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๐Ÿ“š Alzheimer’s Disease – Detailed Version

๐Ÿ” 1. What is Alzheimer’s Disease (AD)?

  • Definition:
    Alzheimer’s disease is a chronic, progressive neurodegenerative disorder that primarily affects older adults, leading to memory loss, cognitive decline, and behavioral disturbances.

  • It is the most common cause of dementia, accounting for 60–80% of cases.

๐Ÿง  2. Pathophysiology (How does it happen?)

AD is characterized by degeneration of neurons in the cerebral cortex and hippocampus, leading to brain atrophy. The two key pathological hallmarks are:

๐Ÿ”ธ A. Amyloid Plaques

  • Composed of beta-amyloid (Aฮฒ) peptides, especially Aฮฒ42.

  • Accumulate extracellularly, disrupting neuronal communication and triggering inflammation.

  • Believed to be formed due to an imbalance between production and clearance of Aฮฒ.

๐Ÿ”ธ B. Neurofibrillary Tangles (NFTs)

  • Composed of hyperphosphorylated tau protein, which normally stabilizes microtubules.

  • In AD, tau becomes abnormal and forms intracellular tangles, disrupting transport within neurons and causing cell death.

๐Ÿ”ธ C. Other Key Features

  • Neuronal loss: especially in the hippocampus (memory center) and cerebral cortex (cognition, language).

  • Cholinergic deficit: loss of acetylcholine in the brain, contributing to memory impairment.

  • Brain atrophy: seen as widened sulci and enlarged ventricles on imaging.

๐Ÿงฌ 3. Risk Factors

๐Ÿ”ธ Age (biggest risk factor) – common after 65 years.
๐Ÿ”ธ Genetic factors:

  • APOE ฮต4 allele increases risk.

  • Familial early-onset Alzheimer’s (rare) linked to mutations in APP, PSEN1, PSEN2 genes.
    ๐Ÿ”ธ Other risk factors: female gender, vascular disease, low education level, head trauma.

๐Ÿ“– 4. Clinical Features (Symptoms & Stages)

๐Ÿ”น A. Early Stage (Mild)

  • Short-term memory loss (often first symptom).

  • Word-finding difficulty (anomia).

  • Mild disorientation, losing objects.

๐Ÿ”น B. Middle Stage (Moderate)

  • Worsening memory and cognition.

  • Difficulty with daily tasks (e.g., handling finances).

  • Disorientation to time/place.

  • Behavioral changes: agitation, wandering, paranoia.

  • Language deficits (aphasia) and motor planning issues (apraxia).

๐Ÿ”น C. Late Stage (Severe)

  • Severe memory loss, unable to recognize family.

  • Loss of speech and mobility.

  • Incontinence.

  • Complete dependence for care.

  • Prone to infections (e.g., pneumonia).

๐Ÿงช 5. Diagnosis

๐Ÿ”ธ Clinical Assessment

  • History and mental status exam.

  • Cognitive testing:

    • MMSE (Mini-Mental State Exam) – score out of 30; <24 suggests cognitive impairment.

    • MoCA (Montreal Cognitive Assessment) – more sensitive for mild impairment.

๐Ÿ”ธ Laboratory Tests (to rule out other causes)

  • TSH, B12, folate, electrolytes, liver/kidney function.

๐Ÿ”ธ Neuroimaging

  • MRI or CT:

    • Shows cortical atrophy, especially in hippocampus and temporal-parietal lobes.

    • Exclude other causes (stroke, tumor).

๐Ÿ”ธ Definitive Diagnosis

  • Post-mortem brain examination revealing amyloid plaques and NFTs.

๐Ÿ’Š 6. Management

๐Ÿ”น A. Non-Pharmacological (Mainstay of Care)

✅ Cognitive stimulation therapy (puzzles, reading, conversation).
✅ Behavioral management – reassurance, routines, environmental cues.
✅ Caregiver support – education, counseling.
✅ Safety measures – prevent wandering, install alarms, label doors.

๐Ÿ”น B. Pharmacological Treatment

  • Cholinesterase inhibitors (for mild to moderate AD):

    • Donepezil, Rivastigmine, Galantamine – improve cholinergic transmission.

  • NMDA receptor antagonist (for moderate to severe AD):

    • Memantine – reduces excitotoxicity from glutamate.

  • Symptomatic treatments:

    • Antidepressants, antipsychotics (only if severe agitation/psychosis, and with caution).

๐Ÿ”น C. Experimental/Research Approaches

  • Monoclonal antibodies targeting amyloid (e.g., Aducanumab – limited approval).

  • Ongoing trials targeting tau and inflammation.

๐Ÿšจ 7. Complications

  • Falls and fractures.

  • Infections (aspiration pneumonia, UTIs).

  • Malnutrition and dehydration.

  • Wandering and injury.

  • Caregiver burnout.

๐ŸŽ“ 8. Summary Table

Feature Description
Definition Progressive neurodegeneration causing dementia
Pathology Amyloid plaques + neurofibrillary tangles
Key neurotransmitter Acetylcholine deficit
Early symptoms Memory loss, word-finding difficulty
Diagnosis Clinical + cognitive tests + imaging
Treatment Cholinesterase inhibitors, memantine
Prognosis Gradual decline over 8–10 years


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