Cerebrospinal fluid biomarkers of central dopamine deficiency predict Parkinson's disease.
Parkinsonism Relat Disord
; 50: 108-112, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29475591
ABSTRACT
BACKGROUND:
Consistent with nigrostriatal dopamine depletion, low cerebrospinal fluid (CSF) concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), the main neuronal metabolite of dopamine, characterize Parkinson's disease (PD) even in recently diagnosed patients. Whether low CSF levels of DOPAC or DOPA, the precursor of dopamine, identify pre-clinical PD in at-risk healthy individuals has been unknown.METHODS:
Participants in the intramural NINDS PDRisk study entered information about family history of PD, olfactory dysfunction, dream enactment behavior, and orthostatic hypotension at a protocol-specific website. After at least 3 risk factors were confirmed by on-site screening, 26 subjects had CSF sampled for levels of catechols and were followed for at least 3 years.RESULTS:
Of 26 PDRisk subjects, 4 were diagnosed with PD (Pre-Clinical PD group); 22 risk-matched (mean 3.2 risk factors) subjects remained disease-free after a median of 3.7 years (No-PD group). The Pre-Clinical PD group had lower initial DOPA and DOPAC levels than did the No-PD group (pâ¯=â¯0.0302, pâ¯=â¯0.0190). All 3 subjects with both low DOPA (<2.63â¯pmol/mL) and low DOPAC (<1.22â¯pmol/mL) levels, based on optimum cut-off points using the minimum distance method, developed PD, whereas none of 14 subjects with both normal DOPA and DOPAC levels did so (75% sensitivity at 100% specificity, pâ¯=â¯0.0015 by 2-tailed Fisher's exact test).CONCLUSIONS:
In people with multiple PD risk factors, those with low CSF DOPA and low CSF DOPAC levels develop clinical disease during follow-up. We suggest that neurochemical biomarkers of central dopamine deficiency identify the disease in a pre-clinical phase.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Ácido 3,4-Di-Hidroxifenilacético
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Dopamina
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Progressão da Doença
/
Sintomas Prodrômicos
Tipo de estudo:
Guideline
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Parkinsonism Relat Disord
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2018
Tipo de documento:
Article