 |
|
Alterations of Striatal Dopamine Receptor Binding in Alzheimer Disease Are Associated With Lewy Body Pathology and Antemortem Psychosis
Robert A. Sweet, MD;
Ronald L. Hamilton, MD;
Matthew T. Healy, MEd;
Stephen R. Wisniewski, PhD;
Ruth Henteleff, AB;
Bruce G. Pollock, MD, PhD;
David A. Lewis, MD;
Steven T. DeKosky, MD
Arch Neurol. 2001;58:466-472.
Background Lewy bodies (LB) are present in at least 20% to 30% of persons with
Alzheimer disease (AD) and contribute to the risk of psychosis and to excess
cognitive burden.
Objective To determine whether altered striatal dopamine receptor binding is associated
with LB and psychosis in AD.
Design Postmortem case control.
Setting Alzheimer's Disease Research Center at the University of Pittsburgh
(Pa).
Participants Consecutive cases from the Alzheimer's Disease Research Center brain
bank, neuroleptic free for at least 1 month prior to death, with neuropathologic
diagnoses of AD with LB (AD + LB, n = 14), AD without LB (AD, n = 13), or
normal brains (n = 8).
Main Outcome Measures Dopamine D1, D2, and D3 receptor densities,
and affinities as determined by selective saturation binding studies in striatal
tissue.
Results Subjects with AD + LB, compared with those with AD, demonstrated increased
D1 receptor density and decreased D2 and D3
receptor density. D3 receptor density was selectively increased,
however, in AD subjects with a history of psychosis, independent of the presence
or absence of LB. The effect of neuroleptic treatment on D3 binding
was further examined in an additional group of subjects who had received neuroleptics
near the time of death. Neuroleptic treatment reduced D3 affinity
with no effect on D3 density.
Conclusions Alzheimer disease with LB is associated with selective alterations in
dopamine receptor density, which may contribute to the distinct clinical profile
of this group. The D3 receptor may be an important target of neuroleptic
treatment of psychosis in AD.
From the Division of Geriatrics and Neuropsychiatry (Drs Sweet, Pollock,
and DeKosky, Mr Healy, and Ms Henteleff), Department of Psychiatry (Dr Lewis),
and the Division of Neuropathology, Department of Pathology (Dr Hamilton),
School of Medicine, and the Department of Epidemiology, Graduate School of
Public Health (Dr Wisniewski), University of Pittsburgh, Pittsburgh, Pa.
Corresponding author and reprints: Robert A. Sweet, MD, Western Psychiatric
Institute and Clinic, 3811 O'Hara St, Pittsburgh, PA 15213 (e-mail: Sweetra{at}msx.upmc.edu).
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED ARTICLE
Archives of Neurology Reader's Choice: Continuing Medical Education
Arch Neurol. 2001;58(3):523-525.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Increased striatal dopamine (D2/D3) receptor availability and delusions in Alzheimer disease
Reeves et al.
Neurology 2009;72:528-534.
ABSTRACT
| FULL TEXT
Delusions and Hallucinations in Alzheimer's Disease: Review of the Brain Decade
Bassiony and Lyketsos
Psychosomatics 2003;44:388-401.
ABSTRACT
| FULL TEXT
Psychotic genes or forgetful ones?
Lovestone and Hardy
Neurology 2002;59:11-12.
FULL TEXT
Apolipoprotein E and Alpha-1-Antichymotrypsin Genotypes Do Not Predict Time to Psychosis in Alzheimer's Disease
Sweet et al.
J Geriatr Psychiatry Neurol 2002;15:24-30.
ABSTRACT
|
