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This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jnumed.109.064030v1 50/9/1455    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Mitsis, E. M. Articles by van Dyck, C. H. PubMed PubMed Citation Articles by Mitsis, E. M. Articles by van Dyck, C. H.

¹²³I-5-IA-85380 SPECT Imaging of Nicotinic Receptors in Alzheimer Disease and Mild Cognitive Impairment

Effie M. Mitsis^1–3, Kristina M. Reech^1,2, Frederic Bois², Gilles D. Tamagnan^2–4, Martha G. MacAvoy^1,2, John P. Seibyl^2–5, Julie K. Staley^,2,3 and Christopher H. van Dyck^1,2,6

¹ Alzheimer's Disease Research Unit, Yale University School of Medicine, New Haven, Connecticut; ² Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; ³ Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; ⁴ Institute for Neurodegenerative Disorders, New Haven, Connecticut; ⁵ Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut; and ⁶ Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut

Correspondence: For correspondence or reprints contact: Christopher H. van Dyck, Alzheimer's Disease Research Unit, Yale University School of Medicine, One Church St., Suite 600, New Haven, CT 06510. E-mail: christopher.vandyck{at}yale.edu

Postmortem binding studies have established that the concentration of ₄β₂-nicotinic acetylcholine receptors (₄β₂-nAChR) is reduced in advanced Alzheimer disease (AD). However, the status of this receptor in mild or prodromal AD has remained the subject of controversy. Methods: We compared ₄β₂-nAChR availability in 8 brain regions of living human subjects who had AD and mild cognitive impairment (MCI) with that in age-matched healthy control subjects by using the ligand ¹²³I-5-IA-85380 (¹²³I-5-IA) and SPECT. All subjects (n = 32) were nonsmokers; they were administered ¹²³I-5-IA as a bolus plus a constant infusion and imaged 6–8 h later under equilibrium conditions. The effect of diagnosis on regional ₄β₂-nAChR availability (regional brain activity/total parent concentration in plasma, proportional to the binding potential) was analyzed using multivariate analysis of covariance, controlling for the effects of age and sex. Results: Despite a significant overall effect of diagnostic group on mean ₄β₂-nAChR availability, univariate analyses revealed no group differences for any brain region analyzed. An exploratory analysis of the relationship between regional ₄β₂-nAChR availability and neuropsychologic variables yielded several plausible correlations. However, after Bonferroni adjustment, only the correlation between the anterior cingulate and the Trail Making Test, Part B, in the healthy control subjects remained significant. Conclusion: These results are consistent with several postmortem and in vivo studies suggesting the preservation of nAChRs during the prodromal and early stages of AD. They support the interpretation that nAChR and other cholinergic reductions in AD are late-stage phenomena.

Key Words: nicotinic receptors • Alzheimer disease • mild cognitive impairment • ¹²³I-5-IA-85380 • SPECT

Deceased.

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.

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