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01-04-2016 | Neurology and Preclinical Neurological Studies - Original Article

Serum uric acid is associated with apathy in early, drug-naïve Parkinson’s disease

Published in: Journal of Neural Transmission | Issue 4/2016

Abstract

Both low serum uric acid (UA) levels and apathy are considered biomarkers of cognitive decline and dementia in Parkinson’s disease (PD). There is an urgent need to combine different biomarkers to predict disease course in PD. Data on the relationship between serum UA levels and apathy in PD are lacking. The aim of this study is to evaluate the relationship between serum UA levels and pure apathy in early, drug-naïve PD patients. Forty-nine early, drug-naïve PD patients were enrolled and stratified into two groups using the median serum UA levels at diagnosis (Group 1 serum UA ≤ 4.8 mg/dl; Group 2 serum UA > 4.8 mg/dl). The cohort was followed for the first 2 years of disease. Apathy was evaluated with the Apathy Evaluation Scale (AES). Patients with lower serum UA levels presented significant higher AES score compared to patients with higher serum UA levels. Regression analysis showed that baseline serum UA levels were significant determinants of AES scores at both baseline and 2-year follow up, irrespective of gender, age, attention/executive functions and dopamine replacement therapy when applicable. This is the first study showing a link between serum UA levels and apathy in non-demented, non-depressed, early, drug-naïve PD, being lower serum UA levels associated with greater apathy. Further follow up of our patients and replication of this observation in independent cohorts are needed to establish if this combination of biomarkers may help in characterizing a subgroup of PD patients at diagnosis.

American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edition, text revised, DSM-IV-TR. American Psychiatric Association, Washington

Annanmaki T, Pessala-Driver A, Hokkanen L, Murros K (2008) Uric acid associates with cognition in Parkinson’s disease. Parkinsonism Relat Disord 14(7):576–578CrossRefPubMed

Annanmaki T, Pohja M, Parviainen T, Hakkinen P, Murros K (2011) Uric acid and cognition in Parkinson’s disease: a follow-up study. Parkinsonism Relat Disord 17(5):333–337CrossRefPubMed

Anumonye A, Dobson JW, Oppenheim S, Sutherland JS (1969) Plasma uric acid concentrations among Edinburgh business executives. JAMA 208(7):1141–1144CrossRefPubMed

Barbarotto R, Laiacona M, Frosio R, Vecchio M, Farinato A, Capitani E (1998) A normative study on visual reaction times and two Stroop colour word tests. Ital J Neurol Sci 19:161–170CrossRefPubMed

Bos MJ, Koudstaal PJ, Hofman A, Witteman JC, Breteler MM (2006) Uric acid is a risk factor for myocardial infarction and stroke; The Rotterdam Study. Stroke 37:1503–1507CrossRefPubMed

Brooks GW, Mueller E (1966) Serum urate concentrations among university professors; relation to drive, achievement, and leadership. JAMA 195(6):415–418CrossRefPubMed

Carlesimo GA, Caltagirone C, Gainotti G (1996) The mental deterioration battery: normative data, diagnostic reliability and qualitative analyses of cognitive impairment. The Group for the Standardization of the mental deterioration battery. Eur Neurol 36:378–384CrossRefPubMed

Chen X, Wu G, Schwarzschild MA (2012) Urate in parkinson’s disease: more than a biomarker? Curr Neurol Neurosci Rep 12:367–375CrossRefPubMed

de Lau LM, Koudstaal PJ, Hofman A, Breteler MM (2005) Serum uric acid levels and the risk of Parkinson disease. Ann Neurol 58(5):797–800CrossRefPubMed

Dujardin K, Sockeel P, Delliaux M, Destée A, Defebvre L (2009) Apathy may herald cognitive decline and dementia in Parkinson’s disease. Mov Disord 24:2391–2397CrossRefPubMed

Emre M, Aarsland D, Brown R et al (2007) Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord 22:1689–1707CrossRefPubMed

Euser SM, Hofman A, Westendorp RG, Breteler MM (2009) Serum uric acid and cognitive function and dementia. Brain 132(Pt 2):377–382PubMed

Fahn S, Elton RL, UPDRS program members (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Mardsen CD, Goldstein M, Calne DB (eds) Recent developments in Parkinson’s disease, vol 2. Florham Park N, Macmillan Healthcare Information, pp 153–163

Fang J, Alderman MH (2000) Serum uric acid and cardiovascular mortality; The NHANES I epidemiologic follow-up study, 1971–1992. JAMA 283:2404–2410CrossRefPubMed

Folstein MF, Folstein SE, MCHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198CrossRefPubMed

Fowler MG (1973) Relationship of serum uric acid to achievement motivation. Psychosom Med 35(1):13–22CrossRefPubMed

Gilman S, Wenning GK, Low PA et al (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71:670–676CrossRefPubMedPubMedCentral

Giovagnoli AR, Del Pesce M, Mascheroni S, Simoncelli M, Laiacona M, Capitani E (1996) Trail making test: normative values from 287 normal adult controls. Ital J Neurol Sci 17:305–309CrossRefPubMed

Grossi D, Santangelo G, Barbarulo AM et al (2013) Apathy and related executive syndromes in dementia associated with Parkinson’s disease and in Alzheimer’s disease. Behav Neurol 27(4):515–522CrossRefPubMed

Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442CrossRefPubMed

Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinic-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184CrossRefPubMedPubMedCentral

Kasl SV, Brooks GW, Cobb S (1966) Serum urate concentrations in male high-school students. JAMA 198(7):713–716CrossRefPubMed

Kasl SV, Brooks GW, Rodgers WL (1970) Serum uric acid and cholesterol in achievement behavior and motivation. II. The relationship to college attendance, extracurricular and social activities, and vocational aspirations. JAMA 213(8):1291–1299CrossRefPubMed

Kirsch-Darrow L, Fernandez HH, Marsiske M, Okun MS, Bowers D (2006) Dissociating apathy and depression in Parkinson disease. Neurology 67:33–38CrossRefPubMedPubMedCentral

Kirsch-Darrow L, Marsiske M, Okun MS, Bauer R, Bowers D (2011) Apathy and depression: separate factors in Parkinson’s disease. J Int Neuropsychol Soc: JINS 17(6):1058–1066CrossRefPubMedPubMedCentral

Lang AE, Riley DE, Bergeron C (1994) Cortical-basal ganglionic degeneration. In: Calne DB (ed) Neurodegenerative diseases. WB Saunders, Philadelphia, pp 877–894

Litvan I, Agid Y, Calne D et al (1996) Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 47:1–9CrossRefPubMed

Lorenzi TM, Borba DL, Dutra G, Lara DR (2010) Association of serum uric acid levels with emotional and affective temperaments. J Affect Disord 121(1–2):161–164CrossRefPubMed

Marin RS (1991) Apathy: a neuropsychiatric syndrome. J Neuropsychiatry Clin Neurosci 3(3):243–254CrossRefPubMed

Marin RS, Biedrzycki RC, Firinciogullari S (1991) Reliability and validity of the apathy evaluation scale. Psychiatry Res 38(2):143–162CrossRefPubMed

McKeith IG, Galasko D, Kosaka K et al (1996) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 47:1113–1124CrossRefPubMed

McKeown MJ, Peavy GM (2015) Biomarkers in Parkinson disease: it’s time to combine. Neurology 84(24):2392–2393CrossRefPubMed

Miller NJ, Rice-Evans C, Davies MJ, Gopinathan V, Milner A (1993) A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci 84:407–412CrossRefPubMed

Moccia M, Picillo M, Erro R, Vitale C et al (2014) Is serum uric acid related to non-motor symptoms in de-novo Parkinson’s disease patients? Parkinsonism Relat Disord 20(7):772–775CrossRefPubMed

Moccia M, Picillo M, Erro R et al (2015a) Presence and progression of non-motor symptoms in relation to uric acid in de novo Parkinson’s disease. Eur J Neurol 22(1):93–98CrossRefPubMed

Moccia M, Pappatà S, Erro R et al (2015b) Uric acid relates to dopamine transporter availability in Parkinson’s disease. Acta Neurol Scand 131(2):127–131CrossRefPubMed

Mondolo F, Jahanshahi M, Granà A, Biasutti E, Cacciatori E, Di Benedetto P (2006) The validity of the hospital anxiety and depression scale and the geriatric depression scale in Parkinson’s disease. Behavioral Neurology 17(2):109CrossRefPubMed

Mueller EF, Kasl SV, Brooks GW, Cobb S (1970) Psychosocial correlates of serum urate levels. Psychol Bull 73(4):238–257CrossRefPubMed

Picillo M, Erro R, Santangelo G et al (2013) Insulin-like growth factor-1 and progression of motor symptoms in early, drug-naïve Parkinson’s disease. J Neurol 260(7):1724–1730CrossRefPubMed

Rahe RH, Rubin RT, Gunderson EK (1972) Measures of subjects motivation and affect correlated with their serum uric acid, cholesterol, and cortisol. Arch Gen Psychiatry 26(4):357–359CrossRefPubMed

Robert PH, Onyike CU, Leentjens AFG et al (2009) Proposed diagnostic criteria for apathy in Alzheimer’s disease and other neuropsychiatric disorders. Eur Psychiatry 24:98–104CrossRefPubMed

Santangelo G, Trojano L, Barone P, Errico D, Grossi D, Vitale C (2013) Apathy in Parkinson’s disease: diagnosis, neuropsychological correlates, pathophysiology and treatment. Behav Neurol 27(4):501–513CrossRefPubMed

Santangelo G, Barone P, Cuoco S et al (2014) Apathy in untreated, de novo patients with Parkinson’s disease: validation study of Apathy evaluation scale. J Neurol 261(12):2319–2328CrossRefPubMed

Santangelo G, Vitale C, Trojano L, Picillo M, Moccia M, Pisano G et al (2015a) Relationship between apathy and cognitive dysfunctions in de novo untreated Parkinson’s disease: a prospective longitudinal study. Eur J Neurol 22(2):253–260CrossRefPubMed

Santangelo G, Vitale C, Picillo M et al (2015b) Apathy and striatal dopamine transporter levels in de-novo, untreated Parkinson’s disease patients. Parkinsonism Relat Disord 21(5):489–493CrossRefPubMed

Sutin AR, Cutler RG, Camandola S et al (2014) Impulsivity is associated with uric acid: evidence from humans and mice. Biol Psychiatry 75(1):31–37CrossRefPubMed

Thobois S, Lhommée E, Klinger H et al (2013) Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptor with piribedil. Brain 136:1568–1577CrossRefPubMed

Varanese S, Perfetti B, Ghilardi MF, Di Rocco A (2011) Apathy, but not depression, reflects inefficient cognitive strategies in Parkinson’s disease. PLoS One 6(3):e17846CrossRefPubMedPubMedCentral

Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67(6):361–370CrossRefPubMed

Ziropadja L, Stefanova E, Petrovic M, Stojkovic T, Kostic VS (2012) Apathy and depression in Parkinson’s disease: the Belgrade PD study report. Parkinsonism Relat Disord 18(4):339–342CrossRefPubMed

Title: Serum uric acid is associated with apathy in early, drug-naïve Parkinson’s disease
Publication date: 01-04-2016
Published in: Journal of Neural Transmission / Issue 4/2016
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-015-1502-5

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Serum uric acid is associated with apathy in early, drug-naïve Parkinson’s disease

Abstract

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