Which neurotransmitter deficiency underlies the cognitive decline of Alzheimer disease, and is the target of drugs such as donepezil?

Correct answer: D. Acetylcholine

• A. ❌ Glutamate is relevant — memantine is an NMDA antagonist used in moderate-to-severe disease — but glutamate EXCESS (excitotoxicity) is the issue, not the primary deficiency.
• B. ❌ Dopamine loss in the substantia nigra causes PARKINSON disease.
• C. ❌ Norepinephrine is implicated in depression and anxiety states.
• D. ✅ CORRECT — Alzheimer disease features degeneration of cholinergic neurons, particularly in the nucleus basalis of Meynert, producing an ACETYLCHOLINE deficit. This is why acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) are first-line therapy.

Note: Dental relevance: cholinesterase inhibitors increase salivation and can cause bradycardia; anticholinergic drugs (including some sedatives) worsen confusion in these patients.