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Demonstration of a reduction in muscarinic receptor binding in early Alzheimer's disease using iodine-123 dexetimide single-photon emission tomography

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Abstract

Decreased muscarinic receptor binding has been suggested in single-photon emission tomography (SPET) studies of Alzheimer's disease. However, it remains unclear whether these changes are present in mildly demented patients, and the role of cortical atrophy in receptor binding assessment has not been investigated. We studied muscarinic receptor binding normalized to neostriatum with SPET using [123I]4-iododexetimide in five mildly affected patients with probable Alzheimer's disease and in five age-matched control subjects. Region of interest (ROI) analysis was performed in a consensus procedure blind to clinical diagnosis using matched magnetic resonance (MRI) images. Cortical atrophy was assessed by calculating percentages of cerebrospinal fluid in each ROI. An observer study with three observers was conducted to validate this method. Alzheimer patients showed statistically significantly less [123I]4-iododexetimide binding in left temporal and right temporo-parietal cortex compared with controls, independent of age, sex and cortical atrophy. Mean intea-observer variability was 3.6% and inter-observer results showed consistent differences in [123I]4-iododexetimide binding between observers. However, differences between patients and controls were comparable among observers and statistically significant in the same regions as in the consensus procedure. Using an MRI-SPET matching technique, we conclude that [123I]4-iododexetimide binding is reduced in patients with mild probable. Alzheimer's disease in areas of temporal and temporoparietal cortex.

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Authors and Affiliations

  1. Department of Neurology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Jules J. Claus

  2. Department of Nuclear Medicine, Academic Medical Center, The Netherlands

    Eric A. Dubois, Jan Booij, Jan Habraken & Eric A. van Royen

  3. The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

    Jan C. de Munck & Marcel van Herk

  4. Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands

    Bernard Verbeeten Jr.

Authors
  1. Jules J. Claus
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  2. Eric A. Dubois
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  3. Jan Booij
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  4. Jan Habraken
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  5. Jan C. de Munck
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  6. Marcel van Herk
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  7. Bernard Verbeeten Jr.
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  8. Eric A. van Royen
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Claus, J.J., Dubois, E.A., Booij, J. et al. Demonstration of a reduction in muscarinic receptor binding in early Alzheimer's disease using iodine-123 dexetimide single-photon emission tomography. Eur J Nucl Med 24, 602–608 (1997). https://doi.org/10.1007/BF00841396

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  • DOI: https://doi.org/10.1007/BF00841396

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