Effect of long-term treatment with tacrine (THA) in Alzheimer's disease as visualized by PET.
Among various attempts to enhance cholinergic neurotransmission in AD clinical trials with cholinesterase inhibitors have been most promising. In this study positron emission tomography (PET) was used to investigate how long-term treatment with cholinesterase inhibitors like tacrine could induce changes in the functional activity of Alzheimer brains. PET investigations measuring cerebral blood flow, glucose metabolism, nicotinic and muscarinic receptors have repeatedly been performed in patients treated with tacrine up to 2.5 years. Changes in nicotinic receptors and blood flow were observed after 3 weeks of treatment while changes in glucose metabolism were measured after 3 months of treatment. Following longer period of treatments and increase in dose of tacrine improvements were measured by PET. The most significant effects were found in patients with early forms of the dementia. The findings suggest that longer treatment may not only be symptomatic but might slow down the disease process.
Nordberg
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Department of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005260:Female; D005625:Frontal Lobe / Q000098:blood supply / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D009538:Nicotine / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects; D013619:Tacrine / Q000494:pharmacology / Q000627:therapeutic use*; D013702:Temporal Lobe / Q000098:blood supply / Q000187:drug effects; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D013619:Tacrine; D009538:Nicotine; D005947:Glucose