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Cholinergic and perfusion brain networks in Parkinson disease dementia

View Article: PubMed Central - PubMed

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 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.

No MeSH data available.


Related in: MedlinePlus

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.
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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.

Mentions: The SCPQNB that distinguished PDD from controls is shown in figure 1, A and B. SSFQNB scores were higher in PDD than controls (mean ± SD; controls = 1.5 ± 2.5, PDD = 6.2 ± 3.3, F1,47 = 31.9, p < 0.001; figure 1C). The pattern was mainly characterized by concomitant decreases in M1/M4 binding (blue regions) in basal forebrain, temporal, striatal, insula, and anterior cingulate together with concomitant preserved or increases (red regions) in frontal and parieto-occipital areas. Table e-1 on the Neurology® Web site at Neurology.org presents detailed description of specific regions contributing to the M1/M4 disease-related pattern.


Cholinergic and perfusion brain networks in Parkinson disease dementia
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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940066&req=5

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.
Mentions: The SCPQNB that distinguished PDD from controls is shown in figure 1, A and B. SSFQNB scores were higher in PDD than controls (mean ± SD; controls = 1.5 ± 2.5, PDD = 6.2 ± 3.3, F1,47 = 31.9, p < 0.001; figure 1C). The pattern was mainly characterized by concomitant decreases in M1/M4 binding (blue regions) in basal forebrain, temporal, striatal, insula, and anterior cingulate together with concomitant preserved or increases (red regions) in frontal and parieto-occipital areas. Table e-1 on the Neurology® Web site at Neurology.org presents detailed description of specific regions contributing to the M1/M4 disease-related pattern.

View Article: PubMed Central - PubMed

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 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 &lt; 0.001) in cholinesterase inhibitor&ndash;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 &lt; 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.

No MeSH data available.


Related in: MedlinePlus