Dopamine transporter availability reflects gastrointestinal dysautonomia in early Parkinson disease

Research output: Contribution to journalArticle

Abstract

Background: Constipation is a prodromal feature of Parkinson's disease (PD) and the gastrointestinal (GI) tract is implicated in the pathogenesis of PD. However, no studies have demonstrated ante-mortem relationships between nigrostriatal dysfunction and GI dysautonomia in PD. Methods: The Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOPA-AUT) assesses dysautonomia in the multi-center Parkinson's Progression Marker Initiative (PPMI). We used linear mixed-effects models and reliable change indices (RCIs) to examine longitudinal associations between dysautonomia and dopamine transporter (DAT) striatal binding ratios (SBRs) measured by single-photon emission computerized tomography in PPMI participants over four years (n = 397 at baseline). Results: Adjusted mixed-models of longitudinal data showed that constipation—but not orthostatic hypotension or urinary dysfunction—was associated with reduced SBR in both caudate (P < 0.001) and putamen (P = 0.040). In both regions, SBR reductions between baseline and 4-year follow-up were significant and measurable (P < 0.0001), with larger decline and variance in the caudate nucleus. Four-year change in caudate—but not putaminal—SBR was significantly associated with RCI-indicated progression of GI dysautonomia (P = 0.031), but not other types of dysautonomia. These associations remained after adjusting for the use of medications or supplements to control constipation. Consistent with prior PPMI reports, motor impairment progression was not associated with SBR reduction. Conclusions: GI dysautonomia correlates with reductions in DAT availability; constipation is most closely associated with caudate-DAT reduction. Worsening GI-dysautonomia and reduced bowel movements may accompany advancing nigral degeneration or changes in nigrostriatal dopamine function.

Original languageEnglish (US)
JournalParkinsonism and Related Disorders
DOIs
StateAccepted/In press - Jan 1 2018

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Primary Dysautonomias
Dopamine Plasma Membrane Transport Proteins
Parkinson Disease
Corpus Striatum
Constipation
Orthostatic Hypotension
Caudate Nucleus
Putamen
Substantia Nigra
Single-Photon Emission-Computed Tomography
Gastrointestinal Tract
Dopamine

Keywords

  • Autonomic
  • Constipation
  • Dopamine transporter
  • Parkinson disease
  • PPMI

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

@article{dda6fc53f4074ecb90131f4168c763c5,
title = "Dopamine transporter availability reflects gastrointestinal dysautonomia in early Parkinson disease",
abstract = "Background: Constipation is a prodromal feature of Parkinson's disease (PD) and the gastrointestinal (GI) tract is implicated in the pathogenesis of PD. However, no studies have demonstrated ante-mortem relationships between nigrostriatal dysfunction and GI dysautonomia in PD. Methods: The Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOPA-AUT) assesses dysautonomia in the multi-center Parkinson's Progression Marker Initiative (PPMI). We used linear mixed-effects models and reliable change indices (RCIs) to examine longitudinal associations between dysautonomia and dopamine transporter (DAT) striatal binding ratios (SBRs) measured by single-photon emission computerized tomography in PPMI participants over four years (n = 397 at baseline). Results: Adjusted mixed-models of longitudinal data showed that constipation—but not orthostatic hypotension or urinary dysfunction—was associated with reduced SBR in both caudate (P < 0.001) and putamen (P = 0.040). In both regions, SBR reductions between baseline and 4-year follow-up were significant and measurable (P < 0.0001), with larger decline and variance in the caudate nucleus. Four-year change in caudate—but not putaminal—SBR was significantly associated with RCI-indicated progression of GI dysautonomia (P = 0.031), but not other types of dysautonomia. These associations remained after adjusting for the use of medications or supplements to control constipation. Consistent with prior PPMI reports, motor impairment progression was not associated with SBR reduction. Conclusions: GI dysautonomia correlates with reductions in DAT availability; constipation is most closely associated with caudate-DAT reduction. Worsening GI-dysautonomia and reduced bowel movements may accompany advancing nigral degeneration or changes in nigrostriatal dopamine function.",
keywords = "Autonomic, Constipation, Dopamine transporter, Parkinson disease, PPMI",
author = "Hinkle, {Jared T.} and Kate Perepezko and Kelly Mills and Zoltan Mari and Ankur Butala and Dawson, {Ted M} and Alexander Pantelyat and Rosenthal, {Liana Isa Shapiro} and Pontone, {Gregory M}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.parkreldis.2018.08.010",
language = "English (US)",
journal = "Parkinsonism and Related Disorders",
issn = "1353-8020",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Dopamine transporter availability reflects gastrointestinal dysautonomia in early Parkinson disease

AU - Hinkle, Jared T.

AU - Perepezko, Kate

AU - Mills, Kelly

AU - Mari, Zoltan

AU - Butala, Ankur

AU - Dawson, Ted M

AU - Pantelyat, Alexander

AU - Rosenthal, Liana Isa Shapiro

AU - Pontone, Gregory M

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Constipation is a prodromal feature of Parkinson's disease (PD) and the gastrointestinal (GI) tract is implicated in the pathogenesis of PD. However, no studies have demonstrated ante-mortem relationships between nigrostriatal dysfunction and GI dysautonomia in PD. Methods: The Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOPA-AUT) assesses dysautonomia in the multi-center Parkinson's Progression Marker Initiative (PPMI). We used linear mixed-effects models and reliable change indices (RCIs) to examine longitudinal associations between dysautonomia and dopamine transporter (DAT) striatal binding ratios (SBRs) measured by single-photon emission computerized tomography in PPMI participants over four years (n = 397 at baseline). Results: Adjusted mixed-models of longitudinal data showed that constipation—but not orthostatic hypotension or urinary dysfunction—was associated with reduced SBR in both caudate (P < 0.001) and putamen (P = 0.040). In both regions, SBR reductions between baseline and 4-year follow-up were significant and measurable (P < 0.0001), with larger decline and variance in the caudate nucleus. Four-year change in caudate—but not putaminal—SBR was significantly associated with RCI-indicated progression of GI dysautonomia (P = 0.031), but not other types of dysautonomia. These associations remained after adjusting for the use of medications or supplements to control constipation. Consistent with prior PPMI reports, motor impairment progression was not associated with SBR reduction. Conclusions: GI dysautonomia correlates with reductions in DAT availability; constipation is most closely associated with caudate-DAT reduction. Worsening GI-dysautonomia and reduced bowel movements may accompany advancing nigral degeneration or changes in nigrostriatal dopamine function.

AB - Background: Constipation is a prodromal feature of Parkinson's disease (PD) and the gastrointestinal (GI) tract is implicated in the pathogenesis of PD. However, no studies have demonstrated ante-mortem relationships between nigrostriatal dysfunction and GI dysautonomia in PD. Methods: The Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOPA-AUT) assesses dysautonomia in the multi-center Parkinson's Progression Marker Initiative (PPMI). We used linear mixed-effects models and reliable change indices (RCIs) to examine longitudinal associations between dysautonomia and dopamine transporter (DAT) striatal binding ratios (SBRs) measured by single-photon emission computerized tomography in PPMI participants over four years (n = 397 at baseline). Results: Adjusted mixed-models of longitudinal data showed that constipation—but not orthostatic hypotension or urinary dysfunction—was associated with reduced SBR in both caudate (P < 0.001) and putamen (P = 0.040). In both regions, SBR reductions between baseline and 4-year follow-up were significant and measurable (P < 0.0001), with larger decline and variance in the caudate nucleus. Four-year change in caudate—but not putaminal—SBR was significantly associated with RCI-indicated progression of GI dysautonomia (P = 0.031), but not other types of dysautonomia. These associations remained after adjusting for the use of medications or supplements to control constipation. Consistent with prior PPMI reports, motor impairment progression was not associated with SBR reduction. Conclusions: GI dysautonomia correlates with reductions in DAT availability; constipation is most closely associated with caudate-DAT reduction. Worsening GI-dysautonomia and reduced bowel movements may accompany advancing nigral degeneration or changes in nigrostriatal dopamine function.

KW - Autonomic

KW - Constipation

KW - Dopamine transporter

KW - Parkinson disease

KW - PPMI

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U2 - 10.1016/j.parkreldis.2018.08.010

DO - 10.1016/j.parkreldis.2018.08.010

M3 - Article

C2 - 30146185

AN - SCOPUS:85054349738

JO - Parkinsonism and Related Disorders

JF - Parkinsonism and Related Disorders

SN - 1353-8020

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