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

Abstract

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.

Differential effects of sex on longitudinal patterns of cognitive decline in Parkinson’s disease

“…Three hundred and ninety-two home-based PwP (64.5% males, 35.5% females) were recruited sequentially into the Australian Parkinson’s Disease Registry (APDR) as previously described [ 8 , 21 ]. In brief, participants were enrolled from Movement Disorders Clinics at the Perron Institute for Neurological and Translational Science (Perth, Western Australia), St. Vincent’s Hospital (Melbourne, Victoria), and Royal North Shore Hospital (Sydney, New South Wales), between 2012 and 2019.…”

“…Each participant was evaluated by a trained cognition researcher and completed a panel of standardised neuropsychological assessments, as previously described [ 8 , 21 ]. In addition, cognitive function was assessed in this study using the revised ‘Addenbrooke’s Cognitive Examination’ (ACE-R).…”

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

“…Global cognition impairments were assessed using Addenbrooke's Cognitive Examination-Revised (ACE-R) [21], which has been used previously to determine cognitive impairment in PD patient cohorts [22, 23]. The ACE-R evaluated five prominent cognitive domains, with a maximum total score of 100 points: orientation and attention (18 points), memory (26 points), verbal fluency (14 points), language (26 points), and visuospatial (16 points) abilities.…”

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.…”