Cholinergic and perfusion brain networks in Parkinson disease dementia.
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.



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).



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.



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.
From the Institute of Neuroscience (S.J.C., I.G.M., D.J.B., J.-P.T.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; SINAPSE (D.J.W.), Institute of Neuroscience and Psychology, University of Glasgow; and Department of Psychiatry (J.T.O.), University of Cambridge, UK. sean.colloby@ncl.ac.uk.
Sean J
SJ
Colloby
From the Institute of Neuroscience (S.J.C., I.G.M., D.J.B., J.-P.T.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; SINAPSE (D.J.W.), Institute of Neuroscience and Psychology, University of Glasgow; and Department of Psychiatry (J.T.O.), University of Cambridge, UK.
Ian G
IG
McKeith
From the Institute of Neuroscience (S.J.C., I.G.M., D.J.B., J.-P.T.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; SINAPSE (D.J.W.), Institute of Neuroscience and Psychology, University of Glasgow; and Department of Psychiatry (J.T.O.), University of Cambridge, UK.
David J
DJ
Burn
From the Institute of Neuroscience (S.J.C., I.G.M., D.J.B., J.-P.T.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; SINAPSE (D.J.W.), Institute of Neuroscience and Psychology, University of Glasgow; and Department of Psychiatry (J.T.O.), University of Cambridge, UK.
David J
DJ
Wyper
From the Institute of Neuroscience (S.J.C., I.G.M., D.J.B., J.-P.T.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; SINAPSE (D.J.W.), Institute of Neuroscience and Psychology, University of Glasgow; and Department of Psychiatry (J.T.O.), University of Cambridge, UK.
John T
JT
O'Brien
From the Institute of Neuroscience (S.J.C., I.G.M., D.J.B., J.-P.T.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; SINAPSE (D.J.W.), Institute of Neuroscience and Psychology, University of Glasgow; and Department of Psychiatry (J.T.O.), University of Cambridge, UK.
John-Paul
JP
Taylor
D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D016014:Linear Models; D008297:Male; D008609:Mental Status Schedule; D015999:Multivariate Analysis; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism; D018697:Nootropic Agents / Q000627:therapeutic use; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*; D010880:Piperidines / Q000627:therapeutic use; D019275:Radiopharmaceuticals; D043643:Receptor, Muscarinic M1; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
D000978:Antiparkinson Agents; C086088:CHRM1 protein, human; C000597933:CHRM4 protein, human; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D019275:Radiopharmaceuticals; D043643:Receptor, Muscarinic M1; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic; D000077265:Donepezil