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. 2016 Jul 12;87(2):178-85.
doi: 10.1212/WNL.0000000000002839. Epub 2016 Jun 15.

Cholinergic and perfusion brain networks in Parkinson disease dementia

Sean J Colloby  1 , Ian G McKeith  2 , David J Burn  2 , David J Wyper  2 , John T O'Brien  2 , John-Paul Taylor  2
Affiliations

Cholinergic and perfusion brain networks in Parkinson disease dementia

Sean J Colloby et al. Neurology. .

Abstract

Objective: To investigate muscarinic M1/M4 cholinergic networks in Parkinson disease dementia (PDD) and their association with changes in Mini-Mental State Examination (MMSE) after 12 weeks of treatment with donepezil.

Methods: Forty-nine participants (25 PDD and 24 elderly controls) underwent (123)I-QNB and (99m)Tc-exametazime SPECT scanning. We implemented voxel principal components (PC) analysis, producing a series of PC images of patterns of interrelated voxels across individuals. Linear regression analyses derived specific M1/M4 and perfusion spatial covariance patterns (SCPs).

Results: We found an M1/M4 SCP of relative decreased binding in basal forebrain, temporal, striatum, insula, and anterior cingulate (F1,47 = 31.9, p < 0.001) in cholinesterase inhibitor-naive patients with PDD, implicating limbic-paralimbic and salience cholinergic networks. The corresponding regional cerebral blood flow SCP showed relative decreased uptake in temporoparietal and prefrontal areas (F1,47 = 177.5, p < 0.001) and nodes of the frontoparietal and default mode networks (DMN). The M1/M4 pattern that correlated with an improvement in MMSE (r = 0.58, p = 0.005) revealed relatively preserved/increased pre/medial/orbitofrontal, parietal, and posterior cingulate areas coinciding with the DMN and frontoparietal networks.

Conclusion: Dysfunctional limbic-paralimbic and salience cholinergic networks were associated with PDD. Established cholinergic maintenance of the DMN and frontoparietal networks may be prerequisite for cognitive remediation following cholinergic treatment in this condition.

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Figures

Figure 1
Figure 1. Muscarinic M1/M4 spatial covariance pattern in Parkinson disease dementia (PDD)
Disease-related M1/M4 spatial covariance pattern in PDD projected onto orthogonal (A) and rendered (B) displays of the QNB template. Distribution of subject scaling factor (SSFQNB) scores across groups (C). Ant = anterior; Pos = posterior; Sup = superior.
Figure 2
Figure 2. Regional cerebral blood flow (rCBF) spatial covariance pattern in Parkinson disease dementia (PDD)
Disease-related rCBF spatial covariance pattern in PDD projected onto orthogonal (A) and rendered (B) displays of the rCBF template. Distribution of subject scaling factor (SSFrCBF) scores across groups (C). Ant = anterior; Pos = posterior; Sup = superior.
Figure 3
Figure 3. M1/M4 spatial covariance pattern (SCP) ∆ Mini-Mental State Examination (MMSE) in Parkinson disease dementia (PDD) (n = 18)
(A–C) M1/M4 SCP in PDD (n = 18) that correlated with ∆MMSErel_b.
See this image and copyright information in PMC

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