The International Journal of Neuropsychopharmacology



Thalamic D2 receptors in dementia with Lewy bodies, Parkinson's disease, and Parkinson's disease dementia


Margaret A. Piggott a1c1, Clive G. Ballard a2, Heather O. Dickinson a3, Ian G. McKeith a5, Robert H. Perry a4 and Elaine K. Perry a1
a1 IAH Research Laboratories, Institute for Ageing and Health, University of Newcastle-upon-Tyne, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, UK
a2 Wolfson Centre for Age-related Diseases, King's College London, Strand, London, UK
a3 Centre for Health Services Research, University of Newcastle-upon-Tyne, Newcastle upon Tyne, UK
a4 Department of Neuropathology, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, UK
a5 Institute for Ageing and Health, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, UK

Article author query
piggott ma   [PubMed][Google Scholar] 
ballard cg   [PubMed][Google Scholar] 
dickinson ho   [PubMed][Google Scholar] 
mckeith ig   [PubMed][Google Scholar] 
perry rh   [PubMed][Google Scholar] 
perry ek   [PubMed][Google Scholar] 

Abstract

Dementia with Lewy bodies (DLB) is characterized by progressive dementia with two of three core symptoms; Parkinsonism, visual hallucinations or disturbances of consciousness/fluctuating attention. Dementia in Parkinson's disease (PDD) has similar neuropsychiatric characteristics. Reduced nigrothalamic dopamine and altered thalamic D2 receptors may mediate some of the non-motor symptoms of DLB and PDD. The study aims were to ascertain whether thalamic D2 density was altered in Parkinson's disease (PD), PDD and DLB, and whether D2 density was related to core symptoms. Thalamic D2 receptor binding was measured by post-mortem autoradiography in 18 cases of DLB, 13 PDD, 6 PD and 14 normal elderly controls. Highest D2 density in control cases was in the intralaminar, midline, anterior and mediodorsal nuclei. In PD without dementia D2 binding was elevated above controls in all thalamic regions, significantly in reticular, laterodorsal, centromedian, ventral centromedian, parafascicular, paraventricular, ventroposterior, ventrolateral posterior, and ventrointermedius nuclei. Compared to controls, DLB cases with Parkinsonism (DLB+EPS) had significantly elevated D2 receptor density in laterodorsal and ventrointermedius nuclei; PDD cases had significantly raised density in the ventrointermedius, and DLB cases without Parkinsonism (DLB−EPS) did not show increased D2 density in any areas. In DLB and PDD cases with disturbances of consciousness, cases treated with neuroleptics had higher D2 binding in all thalamic regions, significantly in the mediodorsal and ventrolateral posterior nuclei. D2 receptor binding did not vary with cognitive decline (MMSE) or visual hallucinations, but was significantly higher with increased extrapyramidal symptoms.

(Received February 11 2005)
(Reviewed March 31 2005)
(Revised December 8 2005)
(Accepted December 19 2005)


Key Words: Consciousness; fluctuations; [125I]epidepride; Lewy body diseases; thalamus.

Correspondence:
c1 MRC Building, Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, NE4 6BE, UK. Tel.: (0)191 4444413 Fax: (0)191 4444402E-mail: m.a.piggott@ncl.ac.uk


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