Dementia and Its Treatment

• Causes, pathology, and clinical features of dementia
• Alzheimer dementia, beta amyloid plaques, and neurofibrillary tangles
• Amyloid cascade hypothesis
• Apo-E and the risk of Alzheimer’s disease
• Are there predementia states?
• Amnestic mild cognitive impairment (MCI)
• Depression: harbinger of dementia?
• Symptomatic treatments for dementia
• Acetylcholine and the pharmacological basis of cholinesterase treatments for dementia
• Cholinergic deficiency hypothesis of amnesia in Alzheimer’s disease and other dementias
• Cholinesterase inhibitors
• Memantine
• Other proposed treatments
• Future treatments
• Marketed products with potential therapeutic actions in dementia
• Disease-modifying agents in development that act on amyloid processing
• Other potential disease-modifying treatment approaches
• Symptomatic treatments in development for Alzheimer’s disease and other cognitive disorders and dementias
• The dementia pharmacy
• Summary

Dementia and Its Treatment

Dementia is an area of psychopharmacology where symptomatic treatments are already available. However, the most exciting aspect to this field is the possibility of disease-modifying treatments on the horizon, particularly for Alzheimer’s disease. Imagine the impact of new treatments that could halt the progression of this disorder or even partially reverse it! The goal of this chapter is to provide the biological background that will enable the reader to understand not only how currently symptomatic treatments for Alzheimer’s disease work but also the rationale for current research efforts to discover truly disease-modifying treatments for this debilitating illness.

This chapter therefore provides only a very brief overview of the various causes of dementias and their pathologies. Full clinical descriptions and formal criteria for the diagnosis of the numerous known dementias should be obtained by consulting standard

reference sources. The discussion here emphasizes the links between various pathological mechanisms, brain circuits, and neurotransmitters with the various symptoms of dementia, especially those of Alzheimer’s disease. The goal of this chapter is to acquaint the reader with ideas about the clinical and biological aspects of dementia and its currently approved treatments as well as the many exciting treatments that are on the horizon. The emphasis here is on the biological basis of symptoms of dementia and of their relief by psychopharmacological agents as well as the mechanism of action of drugs that treat these symptoms. For details of doses, side effects, drug interactions, and other issues relevant to the prescribing of these drugs in clinical practice, the reader should consult standard drug handbooks (such as Essential Psychopharmacology: Prescriber’s Guide).