Cholinergic deficit in Alzheimer disease — MRCPsych Paper A MCQ

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EasyNeurophysiology and neurochemistryCholinergic deficit in Alzheimer diseaseMRCPsych Paper A

A 76-year-old man with Alzheimer disease has progressive impairment of attention and memory. Post-mortem examination shows degeneration of large basal forebrain neurons with widespread projections to the cerebral cortex. Which neurotransmitter–source pairing is most characteristically affected?

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Correct answer: A — Acetylcholine — nucleus basalis of Meynert

The correct answer is A. The nucleus basalis of Meynert is a major component of the basal forebrain cholinergic system and provides widespread acetylcholine projections to the cerebral cortex. Degeneration of this pathway in Alzheimer disease contributes to impaired attention, learning and memory and provides the rationale for symptomatic treatment with acetylcholinesterase inhibitors. Ventral tegmental dopamine is principally associated with reward and motivation. Raphe serotonin contributes to mood, sleep and other functions but is not the characteristic pathway described. Purkinje cells provide GABAergic output from the cerebellar cortex and are primarily involved in motor coordination. Lateral hypothalamic orexin neurons regulate arousal and sleep–wake stability.

Reference: Mesulam MM. Cholinergic circuitry of the human nucleus basalis and its fate in Alzheimer's disease. Journal of Comparative Neurology. 2013;521:4124–4144. https://pubmed.ncbi.nlm.nih.gov/23852922/