PT  - JOURNAL ARTICLE
AU  - Sean J. Colloby
AU  - Ian G. McKeith
AU  - David J. Burn
AU  - David J. Wyper
AU  - John T. O'Brien
AU  - John-Paul Taylor
TI  - Cholinergic and perfusion brain networks in Parkinson disease dementia
AID  - 10.1212/WNL.0000000000002839
DP  - 2016 Jul 12
TA  - Neurology
PG  - 178--185
VI  - 87
IP  - 2
4099  - http://n.neurology.org/content/87/2/178.short
4100  - http://n.neurology.org/content/87/2/178.full
SO  - Neurology2016 Jul 12; 87
AB  - 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 123I-QNB and 99mTc-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.AIC=Akaike information criterion; CAMCOG=Cambridge Cognitive Examination; CAMCOGexec=Cambridge Cognitive Examination executive function subscale; CAMCOGmemory=Cambridge Cognitive Examination memory subscale; ChEI=cholinesterase inhibitor; DLB=dementia with Lewy bodies; DMN=default mode network; MMSE=Mini-Mental State Examination; NBM=nuclear basalis of Meynert; NPI=Neuropsychiatric Inventory; PC=principal component; PD=Parkinson disease; PDD=Parkinson disease dementia; rCBF=regional cerebral blood flow; SCP=spatial covariance pattern; SN=salience network; SSF=subject scaling factor