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A Spatial Covariance 1235IA-85380 SPECT Study of α4β2 Nicotinic Receptors in Dementia with Lewy Bodies

Published online by Cambridge University Press:  20 June 2025

Judith Harrison ,
Sean Colloby ,
John O’Brien  and
John Paul Taylor
Judith Harrison
Affiliation:
1Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, United Kingdom 2Northumbria NHS Healthcare Foundation Trust, Newcastle, United Kingdom
Sean Colloby
Affiliation:
1Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, United Kingdom
John O’Brien
Affiliation:
3Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
John Paul Taylor
Affiliation:
1Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, United Kingdom 4Central Newcastle Tyne and Wear (CNTW) MHS Foundation Trust, Newcastle, United Kingdom
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Abstract

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Aims: Cholinergic dysfunction is key in dementia with Lewy bodies (DLB), and likely to influence the cognitive and psychiatric symptoms of this condition. However, patterns of spatial covariance in DLB in terms of nicotinic acetylcholine receptors (nAChRs) is unknown. In this study we used 123I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (1235IA-85380) SPECT (α4β2 nAChR assessment) to investigate the covariance patterns in DLB and their associations with cognition.

Methods: Fifteen DLB and 16 healthy controls underwent 1235IA-85380 and rCBF (99mTc-exametazime) SPECT scanning. We applied voxel principal components (PC) analysis, generating a series of PC images representing common intercorrelated voxels across subjects. Linear regression generated specific α4β2 nicotinic and rCBF covariance patterns that contrasted DLB from controls.

Results: A α4β2 pattern that distinguished patients from controls (F1,29 = 165.1, p<0.001), showed relative decreased uptake in bilateral temporal pole, inferior frontal, amygdala, olfactory cortex, insula, anterior/mid cingulate and putamen, as well as relative preserved/increased uptake in sensorimotor, fusiform and occipital lobe, implicating regions in a nicotinic receptor expression sense, within limbic, salience, default mode, olfactory, sensorimotor and visual networks. We then successfully derived from patients, α4β2 nicotinic receptor patterns that correlated with CAMCOGtotal (r=−0.52, p=0.04), MMSE (r=−0.68, p=0.01) and CAMCOGmemory (r=−0.70, p=0.01), demonstrating a common ‘cognitive’ topography of relative decreased binding in lateral/medial prefrontal, lateral temporal, inferior parietal and thalamus along with relative preserved/increased binding in cingulate, insula, occipital and medial temporal regions, structures representing a range of networks supporting executive, language, social cognition, attention and sensory functions.

Conclusion: In conclusion, disease and cognitive related patterns of cholinergic α4β2 nicotinic receptor binding were apparent in DLB and could inform future therapeutic targets of these receptors in this condition.

Type
Research
Information
BJPsych Open , Volume 11 , Supplement S1: Abstracts from the RCPsych International Congress 2025, 23–26 June , June 2025 , pp. S37
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Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of Royal College of Psychiatrists

Footnotes

Abstracts were reviewed by the RCPsych Academic Faculty rather than by the standard BJPsych Open peer review process and should not be quoted as peer-reviewed by BJPsych Open in any subsequent publication.

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