Selective loss of dopamine D2 receptors in temporal cortex in dementia with Lewy bodies, association with cognitive decline.
Dementia with Lewy bodies (DLB) is a progressive dementia frequently accompanied by psychotic symptoms. Similar symptoms can occur in Alzheimer's disease (AD) to a lesser extent. The use of neuroleptic medication to treat psychosis in both diseases is of modest efficacy and can induce severe adverse reactions in DLB. Dopamine D2 receptors in the cerebral cortex are the putative target for the antipsychotic action of these drugs, but the status of these receptors in DLB is unknown. Autoradiography was used to examine the density D2 receptors in postmortem temporal cortex tissue from prospectively assessed patients with neuropathologically confirmed DLB and AD. D2 receptors were substantially (over 40%) and significantly (P < 0.001) reduced in temporal cortex in DLB, and in DLB with concomitant Alzheimer pathology, but was not significantly changed in AD. This reduction correlated with greater cognitive decline (P < 0.01), but was not significantly related to visual or auditory hallucinations or delusions. D2 receptor density was inversely correlated with cortical Lewy body pathology in the neocortex (P < 0.001). The specific loss of D2 receptors associated with Lewy body pathology, in conjunction with our previous finding of low D2 receptors in striatum in DLB, provides a possible explanation for neuroleptic intolerance. That the reduction of D2 receptors correlated with cognitive decline suggests that neuroleptics, as dopamine D2 receptor antagonists, may have a deleterious effect on cognition in DLB.
Piggott
Margaret A
MA
Institute for Ageing and Health, Wolfson Research Centre, Newcastle General Hospital, Newcastle-upon-Tyne NE4 6BE, United Kingdom. m.a.piggott@ncl.ac.uk
Ballard
Clive G
CG
Rowan
Elise
E
Holmes
Clive
C
McKeith
Ian G
IG
Jaros
Evelyn
E
Perry
Robert H
RH
Perry
Elaine K
EK
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001549:Benzamides / Q000493:pharmacokinetics; D001923:Brain Chemistry / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology*; D005260:Female; D006801:Humans; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D020961:Lewy Body Disease / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011180:Postmortem Changes; D011759:Pyrrolidines / Q000493:pharmacokinetics; D011859:Radiography / Q000379:methods; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013702:Temporal Lobe / Q000187:drug effects / Q000378:metabolism*
D001549:Benzamides; D007456:Iodine Isotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C063525:epidepride