Imaging brain cholinergic activity with positron emission tomography: its role in the evaluation of cholinergic treatments in Alzheimer's dementia.
One of the strategies in the treatment of Alzheimer's disease is the use of drugs that enhance cholinergic brain function, since it is believed that cholinergic dysfunction is one of the factors that contributes to cognitive deterioration. Positron emission tomography is a medical imaging method that can be used to measure the concentration, kinetics, and distribution of cholinergic-enhancing drugs directly in the human brain and assess the effects of the drugs at markers of cholinergic cell viability (vesicular transporters, acetylcholinesterase), at muscarininc and nicotinic receptors, at extracellular acetylcholine, at markers of brain function (glucose metabolism and blood flow), and on amyloid plaque burden in vivo in the brains of patients with Alzheimer's disease. In addition, these measures can be applied to assess the drugs' pharmacokinetic and pharmacodynamic properties in the human brain. Since the studies are done in living human subjects, positron emission tomography can evaluate the relationship between the drugs' biological, behavioral, and cognitive effects; monitor changes in brain function in response to chronic treatment; and determine if pharmacologic interventions are neuroprotective. Moreover, because positron emission tomography has the potential to identify Alzheimer's disease during early disease, it can be used to establish whether early interventions can prevent or delay further development.
Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
N D
ND
Volkow
Y S
YS
Ding
J S
JS
Fowler
S J
SJ
Gatley
D000109:Acetylcholine / Q000502:physiology; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D018678:Cholinergic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
D018678:Cholinergic Agents; D011978:Receptors, Nicotinic; D000109:Acetylcholine