Alzheimer's disease

Disease Description (Causes and Pathophysiology, Main Symptoms)

• Summary of definition
  Alzheimer's disease is a degenerative brain disease in which amyloid-beta plaques and neurofibrillary tangles of tau protein accumulate in the brain, progressively damaging and destroying nerve cells. It is the most common cause of dementia.

• Pathophysiology (briefly)

  • Accumulation of amyloid-beta and plaque formation due to abnormal processing of amyloid precursor protein (APP)
  • Neurofibrillary tangles (tau pathology) caused by hyperphosphorylation of tau protein
  • Progression of synaptic loss, neuronal death, and brain atrophy (particularly in the hippocampus and temporal lobe)
  • Decline in the function of the cholinergic neurotransmitter system (associated with memory and learning impairment)
  • Genetic factors (such as ApoE ε4) and cardiovascular risk factors (hypertension, diabetes, hyperlipidemia, and obesity) contribute to the risk of developing the disease

• Main symptoms (common clinical manifestations)

  • Early stage: Impaired registration of new information and short-term memory (misplacing objects, repeating the same questions)
  • As the disease progresses: Loss of long-term memory, difficulty finding names and words (aphasia), difficulty performing daily activities (apraxia), visuospatial impairment (loss of sense of direction), agnosia, and reduced judgment
  • Behavioral and emotional symptoms: Depression, anxiety, agitation, aggression, delusions (such as theft delusions), mood swings, and nighttime confusion (sundowning)
  • Risk of complications: Falls, reduced nutritional intake, infections (such as pneumonia), and possible development of delirium

Treatment Methods and Precautions

• Goals
  Slow disease progression and relieve cognitive and behavioral symptoms, maintain daily functioning, and improve the quality of life of the patient and family

• Medication treatment (standard and major options)

  • Cholinesterase inhibitors: donepezil, rivastigmine, and galantamine
    • Indications: Used in mild to moderate Alzheimer's disease to improve cognitive function and delay worsening
    • Side effects: Gastrointestinal symptoms, muscle cramps, bradycardia, and others
  • NMDA receptor antagonist: memantine
    • Used in moderate to severe disease; may be used in combination with donepezil and other medications
    • Side effects: Dizziness, headache, constipation, and others
  • Anti-amyloid monoclonal antibodies (considered selectively when criteria are met)
    • Medications that target the removal of amyloid plaques (for example, some approved medications require strict patient selection and imaging/blood monitoring)
    • Effects are limited to slowing the rate of cognitive decline, and monitoring for hemorrhagic side effects (ARIA: cerebral edema, microhemorrhages, and others) is necessary
  • Medications for symptom management
    • Depression: Antidepressants (SSRIs, etc.)
    • Anxiety, agitation, and sleep disorders: Nonpharmacological approaches first; medication may be considered in severe cases
    • Psychosis (severe delusions and aggression): Use atypical antipsychotics at the minimum dose for the shortest possible period (be aware of the possibility of side effects and increased risk of death)

• Nonpharmacological treatment (strongly recommended)

  • Cognitive rehabilitation and cognitive stimulation programs, occupational therapy, and physical and exercise therapy
  • Environmental modifications (a safe living environment, maintaining daily routines, and removing risk factors)
  • Education, counseling, and support for family members and caregivers (stress management and caregiving education)

• Monitoring and precautions

  • In cases of sudden cognitive decline, check for reversible causes such as infection, metabolic abnormalities, medication side effects, and delirium
  • Monitoring for ARIA based on imaging (such as MRI) is necessary during anti-amyloid treatment
  • Pay attention to drug interactions, cardiovascular side effects (bradycardia), and increased fall risk in older adults
  • When the ability to drive or make financial or legal decisions declines, safety measures and advance planning are recommended (in consultation with the medical team)

Checklist Before an Outpatient Visit (Preparation and Tests)

• Items and information to bring

  • A list of current medications and health supplements (including doses and times of administration)
  • Past medical history (cardiovascular and other medical conditions, surgeries, and previous neurological test results)
  • Results of recent blood tests, electrocardiogram, chest X-ray, and brain imaging (MRI/CT/PET), if available
  • The timing and course of symptom onset (when and how symptoms began), and records of changes in daily life (for example, ability to perform daily activities, problems with thinking or managing money)
  • Records of recent events such as accidents, falls, infections, and changes in sleep
  • If possible, it is recommended that a caregiver or family member who is usually with the patient accompany them (to help observe changes in function and behavior)

• Common tests performed during medical visits (helpful for diagnosis and follow-up)

  • Blood tests: Thyroid function, vitamin B12, electrolytes, hemoglobin A1c, and others to rule out reversible causes
  • Neuropsychological testing (assessment of memory, language, and executive function)
  • Brain imaging: MRI (to identify structural atrophy and vascular lesions), CT (if necessary)
  • Biomarkers: Amyloid PET or CSF testing (to check for amyloid and tau and to consider treatment eligibility)
  • Additional tests: EEG, electrocardiogram, and others if necessary

Examples of General Questions to Ask the Doctor

• What are the expected effects and possible side effects of this medication (the medication presented)?
• What is the purpose, benefit, and burden of the tests recommended for my current condition (for example, amyloid PET or CSF testing)?
• What prognosis can be expected with treatment (the pattern of changes in cognitive function)?
• Among lifestyle factors (exercise, diet, and sleep), what should I prioritize improving now?
• When should safety measures related to driving, managing money, and making legal decisions be implemented?

Examples of Disease-Specific Questions

• Should I (or the patient) undergo amyloid biomarker testing (blood/CSF/PET)? How would the test results affect treatment choices (for example, anti-amyloid treatment) or prognosis?
• Please explain whether apolipoprotein E (ApoE) genetic testing is recommended and what the results would mean for treatment decisions, particularly anti-amyloid treatment.