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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

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.
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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.

Mentions: Summary data for the donepezil-treated group are shown (table 2). During the observation period, differences in MMSE were identified between baseline and 12-week scores (p < 0.001). The resultant SCP∆MMSE is presented in figure 3, A and B, while figure 3C depicts SSF∆MMSE plotted as a function of ∆MMSErel_b. The pattern consists of concurrent decreases in M1/M4 binding (blue) in fusiform, anterior cingulate, lingual gyrus, and precentral areas with concurrent preserved or increases (red) in pre/medial/orbitofrontal, parietal, and posterior cingulate regions. Details of specific regions participating in the pattern are supplied (table e-3).


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

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

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.
Mentions: Summary data for the donepezil-treated group are shown (table 2). During the observation period, differences in MMSE were identified between baseline and 12-week scores (p < 0.001). The resultant SCP∆MMSE is presented in figure 3, A and B, while figure 3C depicts SSF∆MMSE plotted as a function of ∆MMSErel_b. The pattern consists of concurrent decreases in M1/M4 binding (blue) in fusiform, anterior cingulate, lingual gyrus, and precentral areas with concurrent preserved or increases (red) in pre/medial/orbitofrontal, parietal, and posterior cingulate regions. Details of specific regions participating in the pattern are supplied (table e-3).

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