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Regional covariance of muscarinic acetylcholine receptors in Alzheimer's disease using (R, R) [123I]-QNB SPECT

Lookup NU author(s): Dr Sean Colloby, Professor Ian McKeith, Professor John O'Brien, Professor John-Paul Taylor

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Abstract

Alzheimer's disease (AD) is characterised by deficits in cholinergic neurotransmission and subsequent receptor changes. We investigated (123)I-iodo-quinuclidinyl-benzilate (QNB) SPECT images using spatial covariance analysis (SCA), to detect an M1/M4 receptor spatial covariance pattern (SCP) that distinguished AD from controls. Furthermore, a corresponding regional cerebral blood flow (rCBF) SCP was also derived. Thirty-nine subjects (15 AD and 24 healthy elderly controls) underwent (123)I-QNB and (99m)Tc-exametazime SPECT. Voxel SCA was simultaneously applied to the set of smoothed/registered scans, generating a series of eigenimages representing common intercorrelated voxels across subjects. Linear regression identified individual M1/M4 and rCBF SCPs that discriminated AD from controls. The M1/M4 SCP showed concomitant decreased uptake in medial temporal, inferior frontal, basal forebrain and cingulate relative to concomitant increased uptake in frontal poles, occipital, pre-post central and precuneus/superior parietal regions (F 1,37 = 85.7, p < 0.001). A largely different perfusion SCP was obtained showing concomitant decreased rCBF in medial and superior temporal, precuneus, inferior parietal and cingulate relative to concomitant increased rCBF in cerebellum, pre-post central, putamen, fusiform and brain stem/midbrain regions (F 1,37 = 77.5, p < 0.001). The M1/M4 SCP expression correlated with the duration of cognitive symptoms (r = 0.90, p < 0.001), whereas the rCBF SCP expression negatively correlated with MMSE, CAMCOG and CAMCOGmemory (r ≥ |0.63|, p ≤ 0.006). (123)I-QNB SPECT revealed an M1/M4 basocortical covariance pattern, distinct from rCBF, reflecting the duration of disease rather than current clinical symptoms. This approach could be more sensitive than univariate methods in characterising the cholinergic/rCBF changes that underpin the clinical phenotype of AD.


Publication metadata

Author(s): Colloby SJ, McKeith IG, Wyper DJ, O'Brien JT, Taylor JP

Publication type: Article

Publication status: Published

Journal: Journal of Neurology

Year: 2015

Volume: 262

Issue: 9

Pages: 2144-2153

Print publication date: 01/09/2015

Online publication date: 30/06/2015

Acceptance date: 13/06/2015

ISSN (print): 0340-5354

ISSN (electronic): 1432-1459

Publisher: Springer

URL: http://dx.doi.org/10.1007/s00415-015-7827-z

DOI: 10.1007/s00415-015-7827-z


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