Study Identifies Biomarkers for Motor, Cognitive Decline in Early Parkinson’s

Urate, a salt derived from uric acid, and homocysteine, an amino acid, may predict motor and cognitive decline in early Parkinson’s disease, researchers report.

The study with that finding, “Urate and Homocysteine: Predicting Motor and Cognitive Changes in Newly Diagnosed Parkinson’s Disease” was published in the Journal of Parkinson’s Disease.

Low levels of urate have been associated with a higher risk of developing Parkinson’s over the subsequent 15 to 20 years. Low urate plasma concentrations also have been linked to cognitive decline, including poorer performance in attention, executive, and visuospatial functions.

High levels of homocysteine — an amino acid produced by the body, usually as a byproduct of consuming meat — also has been reported to increase the risk of dementia in older adults, suggesting it may play a role in the development of Parkinson’s disease dementia (PDD).

Researchers at Newcastle University, London, England, examined the association between urate and homocysteine levels, disease progression and cognitive status over 4.5 years in early Parkinson’s disease.

A total of 154 recently diagnosed Parkinson’s patients (100 men and 54 women, mean age 66.4 years) and 99 age-matched control subjects (54 men and forty-five women, mean age 67.9 years) underwent medical assessment by a movement disorders specialist. Participants with Parkinson’s disease were evaluated in the “on” motor state (when medication is taking effect and has not worn off) and patients were able to move smoothly.

Data on disease duration, concurrent diseases, medications, smoking history, and alcohol consumption were collected.

Motor symptoms’ severity was quantified using the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III and the Hoehn and Yahr scale. Cognition was assessed using the Montreal Cognitive Assessment (MoCa).

Blood samples were drawn only at the study participants’ initial visit and screened for urate, homocysteine, red cell folate (to measure the body’s store of folic acid) and vitamin B12 (an essential nutrient mainly present in meat and fish). Participants were examined  four times: at the study’s initial visit (baseline) and then at 18, 36 and 54 months.

At the first visit, 73% of Parkinson’s patients were levodopa (L-DOPA) naïve, meaning they were not yet taking prescribed anti-parkinsonian medications. No significant differences were found between treated and levodopa naïve patients regarding serum urate and serum homocysteine levels.

Participants with Parkinson’s disease had significantly lower baseline urate concentrations (302.7 μmol/L) than healthy controls (331.4 μmol/L). This also was true after 18 and 36 months.

On the contrary, plasma homocysteine levels were significantly higher than those observed in healthy controls, both at baseline (11.1 vs. 9.6 μmol/L) and at 18 and 36 months.

Lower urate concentration and higher homocysteine levels were associated with worsening of motor function in early diagnosed Parkinson’s patients. However, only higher homocysteine levels at baseline correlated with worse cognitive scores over 4.5 years of follow-up.

The findings suggest both urate and homocysteine can be biomarkers that help predict motor function decline, while only homocysteine predicts cognitive changes in early Parkinson’s disease.

“These findings lend support to the hypothesis that oxidative stress may play a role in the pathophysiology of PD [Parkinson’s disease] and that motor and cognitive aspects of the disease may have overlapping but separate mechanisms,” researchers wrote.

Of note, oxidative stress is an imbalance between the production of free radicals and the ability of cells to detoxify them, resulting in cellular damage as a consequence of high levels of oxidant molecules.

“In addition to potential disease modification, our findings suggest that determining urate and homocysteine concentration at the outset may have a role in predicting patients with PD [Parkinson’s disease] at greater risk of decline in motor and cognitive function,” they concluded.