Blood marker may help detect cognitive decline in Parkinson’s: Study
Specific ceramide ratio and inflammation combine to signal risk
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- A specific blood ceramide ratio is linked to worsening cognitive decline in Parkinson's disease.
- Higher levels of this ratio predict poorer cognitive performance, partially mediated by inflammation.
- This blood marker could help identify Parkinson's patients at risk for thinking and memory problems.
Higher blood levels of a specific ratio between two fats, called ceramides, may help identify people with Parkinson’s disease who are more likely to develop thinking and memory problems, according to a new study.
A higher Cer 24:1/Cer 24:0 ratio was closely associated with worsening cognitive impairment and remained a strong independent predictor of poorer cognitive performance after accounting for other factors. Inflammation appeared to partially mediate this association, highlighting ceramide metabolism and inflammatory signaling as complementary biological features of cognitive impairment in Parkinson’s disease.
“These findings establish a ceramide-centered quantitative framework integrating metabolic and inflammatory dimensions of cognitive impairment in [Parkinson’s], supporting stratified biomarker development,” researchers wrote.
The study, “Plasma ceramide ratios define metabolic–inflammatory associations with cognitive impairment in Parkinson’s disease,” was published in npj Parkinson’s Disease.
Cognitive changes often detected after damage has occurred in brain
A progressive neurological disorder, Parkinson’s is most known for causing motor symptoms, but it can also affect thinking and memory. Cognitive impairment can range from mild difficulties with attention, planning, and language to dementia, which develops in up to 80% of people with Parkinson’s over the course of the disease.
These cognitive changes are often detected only after significant damage has already occurred in the brain, limiting opportunities for early intervention. This “diagnostic lag,” together with the wide variation in the progression of cognitive impairment from person to person, highlights the need for accessible biomarkers that reflect the biological processes underlying cognitive decline, according to researchers.
One group of promising candidates is ceramides, a family of fatty molecules that help maintain nerve cell membranes, regulate communication between nerve cells, and modulate inflammation. Previous studies have linked abnormal ceramide metabolism to Parkinson’s and faster cognitive decline.
However, the specific ceramide profiles associated with different stages of cognitive impairment remain unclear, as do their relationships with inflammation and biomarkers of neurodegeneration.
To address this gap, researchers in China analyzed blood samples from 408 people with Parkinson’s, 98 people with multiple system atrophy (MSA), a neurological disorder that shares many symptoms with Parkinson’s, and 220 healthy adults.
Parkinson’s, MSA patients showed higher levels of several ceramides
Cognitive performance, as measured by the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination, was similar between people with Parkinson’s and MSA. However, the two groups differed in age, disease duration, disease and motor symptoms severity, and Parkinson’s medication use.
The researchers first measured levels of ceramides, inflammatory proteins called cytokines, and markers of nerve cell damage, including neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP).
Compared with healthy participants, both Parkinson’s and MSA participants showed higher levels of several ceramides and ceramide ratios, along with increased levels of most inflammatory cytokines, GFAP, and NfL.
Although Parkinson’s and MSA participants showed similar profiles of cytokines, GFAP, and NfL, people with MSA had significantly higher blood ratios of Cer 18:0/Cer 24:0 and Cer 24:1/Cer 24:0 than those with Parkinson’s. According to the researchers, these ceramide ratios may help distinguish between the two disorders, particularly in early stages where symptoms may overlap.
They then compared the findings with participants’ cognitive performance. Among people with Parkinson’s disease, worsening cognitive impairment was accompanied by progressively higher blood levels of several ceramides and ceramide ratios, inflammatory cytokines, GFAP, and NfL.
These changes were observed across the spectrum from normal cognition to mild cognitive impairment and Parkinson’s-related dementia, “indicating that metabolic, inflammatory, and neurodegenerative processes co-escalate at the stage of severe cognitive decline,” the researchers wrote.
Ratio an independent predictor of poor cognitive performance
Among the ceramide measures, the ratio of Cer 24:1 to Cer 24:0 showed the strongest association with cognitive performance, with higher blood levels associated with lower MoCA scores. Further statistical analyses showed the ratio remained an independent predictor of poor cognitive performance even after accounting for age, disease severity, and other factors that could influence cognition.
To better understand how ceramides, inflammation, and cognitive function might be related, the researchers used a statistical modeling approach. The model suggested that most of the association between ceramides-related measures and MoCA scores was direct, accounting for 60.8% of the overall effect, while about 36.2% appeared mediated by inflammation.
By contrast, pathways involving NfL did not significantly mediate this relationship, suggesting that inflammation may play a bigger role than nerve cell damage in the link between ceramides and cognitive impairment.
“Together, the model explained 37.1% of the variance in MoCA score and … supports further evaluation of ceramide metabolism and inflammatory signaling as complementary dimensions of cognitive impairment in [Parkinson’s],” the researchers wrote, while cautioning that future studies will be critical to validate the proposed ceramide-centered model.
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