Cholinergic and perfusion brain networks in Parkinson disease dementia

  1. Lookup NU author(s)
  2. Dr Sean Colloby
  3. Professor Ian McKeith
  4. Professor David Burn
  5. Professor John O'Brien
  6. Dr John-Paul Taylor
Author(s)Colloby SJ, McKeith IG, Burn DJ, Wyper DJ, O'Brien JT, Taylor JP
Publication type Article
ISSN (print)0028-3878
ISSN (electronic)1526-632X
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OBJECTIVE: To investigate muscarinic M1/M4 cholinergicnetworks 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 cholinergicnetworks. 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 cholinergicnetworks 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.
PublisherLippincott Williams & Wilkins, Ltd.
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