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

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 2nd 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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Trait Impulsivity Is Independent of Mild Cognitive Impairment in a Parkinson’s Disease Cohort

Parkinson s Disease ◽

10.1155/2019/2672075 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Ashani Jeyadevan ◽

Megan C. Bakeberg ◽

Michelle Byrnes ◽

Jade Kenna ◽

Soumya Ghosh ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Complexity ◽

Self Control ◽

Cognitive State ◽

Normal Cognitive Function ◽

Trait Impulsivity ◽

Motor Impulsivity

Introduction. Patients with Parkinson’s disease (PD) commonly experience cognitive deficits and some also develop impulse control disorders (ICDs); however, the relationship between impulsivity and cognitive dysfunction remains unclear. This study investigated whether trait impulsivity associates with mild cognitive impairment (MCI), or is altered in a PD patient cohort with MCI. Methods. A total of 302 patients with idiopathic PD were recruited sequentially from three Australian Movement Disorder clinics. Based on cognitive scores, participants were divided into two groups, one defined as having mild cognitive impairment (PD-MCI; n = 113) and the other with normal cognitive function (PD-C; n = 189). Trait impulsivity was evaluated using the Barrett Impulsiveness Scale 11 (BIS-11). Total impulsivity scores, as well as subscale scores, were compared between PD-C and PD-MCI groups. Results. The PD-MCI cohort had significantly lower scores in all cognitive domains, and mirrored expected clinical differences in medication, motor symptoms, and disease duration, when compared to the PD-C cohort. Self-reported impulsivity was not significantly different between groups, nor was there a difference within first-order subscale scores: attention p=0.137, cognitive instability p=0.787, self-control p=0.503, cognitive complexity p=0.157, motor impulsivity p=0.559, or perseverance p=0.734 between the PD-MCI and PD-C groups. Conclusions. These findings suggest that impulsive traits and behaviors are independent of changes in cognitive state and are not altered in PD patients with mild cognitive impairment.

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Demographic and Clinical Predictors of Trait Impulsivity in Parkinson’s Disease Patients

Parkinson s Disease ◽

10.1155/2018/9472120 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Maddeson Riley ◽

Megan Bakeberg ◽

Michelle Byrnes ◽

Alexa Jefferson ◽

Soumya Ghosh ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Secondary Education ◽

Postsecondary Education ◽

Disease Severity ◽

Linear Models ◽

Male Gender ◽

Clinical Predictors ◽

Trait Impulsivity ◽

History Of

Background. Impulsive behaviour has become increasingly recognised as a neuropsychiatric complication of Parkinson’s disease (PD). Thought to be a product of compromised cognitive control, the spectrum of impulsive behaviours in PD ranges from cognitive disinhibition to impulse control disorders (ICDs). Objective. At present, there are no indicators for trait impulsivity in PD. The objective of the current study was to identify demographic and clinical predictors of susceptibility to trait impulsivity in a cohort of PD patients. Methods. The current study assessed impulsivity using the Barratt Impulsiveness Scale 11 (BIS-11) in a cohort of 87 PD patients. General linear models (GLMs) were used to identify clinical and demographic variables predictive of heightened BIS-11 second-order attentional and nonplanning subscale scores. Results. Male gender, no history of smoking, postsecondary education, and heightened disease severity were predictive of increased BIS-11 attentional scores (p<0.05). Similarly, male gender, after secondary education, and disease severity were predictive of increased BIS-11 nonplanning scores (p<0.05). Contrary to previous reports, dopaminergic medication use was not a significant determinant of either BIS-11 subscale scores. Conclusions. Several demographic and clinical variables including male gender, no history of past smoking, after secondary education, and elevated disease severity are associated with impulsivity in PD.

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Elevated Serum Homocysteine Levels Have Differential Gender-Specific Associations with Motor and Cognitive States in Parkinson’s Disease

Parkinson s Disease ◽

10.1155/2019/3124295 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Megan C. Bakeberg ◽

Alexa Jefferson ◽

Maddeson Riley ◽

Michelle Byrnes ◽

Soumya Ghosh ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Vitamin B12 ◽

Linear Models ◽

Elevated Serum ◽

Significant Negative Correlation ◽

Healthy Controls ◽

Serum Homocysteine ◽

Symptom Progression ◽

Gender Specific

Background. Studies attempting to elucidate an association between homocysteine and symptom progression in Parkinson’s disease (PD) have had largely discrepant findings. This study aimed to investigate elevated serum homocysteine levels and symptom progression in a cohort of PD patients. Methods. Serum homocysteine, folate, and vitamin B12 levels were measured in 205 people with PD and 78 age-matched healthy controls. People with Parkinson’s disease underwent a battery of clinical assessments to evaluate symptom severity, including motor (MDS-UPDRS) and cognitive (ACE-R) assessments. Multivariate generalised linear models were created, controlling for confounding variables, and were used to determine whether serum markers are associated with various symptom outcome measures. Results. People with Parkinson’s disease displayed significantly elevated homocysteine levels (p<0.001), but not folate or vitamin B12 levels, when compared to healthy controls. A significant positive correlation between homocysteine and MDS-UPDRS III score was identified in males with Parkinson’s disease (rs = 0.319, p<0.001), but not in females, whereas a significant negative correlation between homocysteine levels and total ACE-R score was observed in females with Parkinson’s disease (rs = −0.449, p<0.001), but not in males. Multivariate general linear models confirmed that homocysteine was significantly predictive of MDS-UPDRS III score in male patients (p=0.004) and predictive of total ACE-R score in female patients (p=0.021). Conclusion. Elevated serum homocysteine levels are associated with a greater motor impairment in males with Parkinson’s disease and poorer cognitive performance in females with Parkinson’s disease. Our gender-specific findings may help to explain previous discrepancies in the literature surrounding the utility of homocysteine as a biomarker in PD.

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The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease

Scientific Reports ◽

10.1038/s41598-021-85510-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Megan C. Bakeberg ◽

Madison E. Hoes ◽

Anastazja M. Gorecki ◽

Frances Theunissen ◽

Abigail L. Pfaff ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Symptom Onset ◽

Disease Risk ◽

Age Of Onset ◽

Sequencing Analysis ◽

Age Related ◽

Australian Cohort ◽

Progression Markers ◽

Age Related Cognitive Decline

AbstractAbnormal mitochondrial function is a key process in the pathogenesis of Parkinson’s disease (PD). The central pore-forming protein TOM40 of the mitochondria is encoded by the translocase of outer mitochondrial membrane 40 homologue gene (TOMM40). The highly variant ‘523’ poly-T repeat is associated with age-related cognitive decline and age of onset in Alzheimer’s disease, but whether it plays a role in modifying the risk or clinical course of PD it yet to be elucidated. The TOMM40 ‘523’ allele length was determined in 634 people with PD and 422 healthy controls from an Australian cohort and the Parkinson’s Progression Markers Initiative (PPMI) cohort, using polymerase chain reaction or whole genome sequencing analysis. Genotype and allele frequencies of TOMM40 ‘523’ and APOE ε did not differ significantly between the cohorts. Analyses revealed TOMM40 ‘523’ allele groups were not associated with disease risk, while considering APOE ε genotype. Regression analyses revealed the TOMM40 S/S genotype was associated with a significantly later age of symptom onset in the PPMI PD cohort, but not after correction for covariates, or in the Australian cohort. Whilst variation in the TOMM40 ‘523’ polymorphism was not associated with PD risk, the possibility that it may be a modifying factor for age of symptom onset warrants further investigation in other PD populations.

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Characterizing the spiking dynamics of subthalamic nucleus neurons in Parkinson's disease using generalized linear models

Frontiers in Integrative Neuroscience ◽

10.3389/fnint.2012.00028 ◽

2012 ◽

Vol 6 ◽

Cited By ~ 5

Author(s):

Uri T. Eden ◽

John T. Gale ◽

Ramin Amirnovin ◽

Emad N. Eskandar

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Subthalamic Nucleus ◽

Generalized Linear Models ◽

Linear Models

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Elevated HDL Levels Linked to Poorer Cognitive Ability in Females With Parkinson’s Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.656623 ◽

2021 ◽

Vol 13 ◽

Author(s):

Megan C. Bakeberg ◽

Anastazja M. Gorecki ◽

Jade E. Kenna ◽

Alexa Jefferson ◽

Michelle Byrnes ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Function ◽

Cognitive Performance ◽

Linear Models ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Cognitive Status ◽

Cross Sectional ◽

Age Related

IntroductionCholesterol levels have been associated with age-related cognitive decline, however, such an association has not been comprehensively explored in people with Parkinson’s disease (PD). To address this uncertainty, the current cross-sectional study examined the cholesterol profile and cognitive performance in a cohort of PD patients.MethodsCognitive function was evaluated using two validated assessments (ACE-R and SCOPA-COG) in 182 people with PD from the Australian Parkinson’s Disease Registry. Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and Triglyceride (TRG) levels were examined within this cohort. The influence of individual lipid subfractions on domain-specific cognitive performance was investigated using covariate-adjusted generalised linear models.ResultsFemales with PD exhibited significantly higher lipid subfraction levels (TC, HDL, and LDL) when compared to male counterparts. While accounting for covariates, HDL levels were strongly associated with poorer performance across multiple cognitive domains in females but not males. Conversely, TC and LDL levels were not associated with cognitive status in people with PD.ConclusionHigher serum HDL associates with poorer cognitive function in females with PD and presents a sex-specific biomarker for cognitive impairment in PD.

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Cognitive Influences in Parkinson's Disease Patients and Their Caregivers: Perspectives From an Australian Cohort

Frontiers in Neurology ◽

10.3389/fneur.2021.673816 ◽

2021 ◽

Vol 12 ◽

Author(s):

Michal Lubomski ◽

Ryan L. Davis ◽

Carolyn M. Sue

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Cognitive Influences ◽

Lower Education Level ◽

Caregiver Quality ◽

Australian Cohort ◽

Lower Education ◽

Non Motor Symptoms

Objectives: Cognitive impairment impacts negatively on Parkinson's disease (PD) patient and caregiver quality of life (QoL). We examined cognitive impairment in PD patients and their caregivers to determine if caregiver cognition affected their PD relative.Methods: Validated cognition and clinical outcome measures were assessed in 103 PD patients and 81 caregivers.Results: PD patients showed more cognitive impairment than their carers, with 48.6% having possible Mild Cognitive Impairment (MCI) and 16.5% having PD dementia. Increasing age, male gender, lower education level, various non-motor symptoms and certain therapies, associated with poorer cognition in PD. Eighteen and a half percent of caregivers were found to have MCI, in association with a lower physical and mental QoL. This reflected in lower QoL and mood for the respective PD patients.Conclusion: Impaired cognition and QoL in caregivers was associated with decreased QoL and mood for respective PD patients, suggesting MCI in caregivers is an important consideration for the management of PD.

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