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      Elevated Serum Ceruloplasmin Levels Are Associated with Higher Impulsivity in People with Parkinson's Disease

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          Abstract

          Background

          Heightened impulsivity has been reported in a subset of people with Parkinson's disease (PwP) and is considered a risk factor for the development of impulse control disorders (ICDs). However, at present, there are no recognised biochemical markers of heightened impulsivity.

          Objectives

          To determine if ceruloplasmin, a serum marker involved in the regulation of iron and copper homeostasis, is associated with trait impulsivity in PwP.

          Methods

          The study measured serum ceruloplasmin and impulsivity using the Barratt Impulsiveness Scale (BIS-11) in an Australian cohort of 214 PwP. Multivariate general linear models (GLMs) were used to identify whether higher serum ceruloplasmin levels (>75th percentile) were significantly predictive of BIS-11 scores.

          Results

          Serum ceruloplasmin was higher in females with PD ( p < 0.001) and associated with MDS-UPDRS III, Hoehn and Yahr, and ACE-R scores ( p < 0.05). When correcting for covariates, higher serum ceruloplasmin concentrations were associated with the 2 nd order nonplanning impulsivity and with the 1st order self-control and cognitive complexity impulsivity domains.

          Conclusions

          Higher serum ceruloplasmin levels are independently associated with heightened nonplanning impulsivity in PwP. Thus, serum ceruloplasmin levels may have clinical utility as a marker for heightened impulsivity in PD.

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          Most cited references43

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          The Addenbrooke's Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening.

          Eneida Mioshi, Kate Dawson, Joanna Mitchell … (2006)
          There is a clear need for brief, but sensitive and specific, cognitive screening instruments as evidenced by the popularity of the Addenbrooke's Cognitive Examination (ACE). We aimed to validate an improved revision (the ACE-R) which incorporates five sub-domain scores (orientation/attention, memory, verbal fluency, language and visuo-spatial). Standard tests for evaluating dementia screening tests were applied. A total of 241 subjects participated in this study (Alzheimer's disease=67, frontotemporal dementia=55, dementia of Lewy Bodies=20; mild cognitive impairment-MCI=36; controls=63). Reliability of the ACE-R was very good (alpha coefficient=0.8). Correlation with the Clinical Dementia Scale was significant (r=-0.321, p<0.001). Two cut-offs were defined (88: sensitivity=0.94, specificity=0.89; 82: sensitivity=0.84, specificity=1.0). Likelihood ratios of dementia were generated for scores between 88 and 82: at a cut-off of 82 the likelihood of dementia is 100:1. A comparison of individual age and education matched groups of MCI, AD and controls placed the MCI group performance between controls and AD and revealed MCI patients to be impaired in areas other than memory (attention/orientation, verbal fluency and language). The ACE-R accomplishes standards of a valid dementia screening test, sensitive to early cognitive dysfunction. Copyright (c) 2006 John Wiley & Sons, Ltd.
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            Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls.

            Heywood M. Petry, Jason K Kirby, Warren Bickel (1999)
            Fifty-six heroin addicts and 60 age-matched controls were offered choices between monetary rewards ($11-$80) available immediately and larger rewards ($25-$85) available after delays ranging from 1 week to 6 months. Participants had a 1-in-6 chance of winning a reward that they chose on one randomly selected trial. Delay-discounting rates were estimated from the pattern of participants' choices. The discounting model of impulsiveness (Ainslie, 1975) implies that delay-discounting rates are positively correlated with impulsiveness. On average, heroin addicts' discount rates were twice those of controls (p = .004), and discount rates were positively correlated with impulsivity as measured by self-report questionnaires (p < .05). The results lend external validity to the delay-discounting rate as a measure of impulsiveness, a characteristic associated with substance abuse.
            Article 0 comments Cited 186 times – based on 0 reviews     Review now
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              The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis?

              Madelyn C Houser, Malú G. Tansey (2017)
              The state of the intestinal environment can have profound effects on the activity of the central nervous system through the physiological contributions of the microbiota, regulation of intestinal barrier function, and altered activity of peripheral neurons. The common language employed for much of the gut-brain communication is the modulation of immune activity. Chronic proinflammatory immune activity is increasingly being recognized as a fundamental element of neurodegenerative disorders, and in Parkinson’s disease, inflammation in the intestine appears particularly relevant in pathogenesis. We review the evidence that intestinal dysfunction is present in Parkinson’s disease and that it may reflect the earliest manifestations of Parkinson’s disease pathology, and we link these findings to dysregulated immune activity. Based on this, we present a model for Parkinson’s disease pathogenesis in which the disorder originates in the intestine and progresses with inflammation as its underlying mechanism. More in-depth investigations into the physiological mechanisms underlying peripheral pre-motor symptoms in Parkinson’s disease are expected to lead to the development of novel diagnostic and therapeutic measures that can slow or limit progression of the disease to more advanced stages involving debilitating motor and cognitive symptoms.
              Article 0 comments Cited 165 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Ryan S. Anderton:
                ORCID: https://orcid.org/0000-0003-0568-9794
                Journal
                Journal ID (nlm-ta): Parkinsons Dis
                Journal ID (iso-abbrev): Parkinsons Dis
                Journal ID (publisher-id): PD
                Title: Parkinson's Disease
                Publisher: Hindawi
                ISSN (Print): 2090-8083
                ISSN (Electronic): 2042-0080
                Publication date Collection: 2020
                Publication date (Electronic): 30 September 2020
                Volume: 2020
                Electronic Location Identifier: 8296203
                Affiliations
                1Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, Australia
                2Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Nedlands, Western Australia, Australia
                3School of Health Sciences, University of Notre Dame Australia, Fremantle, Western Australia, Australia
                4Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia
                5Centre for Clinical Neurosciences and Neurological Research, St. Vincent's Hospital Melbourne, Fitzroy, Victoria 3065, Australia
                6Institute for Health Research, University of Notre Dame Australia, Fremantle, Western Australia, Australia
                7Centre for Molecular Medicine & Innovative Therapeutics, Murdoch University, Perth, Western Australia, Australia
                Author notes

                Academic Editor: Carlo Ferrarese

                Author information
                https://orcid.org/0000-0003-0568-9794
                Article
                DOI: 10.1155/2020/8296203
                PMC ID: 7545407
                SO-VID: abaa1ab7-c7ad-4f38-9632-1e7e21cf3437
                Copyright © Copyright © 2020 Megan C. Bakeberg et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 28 May 2020
                Date revision received : 21 August 2020
                Date accepted : 19 September 2020
                Funding
                Funded by: Federal Cooperative Research Centre for Mental Health
                Funded by: Perron Institute for Neurological and Translational Science
                Funded by: University of Notre Dame Australia
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Neurology
                Data availability:
                ScienceOpen disciplines: Neurology

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