Jawaharlal Nehru Technological University Hyderabad Pharm.D IV Year PHARMACOTHERAPEUTICS - III Previous Question Paper (October - 2019 - R08)

Pathogenesis: Alzheimer’s disease is primarily driven by the accumulation of extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. This leads to synaptic dysfunction, loss of cholinergic neurons, and widespread neurodegeneration, particularly in the hippocampus and cerebral cortex. Chronic neuroinflammation and oxidative stress further exacerbate neuronal death.

Symptoms: The clinical presentation follows a progressive decline in cognitive and functional abilities:

• Early stage: Short-term memory loss, difficulty learning new information, and mild word-finding problems.
• Middle stage: Disorientation to time and place, impaired executive function, personality changes, and behavioral disturbances (agitation, wandering).
• Late stage: Severe cognitive impairment, loss of verbal communication, physical decline (incontinence, dysphagia), and total dependence for activities of daily living.

Management: Treatment focuses on symptom management and improving quality of life, as there is currently no cure.

1. Pharmacotherapy: Acetylcholinesterase inhibitors (e.g., Donepezil, Rivastigmine, Galantamine) are used for mild to moderate cases to increase synaptic acetylcholine levels. NMDA receptor antagonists (e.g., Memantine) are used in moderate to severe stages to reduce glutamate-induced excitotoxicity.
2. Non-pharmacological management: Cognitive stimulation therapy, structured routines, and environmental modifications to ensure safety and reduce confusion.
3. Supportive care: Management of comorbid conditions, nutritional support, and caregiver education to address the psychological and physical burden of caregiving.