MovDisordV3, Ncbi, Merge, bibRecord, 004019

Extra-nigral pathologies are common in Parkinson disease with freezing of gait: an in vivo PET study

Identifieur interne : 004019 ( Ncbi/Merge ); précédent : 004018; suivant : 004020

Extra-nigral pathologies are common in Parkinson disease with freezing of gait: an in vivo PET study

Auteurs : Nicolaas I. Bohnen [États-Unis] ; Kirk A. Frey [États-Unis] ; Stephanie Studenski [États-Unis] ; Vikas Kotagal [États-Unis] ; Robert A. Koeppe [États-Unis] ; Gregory M. Constantine [États-Unis] ; Peter J. H. Scott [États-Unis] ; Roger L. Albin [États-Unis] ; Martijn L. T. M Müller [États-Unis]

Source :

Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2014.

RBID : PMC:4162130

English descriptors

KwdEn :
- Acetylcholinesterase (metabolism), Aged, Aged, 80 and over, Amyloid beta-Peptides (metabolism), Benzothiazoles (diagnostic use), Carbon Isotopes (diagnostic use), Cross-Sectional Studies, Female, Freezing Reaction, Cataleptic (physiology), Gait Disorders, Neurologic (etiology), Gait Disorders, Neurologic (radionuclide imaging), Humans, Magnetic Resonance Imaging, Male, Middle Aged, Parkinson Disease (complications), Positron-Emission Tomography, Substantia Nigra (pathology), Tetrabenazine (analogs & derivatives), Tetrabenazine (diagnostic use), Vesicular Monoamine Transport Proteins (metabolism).
MESH :
- chemical , analogs & derivatives : Tetrabenazine.
- chemical , diagnostic use : Benzothiazoles, Carbon Isotopes, Tetrabenazine.
- chemical , metabolism : Acetylcholinesterase, Amyloid beta-Peptides, Vesicular Monoamine Transport Proteins.
- complications : Parkinson Disease.
- etiology : Gait Disorders, Neurologic.
- pathology : Substantia Nigra.
- physiology : Freezing Reaction, Cataleptic.
- radionuclide imaging : Gait Disorders, Neurologic.
- Aged, Aged, 80 and over, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Positron-Emission Tomography.

Abstract

BACKGROUND

Cholinergic denervation has been associated with falls and slower gait speed and β-amyloid deposition with greater severity of axial motor impairments in Parkinson disease (PD). However, little is known about the association between the presence of extra-nigral pathologies and freezing of gait (FoG).

METHODS

Patients with PD (n=143; age 65.5±7.4 years, Hoehn and Yahr stage 2.4±0.6, Montreal Cognitive Assessment score 25.9±2.6) underwent [¹¹C]methyl-4-pi-peridinyl propionate acetylcholinesterase and [¹¹C]dihydrotetrabenazine dopaminergic PET imaging, and clinical, including FoG, assessment in the dopaminergic “off” state. A subset of subjects (n=61) underwent [¹¹C]Pittsburgh compound-B β-amyloid PET imaging. Normative data were used to dichotomize abnormal β-amyloid uptake or cholinergic deficits.

RESULTS

FoG was present in 20 patients (14.0%). Freezers had longer duration of disease (P=0.009), more severe motor disease (P<0.0001) and lower striatal dopaminergic activity (P=0.013) compared to non-freezers. FoG was more common in patients with diminished neocortical cholinergic innervation (23.9%, χ²=5.56, P=0.018) but not in the thalamic cholinergic denervation group (17.4%, χ²=0.26, P=0.61). Subgroup analysis showed higher frequency of FoG with increased neocortical β-amyloid deposition (30.4%, Fisher Exact test: P = 0.032). FoG frequency was lowest with absence of both pathology (4.8%), intermediate in subjects with single extra-nigral pathology (14.3%) and highest with combined neocortical cholinopathy and amyloidopathy (41.7%; Cochran-Armitage trend test Z=2.63, P=0.015). Within the group of freezers, 90% had at least one of the two extra-nigral pathologies studied.

CONCLUSIONS

Extra-nigral pathologies, in particular the combined presence of cortical cholinopathy and amyloidopathy, are common in PD with FoG and may contribute to its pathophysiology.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162130

DOI: 10.1002/mds.25929
PubMed: 24909584
PubMed Central: 4162130

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PMC:4162130

Le document en format XML

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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acetylcholinesterase (metabolism)</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Amyloid beta-Peptides (metabolism)</term>
<term>Benzothiazoles (diagnostic use)</term>
<term>Carbon Isotopes (diagnostic use)</term>
<term>Cross-Sectional Studies</term>
<term>Female</term>
<term>Freezing Reaction, Cataleptic (physiology)</term>
<term>Gait Disorders, Neurologic (etiology)</term>
<term>Gait Disorders, Neurologic (radionuclide imaging)</term>
<term>Humans</term>
<term>Magnetic Resonance Imaging</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Parkinson Disease (complications)</term>
<term>Positron-Emission Tomography</term>
<term>Substantia Nigra (pathology)</term>
<term>Tetrabenazine (analogs & derivatives)</term>
<term>Tetrabenazine (diagnostic use)</term>
<term>Vesicular Monoamine Transport Proteins (metabolism)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Tetrabenazine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="diagnostic use" xml:lang="en"><term>Benzothiazoles</term>
<term>Carbon Isotopes</term>
<term>Tetrabenazine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Acetylcholinesterase</term>
<term>Amyloid beta-Peptides</term>
<term>Vesicular Monoamine Transport Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Gait Disorders, Neurologic</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Substantia Nigra</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Freezing Reaction, Cataleptic</term>
</keywords>
<keywords scheme="MESH" qualifier="radionuclide imaging" xml:lang="en"><term>Gait Disorders, Neurologic</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Aged</term>
<term>Aged, 80 and over</term>
<term>Cross-Sectional Studies</term>
<term>Female</term>
<term>Humans</term>
<term>Magnetic Resonance Imaging</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Positron-Emission Tomography</term>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>BACKGROUND</title>
<p id="P1">Cholinergic denervation has been associated with falls and slower gait speed and β-amyloid deposition with greater severity of axial motor impairments in Parkinson disease (PD). However, little is known about the association between the presence of extra-nigral pathologies and freezing of gait (FoG).</p>
</sec>
<sec id="S2"><title>METHODS</title>
<p id="P2">Patients with PD (n=143; age 65.5±7.4 years, Hoehn and Yahr stage 2.4±0.6, Montreal Cognitive Assessment score 25.9±2.6) underwent [<sup>11</sup>
C]methyl-4-pi-peridinyl propionate acetylcholinesterase and [<sup>11</sup>
C]dihydrotetrabenazine dopaminergic PET imaging, and clinical, including FoG, assessment in the dopaminergic “off” state. A subset of subjects (n=61) underwent [<sup>11</sup>
C]Pittsburgh compound-B β-amyloid PET imaging. Normative data were used to dichotomize abnormal β-amyloid uptake or cholinergic deficits.</p>
</sec>
<sec id="S3"><title>RESULTS</title>
<p id="P3">FoG was present in 20 patients (14.0%). Freezers had longer duration of disease (P=0.009), more severe motor disease (P<0.0001) and lower striatal dopaminergic activity (P=0.013) compared to non-freezers. FoG was more common in patients with diminished neocortical cholinergic innervation (23.9%, χ<sup>2</sup>
=5.56, P=0.018) but not in the thalamic cholinergic denervation group (17.4%, χ<sup>2</sup>
=0.26, P=0.61). Subgroup analysis showed higher frequency of FoG with increased neocortical β-amyloid deposition (30.4%, Fisher Exact test: P = 0.032). FoG frequency was lowest with absence of both pathology (4.8%), intermediate in subjects with single extra-nigral pathology (14.3%) and highest with combined neocortical cholinopathy and amyloidopathy (41.7%; Cochran-Armitage trend test Z=2.63, P=0.015). Within the group of freezers, 90% had at least one of the two extra-nigral pathologies studied.</p>
</sec>
<sec id="S4"><title>CONCLUSIONS</title>
<p id="P4">Extra-nigral pathologies, in particular the combined presence of cortical cholinopathy and amyloidopathy, are common in PD with FoG and may contribute to its pathophysiology.</p>
</sec>
</div>
</front>
</TEI>
<double pmid="24909584"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Extra-nigral pathologies are common in Parkinson disease with freezing of gait: an <italic>in vivo</italic>
 PET study</title>
<author><name sortKey="Bohnen, Nicolaas I" sort="Bohnen, Nicolaas I" uniqKey="Bohnen N" first="Nicolaas I." last="Bohnen">Nicolaas I. Bohnen</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A3">Neurology Service and GRECC, VAAAHS, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Neurology Service and GRECC, VAAAHS, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Frey, Kirk A" sort="Frey, Kirk A" uniqKey="Frey K" first="Kirk A." last="Frey">Kirk A. Frey</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Studenski, Stephanie" sort="Studenski, Stephanie" uniqKey="Studenski S" first="Stephanie" last="Studenski">Stephanie Studenski</name>
<affiliation wicri:level="4"><nlm:aff id="A4">Division of Geriatrics, Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA and Pittsburgh VA GRECC, Pittsburgh, PA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Geriatrics, Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA and Pittsburgh VA GRECC, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
<settlement type="city">Pittsburgh</settlement>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
</author>
<author><name sortKey="Kotagal, Vikas" sort="Kotagal, Vikas" uniqKey="Kotagal V" first="Vikas" last="Kotagal">Vikas Kotagal</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Koeppe, Robert A" sort="Koeppe, Robert A" uniqKey="Koeppe R" first="Robert A" last="Koeppe">Robert A. Koeppe</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Constantine, Gregory M" sort="Constantine, Gregory M" uniqKey="Constantine G" first="Gregory M." last="Constantine">Gregory M. Constantine</name>
<affiliation wicri:level="4"><nlm:aff id="A5">Departments of Mathematics and Statistics, University of Pittsburgh, Pittsburgh, PA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Mathematics and Statistics, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
<settlement type="city">Pittsburgh</settlement>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
</author>
<author><name sortKey="Scott, Peter J H" sort="Scott, Peter J H" uniqKey="Scott P" first="Peter J. H." last="Scott">Peter J. H. Scott</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Albin, Roger L" sort="Albin, Roger L" uniqKey="Albin R" first="Roger L." last="Albin">Roger L. Albin</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A3">Neurology Service and GRECC, VAAAHS, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Neurology Service and GRECC, VAAAHS, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A6">Michigan Alzheimer Disease Center, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Michigan Alzheimer Disease Center, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Muller, Martijn L T M" sort="Muller, Martijn L T M" uniqKey="Muller M" first="Martijn L. T. M" last="Müller">Martijn L. T. M Müller</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">24909584</idno>
<idno type="pmc">4162130</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162130</idno>
<idno type="RBID">PMC:4162130</idno>
<idno type="doi">10.1002/mds.25929</idno>
<date when="2014">2014</date>
<idno type="wicri:Area/Pmc/Corpus">000408</idno>
<idno type="wicri:Area/Pmc/Curation">000408</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000035</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Extra-nigral pathologies are common in Parkinson disease with freezing of gait: an <italic>in vivo</italic>
 PET study</title>
<author><name sortKey="Bohnen, Nicolaas I" sort="Bohnen, Nicolaas I" uniqKey="Bohnen N" first="Nicolaas I." last="Bohnen">Nicolaas I. Bohnen</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A3">Neurology Service and GRECC, VAAAHS, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Neurology Service and GRECC, VAAAHS, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Frey, Kirk A" sort="Frey, Kirk A" uniqKey="Frey K" first="Kirk A." last="Frey">Kirk A. Frey</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Studenski, Stephanie" sort="Studenski, Stephanie" uniqKey="Studenski S" first="Stephanie" last="Studenski">Stephanie Studenski</name>
<affiliation wicri:level="4"><nlm:aff id="A4">Division of Geriatrics, Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA and Pittsburgh VA GRECC, Pittsburgh, PA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Geriatrics, Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA and Pittsburgh VA GRECC, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
<settlement type="city">Pittsburgh</settlement>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
</author>
<author><name sortKey="Kotagal, Vikas" sort="Kotagal, Vikas" uniqKey="Kotagal V" first="Vikas" last="Kotagal">Vikas Kotagal</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Koeppe, Robert A" sort="Koeppe, Robert A" uniqKey="Koeppe R" first="Robert A" last="Koeppe">Robert A. Koeppe</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Constantine, Gregory M" sort="Constantine, Gregory M" uniqKey="Constantine G" first="Gregory M." last="Constantine">Gregory M. Constantine</name>
<affiliation wicri:level="4"><nlm:aff id="A5">Departments of Mathematics and Statistics, University of Pittsburgh, Pittsburgh, PA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Mathematics and Statistics, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
<settlement type="city">Pittsburgh</settlement>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
</author>
<author><name sortKey="Scott, Peter J H" sort="Scott, Peter J H" uniqKey="Scott P" first="Peter J. H." last="Scott">Peter J. H. Scott</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Albin, Roger L" sort="Albin, Roger L" uniqKey="Albin R" first="Roger L." last="Albin">Roger L. Albin</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A3">Neurology Service and GRECC, VAAAHS, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Neurology Service and GRECC, VAAAHS, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A6">Michigan Alzheimer Disease Center, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Michigan Alzheimer Disease Center, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Muller, Martijn L T M" sort="Muller, Martijn L T M" uniqKey="Muller M" first="Martijn L. T. M" last="Müller">Martijn L. T. M Müller</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
<idno type="ISSN">0885-3185</idno>
<idno type="eISSN">1531-8257</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>BACKGROUND</title>
<p id="P1">Cholinergic denervation has been associated with falls and slower gait speed and β-amyloid deposition with greater severity of axial motor impairments in Parkinson disease (PD). However, little is known about the association between the presence of extra-nigral pathologies and freezing of gait (FoG).</p>
</sec>
<sec id="S2"><title>METHODS</title>
<p id="P2">Patients with PD (n=143; age 65.5±7.4 years, Hoehn and Yahr stage 2.4±0.6, Montreal Cognitive Assessment score 25.9±2.6) underwent [<sup>11</sup>
C]methyl-4-pi-peridinyl propionate acetylcholinesterase and [<sup>11</sup>
C]dihydrotetrabenazine dopaminergic PET imaging, and clinical, including FoG, assessment in the dopaminergic “off” state. A subset of subjects (n=61) underwent [<sup>11</sup>
C]Pittsburgh compound-B β-amyloid PET imaging. Normative data were used to dichotomize abnormal β-amyloid uptake or cholinergic deficits.</p>
</sec>
<sec id="S3"><title>RESULTS</title>
<p id="P3">FoG was present in 20 patients (14.0%). Freezers had longer duration of disease (P=0.009), more severe motor disease (P<0.0001) and lower striatal dopaminergic activity (P=0.013) compared to non-freezers. FoG was more common in patients with diminished neocortical cholinergic innervation (23.9%, χ<sup>2</sup>
=5.56, P=0.018) but not in the thalamic cholinergic denervation group (17.4%, χ<sup>2</sup>
=0.26, P=0.61). Subgroup analysis showed higher frequency of FoG with increased neocortical β-amyloid deposition (30.4%, Fisher Exact test: P = 0.032). FoG frequency was lowest with absence of both pathology (4.8%), intermediate in subjects with single extra-nigral pathology (14.3%) and highest with combined neocortical cholinopathy and amyloidopathy (41.7%; Cochran-Armitage trend test Z=2.63, P=0.015). Within the group of freezers, 90% had at least one of the two extra-nigral pathologies studied.</p>
</sec>
<sec id="S4"><title>CONCLUSIONS</title>
<p id="P4">Extra-nigral pathologies, in particular the combined presence of cortical cholinopathy and amyloidopathy, are common in PD with FoG and may contribute to its pathophysiology.</p>
</sec>
</div>
</front>
</TEI>
</pmc>
<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Extra-nigral pathological conditions are common in Parkinson's disease with freezing of gait: an in vivo positron emission tomography study.</title>
<author><name sortKey="Bohnen, Nicolaas I" sort="Bohnen, Nicolaas I" uniqKey="Bohnen N" first="Nicolaas I" last="Bohnen">Nicolaas I. Bohnen</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Neurology Service and GRECC, VAAAHS, Ann Arbor, MI, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Neurology Service and GRECC, VAAAHS, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Frey, Kirk A" sort="Frey, Kirk A" uniqKey="Frey K" first="Kirk A" last="Frey">Kirk A. Frey</name>
</author>
<author><name sortKey="Studenski, Stephanie" sort="Studenski, Stephanie" uniqKey="Studenski S" first="Stephanie" last="Studenski">Stephanie Studenski</name>
</author>
<author><name sortKey="Kotagal, Vikas" sort="Kotagal, Vikas" uniqKey="Kotagal V" first="Vikas" last="Kotagal">Vikas Kotagal</name>
</author>
<author><name sortKey="Koeppe, Robert A" sort="Koeppe, Robert A" uniqKey="Koeppe R" first="Robert A" last="Koeppe">Robert A. Koeppe</name>
</author>
<author><name sortKey="Constantine, Gregory M" sort="Constantine, Gregory M" uniqKey="Constantine G" first="Gregory M" last="Constantine">Gregory M. Constantine</name>
</author>
<author><name sortKey="Scott, Peter J H" sort="Scott, Peter J H" uniqKey="Scott P" first="Peter J H" last="Scott">Peter J H. Scott</name>
</author>
<author><name sortKey="Albin, Roger L" sort="Albin, Roger L" uniqKey="Albin R" first="Roger L" last="Albin">Roger L. Albin</name>
</author>
<author><name sortKey="Muller, Martijn L T M" sort="Muller, Martijn L T M" uniqKey="Muller M" first="Martijn L T M" last="Müller">Martijn L T M. Müller</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2014">2014</date>
<idno type="RBID">pubmed:24909584</idno>
<idno type="pmid">24909584</idno>
<idno type="doi">10.1002/mds.25929</idno>
<idno type="wicri:Area/PubMed/Corpus">000480</idno>
<idno type="wicri:Area/PubMed/Curation">000480</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000600</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Extra-nigral pathological conditions are common in Parkinson's disease with freezing of gait: an in vivo positron emission tomography study.</title>
<author><name sortKey="Bohnen, Nicolaas I" sort="Bohnen, Nicolaas I" uniqKey="Bohnen N" first="Nicolaas I" last="Bohnen">Nicolaas I. Bohnen</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Neurology Service and GRECC, VAAAHS, Ann Arbor, MI, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Neurology Service and GRECC, VAAAHS, Ann Arbor, MI</wicri:regionArea>
<placeName><region type="state">Michigan</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Frey, Kirk A" sort="Frey, Kirk A" uniqKey="Frey K" first="Kirk A" last="Frey">Kirk A. Frey</name>
</author>
<author><name sortKey="Studenski, Stephanie" sort="Studenski, Stephanie" uniqKey="Studenski S" first="Stephanie" last="Studenski">Stephanie Studenski</name>
</author>
<author><name sortKey="Kotagal, Vikas" sort="Kotagal, Vikas" uniqKey="Kotagal V" first="Vikas" last="Kotagal">Vikas Kotagal</name>
</author>
<author><name sortKey="Koeppe, Robert A" sort="Koeppe, Robert A" uniqKey="Koeppe R" first="Robert A" last="Koeppe">Robert A. Koeppe</name>
</author>
<author><name sortKey="Constantine, Gregory M" sort="Constantine, Gregory M" uniqKey="Constantine G" first="Gregory M" last="Constantine">Gregory M. Constantine</name>
</author>
<author><name sortKey="Scott, Peter J H" sort="Scott, Peter J H" uniqKey="Scott P" first="Peter J H" last="Scott">Peter J H. Scott</name>
</author>
<author><name sortKey="Albin, Roger L" sort="Albin, Roger L" uniqKey="Albin R" first="Roger L" last="Albin">Roger L. Albin</name>
</author>
<author><name sortKey="Muller, Martijn L T M" sort="Muller, Martijn L T M" uniqKey="Muller M" first="Martijn L T M" last="Müller">Martijn L T M. Müller</name>
</author>
</analytic>
<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
<idno type="eISSN">1531-8257</idno>
<imprint><date when="2014" type="published">2014</date>
</imprint>
</series>
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</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acetylcholinesterase (metabolism)</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Amyloid beta-Peptides (metabolism)</term>
<term>Benzothiazoles (diagnostic use)</term>
<term>Carbon Isotopes (diagnostic use)</term>
<term>Cross-Sectional Studies</term>
<term>Female</term>
<term>Freezing Reaction, Cataleptic (physiology)</term>
<term>Gait Disorders, Neurologic (etiology)</term>
<term>Gait Disorders, Neurologic (radionuclide imaging)</term>
<term>Humans</term>
<term>Magnetic Resonance Imaging</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Parkinson Disease (complications)</term>
<term>Positron-Emission Tomography</term>
<term>Substantia Nigra (pathology)</term>
<term>Tetrabenazine (analogs & derivatives)</term>
<term>Tetrabenazine (diagnostic use)</term>
<term>Vesicular Monoamine Transport Proteins (metabolism)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Tetrabenazine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="diagnostic use" xml:lang="en"><term>Benzothiazoles</term>
<term>Carbon Isotopes</term>
<term>Tetrabenazine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Acetylcholinesterase</term>
<term>Amyloid beta-Peptides</term>
<term>Vesicular Monoamine Transport Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Gait Disorders, Neurologic</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Substantia Nigra</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Freezing Reaction, Cataleptic</term>
</keywords>
<keywords scheme="MESH" qualifier="radionuclide imaging" xml:lang="en"><term>Gait Disorders, Neurologic</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Aged</term>
<term>Aged, 80 and over</term>
<term>Cross-Sectional Studies</term>
<term>Female</term>
<term>Humans</term>
<term>Magnetic Resonance Imaging</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Positron-Emission Tomography</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Cholinergic denervation has been associated with falls and slower gait speed and β-amyloid deposition with greater severity of axial motor impairments in Parkinson disease (PD). However, little is known about the association between the presence of extra-nigral pathological conditions and freezing of gait (FoG). Patients with PD (n = 143; age, 65.5 ± 7.4 years, Hoehn and Yahr stage, 2.4 ± 0.6; Montreal Cognitive Assessment score, 25.9 ± 2.6) underwent [(11) C]methyl-4-piperidinyl propionate acetylcholinesterase and [(11) C]dihydrotetrabenazine dopaminergic PET imaging, and clinical, including FoG, assessment in the dopaminergic "off" state. A subset of subjects (n = 61) underwent [(11) C]Pittsburgh compound-B β-amyloid positron emission tomography (PET) imaging. Normative data were used to dichotomize abnormal β-amyloid uptake or cholinergic deficits. Freezing of gait was present in 20 patients (14.0%). Freezers had longer duration of disease (P = 0.009), more severe motor disease (P < 0.0001), and lower striatal dopaminergic activity (P = 0.013) compared with non-freezers. Freezing of gait was more common in patients with diminished neocortical cholinergic innervation (23.9%, χ(2)  = 5.56, P = 0.018), but not in the thalamic cholinergic denervation group (17.4%, χ(2)  = 0.26, P = 0.61). Subgroup analysis showed higher frequency of FoG with increased neocortical β-amyloid deposition (30.4%, Fisher Exact test: P = 0.032). Frequency of FoG was lowest with absence of both pathological conditions (4.8%), intermediate in subjects with single extra-nigral pathological condition (14.3%), and highest with combined neocortical cholinopathy and amyloidopathy (41.7%; Cochran-Armitage trend test, Z = 2.63, P = 0.015). Within the group of freezers, 90% had at least one of the two extra-nigral pathological conditions studied. Extra-nigral pathological conditions, in particular the combined presence of cortical cholinopathy and amyloidopathy, are common in PD with FoG and may contribute to its pathophysiology. © 2014 International Parkinson and Movement Disorder Society.</div>
</front>
</TEI>
</pubmed>
</double>
</record>

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	Movement Disorders (revue)
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Movement Disorders (revue)

Extra-nigral pathologies are common in Parkinson disease with freezing of gait: an in vivo PET study

Extra-nigral pathologies are common in Parkinson disease with freezing of gait: an in vivo PET study

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