A 68-year-old man with a 3-year history of progressive memory loss and cognitive decline presents to the psychiatric outpatient clinic. His wife reports gradual onset of disorientation, difficulty with complex tasks, and personality changes over months. Neuroimaging shows cerebral atrophy. He is alert, oriented to person and place but not time, and has intact attention. What is the drug of choice for cognitive symptom management in this patient?

## Diagnosis: Dementia (Alzheimer Type) The clinical presentation—insidious onset over years, progressive cognitive decline, memory loss, disorientation, personality changes, and cerebral atrophy on imaging—is classic for **Alzheimer dementia**. Attention is preserved (unlike delirium), and the course is chronic. ## Drug of Choice: Acetylcholinesterase Inhibitors **Key Point:** Donepezil is the first-line pharmacological agent for mild-to-moderate Alzheimer dementia. It is an acetylcholinesterase inhibitor that increases synaptic acetylcholine by slowing degradation. **High-Yield:** Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) are indicated in Alzheimer dementia to slow cognitive decline. Donepezil is preferred due to once-daily dosing and better tolerability. **Clinical Pearl:** These agents do not reverse dementia but slow progression by 6–12 months. They are most effective in mild-to-moderate stages; efficacy diminishes in severe dementia. ## Mechanism & Rationale Alzheimer dementia involves cholinergic neuronal loss in the basal forebrain. Acetylcholinesterase inhibitors preserve remaining acetylcholine, improving neurotransmission and cognitive function. ### Donepezil Dosing - Initial: 5 mg once daily at bedtime - Maintenance: 10 mg once daily (after 4–6 weeks) - Onset: 2–4 weeks; peak effect at 8–12 weeks ## Why Not the Other Agents? | Agent | Role in Dementia | Limitation | |-------|------------------|------------| | Haloperidol | Behavioral disturbance only | Not cognitive; high EPS risk in elderly | | Lorazepam | Acute agitation/anxiety | Not for cognitive decline; risk of dependence | | Risperidone | Behavioral/psychotic symptoms | Not first-line for cognition; increased mortality in elderly dementia | **Mnemonic:** **ACE** = **A**cetylcholinesterase inhibitors for **C**ognitive decline in **E**lderly (Alzheimer).