bubble_chart Overview

Alzheimer's disease is a chronic degenerative brain disorder. Its cause remains unknown, characterized by distinctive neuropathological and neurochemical changes. It typically develops gradually, with onset possible in the presenile period, though incidence is higher in old age. Cases beginning before age 65 often have a family history of dementia, progress more rapidly, and exhibit marked temporal and parietal lobe damage, including symptoms like aphasia and apraxia, with more frequent pyramidal tract signs. AD can persist for 20 years: 9 years in the early or grade I stage, 5 years in the intermediate or grade II stage, and 6 years of deterioration, imposing a heavy burden and suffering on individuals, families, and society. Statistics indicate 2-4 million AD patients in the U.S. and 17-25 million globally. Large-scale surveys in China are lacking, but recent urban census results show AD prevalence surpassing vascular dementia. In Western countries, AD ranks as the fourth leading cause of death after heart disease, cancer, and stroke.

bubble_chart Etiology

The significant changes in the brains of AD patients manifest as generalized cerebral atrophy, particularly pronounced in regions associated with higher cognitive functions, such as the hippocampus and corresponding cortical areas. There is also ventricular enlargement and widening of the cerebral sulci. A dramatic and marked reduction or disappearance of neurons and synapses is observed in the central nervous system. Ganglion cells undergo widespread degeneration, exhibiting shrinkage, vacuolation, and lipid deposition, accompanied by characteristic diffuse senile plaques (SP), predominantly in the frontal lobe. These typically appear between the ages of 50-60 without obvious triggers, along with neurofibrillary tangles (NFT).

Features of SP:

1. Contains amyloid fibers, showing a positive reaction to amyloid;
2. Immunohistochemical tests confirm the presence of IgG in SP, which normally reacts with antiserum.

bubble_chart Type

Most scholars classify this disease into four types based on clinical symptoms:

1. Simple type: The most common, primarily characterized by the aforementioned dementia symptoms.
2. Depressive type: Often manifests as excessive concern about one's own body and low mood.
3. Manic-grandiose type or early-onset type (prsyophrenia): Initially characterized by lengthy speech, grandiosity, and emotional excitement, often accompanied by confabulation and exaggeration. However, in the advanced stage, it may shift to impoverished and repetitive content, eventually resulting in only monotonous and incomprehensible words.
4. Hallucinatory-delusional type: Paxa л bcknn noted that over half of the patients with this disease exhibit various delusions, the most common being delusions of loss secondary to memory deficits, followed by delusions of jealousy, hypochondria, influence, persecution, grandiosity, and litigation. Most delusions are unstable, impoverished in content, and fragmented, yet still somewhat close to reality.

bubble_chart Clinical Manifestations

The disease is more common in women than in men (approximately 1.5–2:1). It usually develops gradually, making it difficult to determine the onset. By the time dementia becomes apparent and medical attention is sought, it is often more than 1 to 2.5 years after the onset. Yang Desen's data indicate that 70.6% of cases have a disease duration of less than 5 years, while 29.4% last more than 5 years.

1. Intellectual decline: Initially, there is often an accelerated deterioration of aging, with symptoms such as slowed, sticky, and rigid thinking, increased self-centeredness, difficulty controlling emotions, poor concentration, verbosity, and carelessness in tasks. Within a few years, malignant forgetfulness emerges, progressing from occasional to frequent forgetfulness, from recent events to distant memories, and from details to the events themselves. Immediate recall is severely impaired, making it impossible to remember events that occurred hours or even minutes earlier, resulting in a shortened memory span. Eventually, it may become so severe that even one's name, birthday, and family members are completely forgotten, as if living in childhood, often accompanied by a decline in calculation ability.
   Alongside memory impairment, disorientation may also occur. For example, patients may not recognize the way home after going out or fail to find their hospital bed after using the toilet.
   Difficulty in association, reduced comprehension, and poor judgment. Initially, this manifests as a lack of planning and creativity in work, followed by an inability to complete even familiar tasks. For instance, a renowned chef may lose the ability to control cooking temperatures and seasoning, resulting in dishes that are either undercooked or burnt, too bland or too salty, rendering them inedible. In severe cases, patients may fail to understand others' speech, opening their mouths when told to undress or standing motionless when asked to extend their hands.
2. Behavioral changes: Behavior first becomes childish and clumsy, often involving futile activities, followed by aimless actions. Examples include rummaging through drawers, misplacing items, and bustling about without purpose; hoarding worthless items as treasures, fearing theft; neglecting personal hygiene, such as wearing dirty clothes or skipping morning漱口. Sometimes, irrational or disruptive behaviors affecting public order may occur. Others may exhibit increasingly fewer movements, sitting motionless in a corner like a wooden statue. In the advanced stage, patients become completely immobile, bedridden, incontinent, and entirely dependent on others for care, resembling a vegetative state. Statistics show that 60% of patients die within 6 months of hospitalization, and 80% die within 18 months, primarily due to secondary infections.
3. Emotional disturbances: Initially, emotions may become childish or exhibit childlike euphoria, with irritability. Later, facial expressions become blank, and emotions dull.
4. Focal symptoms: Occasionally, focal symptoms may appear during the course of the disease. For example, damage to the neocortex most commonly and earliest presents as anomic aphasia, though other forms of aphasia, as well as various apraxias, agnosias, and acalculias, may also occur. Ultimately, cognitive abilities may be entirely lost.
5. Changes in appearance: Patients with senile dementia often appear aged, with a frail and elderly demeanor, white hair, tooth loss, sunken mouth, and arcus senilis in the cornea. Pupillary light reflexes may occasionally be sluggish. Sensory organ function declines, physiological reflexes become迟钝, the body stoops, gait becomes unsteady and shuffling, weight loss occurs, muscles atrophy from disuse, involuntary head shaking, slurred speech, drooling, finger tremors, and difficulty in writing may also be observed.

bubble_chart Diagnosis

The diagnosis of AD must first recognize the clinical symptoms of AD, with a detailed inquiry into medical history, followed by a thorough mental status and neurological examination.

The diagnostic criteria established in China in 1993 are as follows: (1) Dementia confirmed by intelligence tests; (2) At least two cognitive impairments; (3) Progressive worsening of memory and cognitive impairments; (4) No disturbance of consciousness; (5) Onset between ages 40-90; (6) No other physical or brain diseases can explain the above conditions.

Supporting conditions: (1) Progressive worsening of aphasia, apraxia, or agnosia; (2) Impairments in daily life and behavior; (3) Similar cases in the family; (4) Normal cerebrospinal fluid, nonspecific changes in EEG, CT showing brain atrophy, and progressive worsening.

The pathological diagnostic indicators for AD are relatively clear: (1) <60歲痴呆者，腦活栓組織中應有大量SP(≧15個/10個低倍視野)和NFT；⑵> In individuals aged 70 or older with dementia, only SP (senile plaques) are found in brain tissue without NFT (neurofibrillary tangles), and SP must be abundant; (3) If only NFT is present in brain tissue, it only meets the diagnostic criteria for dementia pugilistica, not AD; (4) If neither SP nor NFT is found in the brain tissue of a dementia patient, other causes should be considered.

DSM-IV (1994) diagnostic criteria

WHO's ICD-10 (1992) diagnostic criteria

The criteria set by the American National Institute of Neurological Disorders and Stroke (NINDS) and the Alzheimer's Disease and Related Disorders Association (ADRDA) state that based on symptoms, scales, and neuroimaging findings, a diagnosis can only be made as "probable Alzheimer's disease," with confirmation relying on brain tissue biopsy. This is difficult for patients and families to accept in China, making early diagnosis of AD even more challenging.

Currently, the U.S. has adopted double-label immunohistochemistry to detect NFT and stereological techniques to quantify neuron numbers and tau levels. Some institutions in China are measuring phosphorylated neurofilament (PNF)/PHF values in cerebrospinal fluid.

Regardless, the clinical misdiagnosis rate for dementia remains high (>15%), especially in early diagnosis, which is particularly difficult. CT/MRI has diagnostic value, and positron emission tomography (PET) research and applications are gaining attention.

bubble_chart Treatment Measures

There is currently no definitive and highly effective or curative method. Medications for treating AD are mainly divided into two categories:

1. Enhancing the function of the cholinergic system in the brain, primarily through cholinesterase inhibitors and M-cholinergic receptor agonists.
2. Neuroprotective agents acting on the neurotransmission system to delay the degeneration of brain neurons. Theoretically, blocking the formation of β-amyloid protein (ABP), inhibiting ABP's neurotoxicity, and protecting or repairing neurons can achieve the goal of preventing and treating AD.

Currently, the U.S. FDA has approved only two drugs for treating AD: tacrine, approved in September 1993, and E-2020 (donepezil), approved in March 1997, both of which are cholinesterase inhibitors.

Others:

1. Aluminum chelating agents, such as deferoxamine, can reduce aluminum absorption and its concentration in brain tissue, with good tolerability. Some clinical and experimental evidence exists.
2. Nonsteroidal (NSAIDs) and steroidal anti-inflammatory drugs Yaodui have shown some alleviation of symptoms in certain patients and are considered one of the candidate treatment strategies.
3. The use of sex hormones: proponents believe that estrogen replacement therapy for postmenopausal elderly women may have some effect on dementia in elderly women.
4. Drugs that improve brain metabolism: such as ginkgo leaf extract, which can enhance neuronal metabolism and positively influence neurotransmitters; large doses of piracetam can slow the progression of AD and improve naming and memory recall.
5. Calcium channel blockers: such as nimodipine. Recent studies indicate that cellular calcium overload and imbalance in calcium homeostasis, caused by various factors, are the final common pathways leading to cell death.
6. Gene therapy: using recombinant technology to replace defective genes with normal ones to achieve a cure for genetic defects, though this is not yet feasible. Administering exogenous nerve growth factors can effectively prevent damage to the central cholinergic system and improve animal learning and memory. The first case report of using nerve growth factors to treat AD has been published; one month after intracerebral injection, improvements in serial word memory were observed, though other cognitive functions remained unchanged.
7. Chinese medicine and Chinese medicinals treatment: Historical records exist, generally focusing on the brain, heart, kidneys, and other zang - fu organs, as well as disease mechanisms involving qi, blood, phlegm, stasis, fire, and stagnation. In recent years, Japan has studied AD using Angelica and Peony Powder, Uncaria Powder, and Coptis Detoxification Decoction from perspectives of stagnation, wind, heat, and toxins, suggesting some efficacy in improving learning and memory in AD.
8. Acupuncture and moxibustion therapy: Currently under exploration. Scalp acupuncture targets bilateral language areas and vertigo-auditory areas; ear acupuncture targets the heart, brain, subcortex, and endocrine points; body acupuncture targets Fenglong (ST40), Jian Shi (PC5), Dazhui (GV14), Shenshu (BL23), philtrum, Neiguan (PC6), and Fengchi (GB20), generally emphasizing point selection based on pattern identification.