Antidementia drugs

Abstract

Alzheimer’s disease (AD) is the most commonly occurring dementia and consists of both cognitive impairment and behavioral disturbances. Two types of medication classes are approved by the regulatory agencies for AD treatment. The cholinesterase inhibitors (ChEIs) are used for patients with mild, moderate, and severe AD. Memantine (MEM) is indicated for moderate to severe AD patients. ChEIs and MEM are often combined together for treatment. The pharmacokinetics (PK) of the ChEIs is well known. Donepezil and galantamine display linear PK, whereas rivastigmine has nonlinear PK. Donepezil and galantamine are metabolized by the CYP2D6 and CYP3A4 enzymes. Rivastigmine is metabolized by the hepatic esterases. MEM is not significantly metabolized by the hepatic enzymes and is primarily excreted by the kidneys. Dosage adjustments are recommended for patients with severe hepatic and renal impairment. The clinical pharmacodynamic (PD) properties for the ChEIs and MEM can be assessed by various biomarkers that include cholinesterase enzyme inhibition, clinical rating scales for cognitive impairment and behavioral symptoms, and PET scan evaluations. Pharmacogenetic status is in its early utilization phase of clinical utility in AD patients. PET scans may provide useful information on patient response to ChEIs and MEM. The gastrointestinal adverse side effects limit ChEIs, but these effects are transient and associated with dose titration. Population PK analysis can integrate the PK, PD, and pharmacogenetic data to optimize treatment in patients with AD.