Definition and Overview
Alzheimer's disease is a degenerative brain disease in which nerve cells gradually disappear due to abnormal accumulation of amyloid beta and hyperphosphorylated tau protein in the brain. It begins slowly with a decline in recent memory and progresses to impairment in various cognitive areas such as language, visuospatial ability, and executive function, ultimately making independent daily living difficult.
Alzheimer's disease is the most common cause, accounting for 60-70% of all dementia cases. The older people are, the higher the prevalence is, and the number of patients is rapidly increasing along with the aging population. In ICD-10, it is classified as G30.
Causes and Pathophysiology
The core pathology of Alzheimer's disease is the abnormal accumulation of two proteins.
- Amyloid beta: It deposits outside nerve cells and forms senile plaques. It is known that accumulation begins years to decades before onset.
- Tau protein: Hyperphosphorylated, creates neurofibrillary tangles within nerve cells, breaks down the skeleton of nerve cells, and leads to cell death.
These changes start in the medial temporal lobe (hippocampus), which is responsible for memory, and gradually spread throughout the cerebral cortex. The most important risk factor is old age, and the APOE ε4 genotype increases susceptibility to disease. Vascular risk factors such as high blood pressure, diabetes, obesity, hearing loss, and social isolation are also analyzed as correctable factors that increase the risk.
symptoms
Symptoms progress in stages.
- Early: Recent memory decline is prominent. They repeat the same questions, forget appointments or where they left things, and cannot recall even when given hints.
- Middle stage: Language difficulties (difficulty finding words), visuospatial difficulties (wandering on familiar paths), and decreased executive function (difficulties with calculations and money management) become evident. It may also be accompanied by behavioral and psychological symptoms such as delusions, depression, and agitation.
- Late stage: Full assistance is required for all aspects of daily life, communication is difficult, and basic functions such as walking and swallowing are impaired.
The speed of progress varies greatly from person to person.
diagnosis
Diagnosis aims to objectively confirm cognitive decline and identify Alzheimer's pathology, and the NIA-AA (National Institute on Aging-Alzheimer's Association) criteria are widely used.
- History taking: Confirmation of onset time, progression pattern, and accompanying symptoms through guardian
- Neuropsychological test: Evaluation of cognitive areas such as memory, language, visuospatial, and executive function
- Brain imaging: MRI confirms atrophy of the hippocampus and medial temporal lobe, excludes other causes such as vascular lesions
- Biomarker: Direct confirmation of Alzheimer's pathology through amyloid PET and cerebrospinal fluid amyloid beta and tau tests
- Blood test: exclude correctable causes such as thyroid function and vitamin B12
Using biomarkers, it is possible to identify Alzheimer's pathology even in the mild cognitive impairment stage, which helps in early diagnosis and treatment decisions.
treatment
medication
Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) relieve cognitive symptoms by inhibiting the breakdown of acetylcholine and are used in mild to moderate stages. In moderate to severe stages, the NMDA receptor antagonist memantine is added. These drugs do not stop the progression of the disease but control the symptoms.
Recently, anti-amyloid antibodies that directly remove amyloid were introduced for the purpose of suppressing the progression of early Alzheimer's disease. In the CLARITY-AD study, lecanemab slowed the worsening of the Clinical Dementia Scale Summated Score (CDR-SB) by 27% compared to placebo at 18 months. However, monitoring of side effects such as amyloid-related imaging abnormalities (cerebral edema and microhemorrhage) is necessary.
Non-drug treatment
Cognitive stimulation training, regular exercise, social activities, and lifestyle management contribute to maintaining cognitive function. For behavioral and psychological symptoms, environmental adjustments and non-pharmacological approaches are given priority.
Risk Factor Management
Managing high blood pressure, diabetes, and dyslipidemia, quitting smoking, abstaining from drinking, correcting hearing, and maintaining social activities help lower the risk of developing the disease and slow its progression.