## Clinical Diagnosis This patient presents with **Alzheimer's dementia** (progressive, insidious onset; cortical atrophy; stable orientation without fluctuation). ## Drug of Choice for Cognitive Symptoms **Key Point:** Donepezil is a cholinesterase inhibitor and the first-line pharmacological agent for cognitive decline in Alzheimer's dementia. ### Mechanism of Action Donepezil inhibits acetylcholinesterase, increasing synaptic acetylcholine levels in the cortex and hippocampus, thereby slowing cognitive decline. ### Efficacy & Indications | Feature | Donepezil | |---------|----------| | **Indication** | Mild to moderate Alzheimer's dementia | | **Onset of benefit** | 4–6 weeks | | **Effect size** | Slows decline by ~30% over 12 months | | **Dosing** | 5–10 mg once daily (evening) | | **Adverse effects** | Bradycardia, syncope, GI upset, muscle cramps | **High-Yield:** Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are the only disease-modifying agents with evidence in Alzheimer's dementia. They do NOT reverse cognitive loss but slow progression. ### Other Agents in Dementia Management - **Memantine** (NMDA antagonist): added in moderate-to-severe disease; synergistic with cholinesterase inhibitors. - **Antipsychotics** (haloperidol, risperidone): reserved for behavioral/psychotic symptoms, NOT primary cognitive decline; associated with stroke risk in elderly. - **Benzodiazepines** (lorazepam): cause cognitive impairment; contraindicated in dementia. **Clinical Pearl:** Donepezil is started at 5 mg daily and titrated to 10 mg after 4–6 weeks. Monitor heart rate and blood pressure due to cholinergic effects. **Warning:** Do NOT confuse donepezil (for dementia) with antipsychotics (for delirium/behavioral symptoms). Antipsychotics worsen cognition in dementia and increase mortality in elderly patients.
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