title: Opiate receptor avidity and cerebral blood flow in Alzheimer's disease.
abstract: Positron emission tomography was performed on 12 Alzheimer's patients and 12 age-matched normal controls following the administration of the opiate receptor antagonist 6-deoxy-6-beta-[18F]fluoronaltrexone (cyclofoxy, CF). Tracer kinetic analysis was used to determine the volume of distribution of CF, a measure of unoccupied mu and kappa receptor density, i.e. opiate receptor avidity in 34 brain regions. Regional cerebral blood flow rates (CBF) were determined on the same day with H2[15O]. Global gray CF avidity and global gray CBF were found to be lower in the Alzheimer's patients and correlated (r=0.73, P<0.03). Regional CBF differences were superimposed on global CBF changes in the Alzheimer's patients, with the subcortex relatively spared. Multivariate statistical analyses, however, failed to demonstrate regional specificity for the CF avidity changes. Furthermore, percent changes in regional CF avidity were not correlated with percent changes in regional CBF (r=0.12, P=NS). These findings demonstrate involvement of the opiate system in Alzheimer's disease. Although, neurodegeneration is the likely underlying process responsible for both the changes in CF avidity and CBF in Alzheimer's disease, the differences with respect to the patterns of these losses suggest that the intermediate mechanisms leading from neurodegeneration to loss are distinct.
authors.affiliation: Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, MD 20892-4030, USA. Bob@shiloh.nimh.nih.gov
authors.forename: R M
authors.initials: RM
authors.lastname: Cohen
authors.forename: P J
authors.initials: PJ
authors.lastname: Andreason
authors.forename: D J
authors.initials: DJ
authors.lastname: Doudet
authors.forename: R E
authors.initials: RE
authors.lastname: Carson
authors.forename: T
authors.initials: T
authors.lastname: Sunderland
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000503:physiopathology*; D001923:Brain Chemistry / Q000502:physiology; D002560:Cerebrovascular Circulation; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009271:Naltrexone; D009292:Narcotic Antagonists; D009410:Nerve Degeneration / Q000502:physiology; D011957:Receptors, Opioid / Q000378:metabolism*; D014055:Tomography, Emission-Computed
chemical_list: D005462:Fluorine Radioisotopes; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009271:Naltrexone