Open AccessCholinergic muscarinic M1/M4 receptor networks in dementia with Lewy bodies
Author(s) -
Sean J. Colloby,
Pradeep J. Nathan,
Ian McKeith,
Geor Bakker,
John O’Brien,
JohnPaul Taylor
Publication year - 2020
Publication title -
brain communications
Language(s) - English
Resource type - Journals
ISSN - 2632-1297
DOI - 10.1093/braincomms/fcaa098
Subject(s) - dementia with lewy bodies , neuroscience , psychology , precuneus , cholinergic , medicine , muscarinic acetylcholine receptor m1 , dementia , muscarinic acetylcholine receptor , audiology , cognition , receptor , disease
Cholinergic dysfunction is central in dementia with Lewy bodies, possibly contributing to the cognitive and psychiatric phenotypes of this condition. We investigated baseline muscarinic M 1 /M 4 receptor spatial covariance patterns in dementia with Lewy bodies and their association with changes in cognition and neuropsychiatric symptoms after 12 weeks of treatment with the cholinesterase inhibitor donepezil. Thirty-eight participants (14 cholinesterase inhibitor naive patients, 24 healthy older individuals) underwent 123 I-iodo-quinuclidinyl-benzilate (M 1 /M 4 receptor assessment) and 99m Tc-exametazime (perfusion) single-photon emission computed tomography scanning. We implemented voxel principal components analysis, producing a series of images representing patterns of inter-correlated voxels across individuals. Linear regression analyses derived specific M 1 /M 4 and perfusion spatial covariance patterns associated with patients. A discreet M 1 /M 4 pattern that distinguished patients from controls (W 1,19.7 = 16.7, P = 0.001), showed relative decreased binding in right lateral temporal and insula, as well as relative preserved/increased binding in frontal, precuneus, lingual and cuneal regions, implicating nodes within attention and dorsal visual networks. We then derived from patients an M 1 /M 4 pattern that correlated with a positive change in mini-mental state examination ( r = 0.52, P = 0.05), showing relative preserved/increased uptake in prefrontal, temporal pole and anterior cingulate, elements of attention-related networks. We also generated from patients an M 1 /M 4 pattern that correlated with a positive change in neuropsychiatric inventory score ( r = 0.77, P = 0.002), revealing relative preserved/increased uptake within a bilateral temporal-precuneal-striatal system. Although in a small sample and therefore tentative, we posit that optimal response of donepezil on cognitive and neuropsychiatric signs in patients with dementia with Lewy bodies were associated with a maintenance of muscarinic M 1 /M 4 receptor expression within attentional/executive and ventral visual network hubs, respectively.