JNTU Pharm. D I Year PHARMACOTHERAPEUTICS - III Previous Question Paper (October - 2019 - R08)

Pathogenesis: Alzheimer’s disease is characterized by the progressive accumulation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein. These deposits lead to synaptic dysfunction, neuronal death, and cholinergic deficit, particularly in the hippocampus and cerebral cortex. Chronic neuroinflammation and oxidative stress further exacerbate neuronal loss, leading to global brain atrophy.

Symptoms: The clinical presentation follows a progressive decline in cognitive and functional abilities. Early stages involve short-term memory loss, difficulty in learning new information, and mild disorientation. As the disease advances, patients exhibit language impairment (aphasia), loss of executive function, personality changes, and behavioral disturbances such as agitation, aggression, and wandering. In the final stages, there is a total loss of motor function, speech, and basic self-care capabilities.

Management: Treatment focuses on symptomatic relief and slowing cognitive decline, as there is currently no cure.

• Pharmacological Therapy: Cholinesterase inhibitors (e.g., Donepezil, Rivastigmine, Galantamine) are used for mild-to-moderate disease to increase synaptic acetylcholine levels. For moderate-to-severe cases, the NMDA receptor antagonist Memantine is used to regulate glutamate activity and prevent excitotoxicity.
• Non-Pharmacological Management: Cognitive stimulation therapy, physical exercise, and structured routines help maintain functional independence. Caregiver support and environmental modifications are essential to manage behavioral symptoms and ensure patient safety.
• Comorbidity Management: Addressing cardiovascular risk factors, depression, and sleep disturbances is critical to improving the patient's quality of life.