Revisiting the cholinergic hypothesis of behavioral and psychological symptoms in dementia of the Alzheimer's type

Behavioral and psychological symptoms of dementia (BPSD) include agitation, aberrant motor behavior, anxiety, elation, irritability, depression, apathy, disinhibition, delusions, hallucinations, and sleep or appetite impairment. These symptoms have adverse consequences for patients and caregivers, such as greater impairment in activities of daily living, worsening quality of life and earlier institutionalization. While the etiology of BPSD has not been clearly delineated, studies assessing the benefits of acetylcholinesterase inhibitors on BPSD suggest that some of the neuropsychiatric symptoms of dementia such as agitation, apathy and psychosis may represent a specific central cholinergic deficiency syndrome. Biochemical and neuroimaging studies of BPSD in Alzheimer's patients support these pharmacological data. This review discusses the literature describing the association between cholinergic deficiency and manifestations of BPSD.

Research highlights
► Behavioral and psychological symptoms of dementia have adverse consequences.
► Psychosis, apathy and agitation may represent a central cholinergic deficiency.
► This syndrome is supported by the role of the cholinergic system in attention.
► Biochemical, pharmacological and neuroimaging data also support this association.