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

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 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.

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

“…While one recent study examined the association between lipid levels and PD-related symptoms, no significant associations were noted (Choe et al, 2021). However, an increasing body of literature indicates notable sex-differences among various aspects of the clinical presentation of PD (Augustine et al, 2015;Liu et al, 2015;Bakeberg et al, 2020a), and cognitive impairment specifically (Bakeberg et al, 2019(Bakeberg et al, , 2021. Thus, it is of utmost importance to examine these associations in light of such sex-differences.…”

The crosstalk between the “inflamed” mind and the “impulsive” mind: activation of microglia and impulse control disorders

“…These behaviors can be clinically assessed and quantified based on four dimensions of impulsivity: urgency, lack of premeditation, lack of perseverance, and sensation seeking [9]. As neurodegeneration progresses, patients could develop impulse-control disorders with several pathological hallmarks: lower a-synuclein load and D3 receptor in nucleus accumbens were found in PD patients with impulsive-compulsive behaviors [30]; the noradrenaline reuptake inhibitor, atomoxetine, could improve impulsivity in PD patients by compensating the noradrenergic loss of projections from the locus coeruleus [31]; higher serum ceruloplasmin, acute-phase plasma proteins that activate macrophages and other immune cells [32], was positively correlated with non-planning impulsivity in PD patients [33]. Although currently there is little direct evidence linking neuroinflammatory markers with impulsive behaviors in PD and AD, it is highly speculative that persistent neuroinflammation might impair neural substrates and neurocircuits related to impulse control.…”