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Selective loss of dopamine d2 receptors in temporal cortex in dementia with Lewy bodies, association with cognitive decline

Selective loss of dopamine d2 receptors in temporal cortex in dementia with Lewy bodies, association with cognitive decline
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.
neuroleptic sensitivity, autoradiography, body dementia, alzheimers-disease, disease, psychosis, efficacy, parkinson's disease, parkinsons-disease patients, alzheimer's disease
0829-5283
903-911
Piggott, Margaret A.
51bc1676-4dca-459e-b8f5-00c721545e66
Ballard, Clive G.
b02237aa-9c76-4530-a8fa-1256daa73f0e
Rowan, Elise
1ac60f1d-e00c-4382-afae-4ce0c1813d04
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
McKeith, Ian G.
d10591da-19e5-4a1c-8d40-c175495bfbdb
Jaros, Evelyn
93b4fb37-33d7-4339-b1ab-96af751e6303
Perry, Robert H.
84e6f6de-d033-4eff-a2d2-2dce8c131f6e
Perry, Elaine K.
6ac4d5db-e9ed-4e4c-b7bf-29929cc42825
Piggott, Margaret A.
51bc1676-4dca-459e-b8f5-00c721545e66
Ballard, Clive G.
b02237aa-9c76-4530-a8fa-1256daa73f0e
Rowan, Elise
1ac60f1d-e00c-4382-afae-4ce0c1813d04
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
McKeith, Ian G.
d10591da-19e5-4a1c-8d40-c175495bfbdb
Jaros, Evelyn
93b4fb37-33d7-4339-b1ab-96af751e6303
Perry, Robert H.
84e6f6de-d033-4eff-a2d2-2dce8c131f6e
Perry, Elaine K.
6ac4d5db-e9ed-4e4c-b7bf-29929cc42825

Piggott, Margaret A., Ballard, Clive G., Rowan, Elise, Holmes, Clive, McKeith, Ian G., Jaros, Evelyn, Perry, Robert H. and Perry, Elaine K. (2007) Selective loss of dopamine d2 receptors in temporal cortex in dementia with Lewy bodies, association with cognitive decline. Synapse, 61 (11), 903-911. (doi:10.1002/syn.20441).

Record type: Article

Abstract

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.

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More information

Published date: 30 July 2007
Keywords: neuroleptic sensitivity, autoradiography, body dementia, alzheimers-disease, disease, psychosis, efficacy, parkinson's disease, parkinsons-disease patients, alzheimer's disease

Identifiers

Local EPrints ID: 62549
URI: http://eprints.soton.ac.uk/id/eprint/62549
ISSN: 0829-5283
PURE UUID: 45322bee-1235-44d9-8e7a-e69b46868c93
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912

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Date deposited: 12 Sep 2008
Last modified: 16 Mar 2024 03:07

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Contributors

Author: Margaret A. Piggott
Author: Clive G. Ballard
Author: Elise Rowan
Author: Clive Holmes ORCID iD
Author: Ian G. McKeith
Author: Evelyn Jaros
Author: Robert H. Perry
Author: Elaine K. Perry

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