Dataset Information

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.

SUBMITTER: Hinkle JT

PROVIDER: S-EPMC6291234 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

Dopamine transporter availability reflects gastrointestinal dysautonomia in early Parkinson disease.

Hinkle Jared T JT Perepezko Kate K Mills Kelly A KA Mari Zoltan Z Butala Ankur A Dawson Ted M TM Pantelyat Alexander A Rosenthal Liana S LS Pontone Gregory M GM

Parkinsonism & related disorders 20180822

<h4>Background</h4>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.<h4>Methods</h4>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-effect ...[more]

PMID: 30146185

Similar Datasets

Project description:ImportanceDetecting individuals at risk for Parkinson disease (PD) during the prodromal phase could clarify disease mechanisms and allow for treatment earlier in the disease process to possibly slow or prevent the onset of motor PD.ObjectiveTo determine if the combination of smell identification testing followed by dopamine transporter (DAT) imaging can accurately and efficiently identify individuals from the general population at risk for conversion to a clinical diagnosis of PD.Design, setting, and participantsParticipants were identified from the community by olfactory testing assessed longitudinally with DAT imaging 2 and 4 years after baseline and by annual clinical follow-up to determine whether they had clinical evidence to establish a PD diagnosis. Participants were contacted by mail and completed olfactory testing at home. Longitudinal follow-up of clinical measures and DAT imaging occurred at specialty centers. There were 203 hyposmic and 100 normosmic participants. A total of 185 hyposmic and 95 normosmic individuals had at least 1 follow-up visit, and 152 hyposmic participants (82.2%) were either observed for 4 years or converted to PD during follow-up.Main outcomes and measuresPercentage of individuals with hyposmia and a DAT deficit that converted to PD and the change in PD clinical scale scores (Unified Parkinson's Disease Rating Scale) and DAT imaging during 4-year follow-up.ResultsOf 280 total participants, 140 (50.0%) were male, and the mean (SD) age of the cohort was 63 (8.7) years. Among 21 participants with hyposmia and a DAT deficit (65% or less of age-expected lowest putamen binding ratio) at baseline, 14 (67%) converted to PD at 4 years compared with 2 of 22 participants (9%) with a DAT in an indeterminate range (greater than 65%-80%) and 3 of 109 participants (2.8%) with no DAT deficit (greater than 80%) at baseline. Individuals with a baseline DAT deficit experienced a 4-year decline in DAT binding of 20.23% (SD, 15.04%) compared with 3.68% (SD, 18.36%) and 5.45% (SD, 13.58%) for participants with an indeterminate and no DAT deficit, respectively (P = .002). The relative risk of conversion to a diagnosis of PD in hyposmic individuals with a DAT deficit was 17.47 (95% CI, 7.02-43.45) compared with individuals with either indeterminate or no DAT deficit.Conclusions and relevanceThe combination of hyposmia and DAT deficit was highly predictive of conversion to PD within 4 years of clinical follow-up. Individuals with hyposmia and a DAT deficit had a 5% reduction in DAT binding annually, similar to early PD. These results provide a framework for planning disease prevention studies in PD.

Dataset Information

Dopamine transporter availability reflects gastrointestinal dysautonomia in early Parkinson disease.

Background

Methods

Results

Conclusions

Publications

Dopamine transporter availability reflects gastrointestinal dysautonomia in early Parkinson disease.

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