Chapter 18: Antidementia Drugs & Cognitive Disorders

The primary focus is on the pathophysiology of cognitive decline, characterized by neuronal death and a critical deficiency in the neurotransmitter acetylcholine within memory-forming centers like the hippocampus and amygdala. The text explains the role of enzymes such as acetylcholinesterase and butyrylcholinesterase in metabolizing acetylcholine, providing the scientific basis for using cholinesterase inhibitors to bolster neurotransmission. Detailed profiles are provided for key drugs: the historical and hepatotoxic tacrine; donepezil, a selective and reversible inhibitor with a long half-life; rivastigmine, which forms a covalent bond for irreversible inhibition; and galantamine, noted for its dual action of inhibiting enzymes and modulating presynaptic nicotinic receptors to potentially offer neuroprotection. The narrative shifts to addressing neuronal excitotoxicity caused by overactive glutamate signaling, introducing memantine as an NMDA receptor antagonist that regulates calcium influx to prevent cell death without blocking essential learning signals. Additionally, the chapter explores emerging theories and experimental treatments, including secretase inhibitors and dihydropyridine calcium channel blockers, as well as the controversial and investigational use of nonsteroidal anti-inflammatory drugs, statins, and vitamin supplements in the prevention of cognitive deterioration.