropathological changes. The deposition of β-amyloid protein, the main component of senile plaques, is linked to the amyloid precursor protein gene located on the long arm of chromosome 21. This has been confirmed in early-onset cases. For delayed onset cases, an association has also been identified with the apolipoprotein E-4 (APOE4) genetic gene located on chromosome 19. Certain genes on chromosome 14 are also believed to be related to the disease development process, demonstrating a definitive hereditary connection.

Other hypotheses regarding the disease cause include: the acceleration of the normal aging process, the accumulation of neurotoxins such as aluminum or silicon in the brain; progressive failure of the immune system; weakened toxin-removing function of the body; and slow sexually transmitted disease infections, all of which may be related to the onset of this disease. The likelihood of developing the disease is higher among the elderly, those who are widowed, have low education levels, live alone, face economic hardship, or experience unstable living conditions. Psychosocial factors may serve as triggers for the onset of this group of diseases.

bubble_chart Pathological Changes

Pathological examination revealed atrophy of the cerebral cortex, flattened gyri, widened sulci, enlarged ventricles, and reduced weight. The atrophy was most pronounced in the temporal, parietal, prefrontal, and hippocampal regions, with more significant manifestations in early-onset cases. Histological examination showed widespread disappearance or degeneration of large neurons in the deep cortical layers, chromatolysis, shrunken nucleoli, reduced dendritic processes, and astrocytic proliferation. Characteristic senile plaques and neurofibrillary tangles were also observed. Senile plaques are argyrophilic tissue changes resembling dissipating ecchymoses, appearing round or irregular, with a core formed by amyloid deposits surrounded by degenerated astrocytes. The number of cortical senile plaques correlates with clinical symptoms. Many studies have found abnormal axons and dendrites within senile plaques. Neurofibrillary tangles are composed of paired helical filaments (PHF) or neurotubules, both representing amyloid degeneration of neural tissue, predominantly found in large neurons of the deep cortical layers. The presence of senile plaques and neurofibrillary tangles is not consistent; some elderly patients may exhibit numerous senile plaques but only a few neurofibrillary tangles. Generation and transformation studies showed that most neuropeptides, such as cholecystokinin, thyrotropin-releasing factor, and substance P, were within normal ranges, while acetylcholine, serotonin, and norepinephrine levels were decreased. The reduction in acetylcholine was most notable in the hippocampal region, whereas growth hormone levels were elevated.

bubble_chart Clinical Manifestations

The onset is often insidious, with symptoms appearing rapidly in a few patients due to physical illness, {|###|}fracture{|###|}, or mental stimulation. Memory impairment is often the first symptom of the disease, such as frequently losing items, forgetting promised tasks, or repetitive and verbose speech. Subsequently, intellectual decline becomes increasingly severe, manifesting as inability to recognize hunger or fullness, getting lost outside and unable to find one's way home, failing to recall family members' names, or even being unable to correctly answer one's own name, age, or marital status. Sometimes, memory decline leads to confabulation or fabrication; or suspicion of theft due to misplaced items; or delusions of infidelity due to intense jealousy. Such fragmentary delusions may gradually fade as dementia worsens. Patients' visuospatial orientation is often impaired early on, and they may fail to copy simple three-dimensional figures, as detected by neuropsychological tests. Some patients cannot use words correctly, fail to recognize their own image in a mirror, and may exhibit aphasia, agnosia, apraxia, autotopagnosia, and primitive reflexes like grasping and sucking.

Some patients primarily exhibit emotional disturbances early on, presenting with manic or depressive symptoms, which may be misdiagnosed as functional psychosis. As the condition gradually worsens, dementia symptoms become increasingly evident, leading to a confirmed diagnosis. Patients may also experience personality changes, loss of shame and moral judgment, neglect of personal hygiene, inability to care for themselves, and hoarding worthless items as treasures. By the {|###|}late stage (third stage){|###|}, they become bedridden, suffer from severe urinary incontinence, slurred speech, and incoherent language.

In some patients, psychiatric symptoms deteriorate sharply during the course of the disease, leading to confusion or {|###|}delirium{|###|} accompanied by illusions and hallucinations. This is often triggered by acute psychological trauma, environmental changes, or various physical illnesses, such as asymptomatic pneumonia, urinary tract infections, or {|###|}fracture{|###|} injuries. However, varying degrees of personality changes and intellectual deficits persist.

Physically, patients appear aged, with dry, wrinkled skin, pigmentation, gray hair, tooth loss, muscle atrophy, and diminished pain response. Other neurological examinations often show no significant positive {|###|}sign{|###|}. In the {|###|}advanced stage{|###|}, symptoms such as tremors, spasms, hemiplegia, and muscle rigidity may appear. Early EEG results may only show slowed alpha rhythms, while the {|###|}advanced stage{|###|} exhibits diffuse slow waves. CT scans may reveal cortical atrophy and enlargement of the third ventricle.

The disease progresses relentlessly, typically over an average of 5–10 years, with little chance of spontaneous recovery. Eventually, severe dementia develops, often leading to death due to secondary physical illnesses or exhaustion, such as {|###|}bedsore{|###|}, {|###|}fracture{|###|}, or pneumonia.

bubble_chart Treatment Measures

Currently, there are no specific therapeutic measures for the disease cause, so general life care and nursing are extremely important. Pay attention to the patient's diet, nutrition, and daily hygiene, and try to encourage the patient to manage their own daily life. Encourage the patient to engage in appropriate activities with Ginseng to slow down mental decline. Avoid letting the patient engage in potentially dangerous activities alone. For bedridden patients, strict precautions should be taken to prevent bedsore, secondary infections, and fracture, among other complications.

Medications used to improve cognitive function and promote brain metabolism include: meclofenoxate, γ-aminobutyric acid, Pyritinol, ribonucleic acid, hydergine (oxidized ergot alkaloid), huperzine A, and choline precursors such as deanol, as well as calcium channel blockers like flunarizine and nimodipine, which may be helpful. Generally, antipsychotic drugs are not needed for most patients. If the patient exhibits symptoms such as mental agitation, depression, behavioral disturbances, or is difficult to manage, small doses of neuroleptics, anxiolytics, or antidepressants may be administered. However, attention should be paid to side effects, and the medication should be discontinued promptly once symptoms improve.

bubble_chart Differentiation

The onset is slow, with gradually worsening dementia as the main clinical symptom. Although the progression of the condition may temporarily pause, it is irreversible. Apart from ruling out other possible causes of dementia based on medical history, physical examination, and laboratory tests, it is necessary to differentiate from the following diseases.

1. Other psychiatric disorders in the elderly Depressive symptoms are not uncommon in the early stages of old age. Patients may exhibit memory decline, difficulty thinking, slow responses, reduced reactions, and decreased movement, which can easily create a false impression of "dementia." However, depressive symptoms have a relatively acute onset, often with a clear boundary, and the patient's intelligence and personality remain intact before the illness. The main clinical manifestations are emotional depression. Careful examination may reveal that the patient's responses remain relevant, self-awareness is preserved, and there is a good response to antidepressants, with no residual personality or intellectual impairment. Toxic, symptomatic, reactive psychoses, and schizophrenia occurring in old age can be differentiated based on detailed medical history, careful physical examination, and psychiatric evaluation.

2. Other diseases presenting as dementia Many diseases can cause symptoms of dementia, such as pernicious anemia, neurosyphilis, frontal lobe tumors, normal pressure hydrocephalus, and other primary degenerative brain disorders leading to dementia, such as Pick's disease, Huntington's disease, and Parkinson's disease. Most of these conditions can be reversed if diagnosed and treated early. Clinically, differentiation requires a combination of medical history, physical examination, and laboratory tests. For the differentiation from psychosis due to cerebral arteriosclerosis, refer to the detailed description of multi-infarct dementia below.