Three blood markers may help detect cognitive decline in Parkinson’s
Study: Biomarkers could help with early screening, disease monitoring
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- Three blood markers — CLU, NfL, and LDL-C — may help identify cognitive decline and assess its progression in Parkinson’s disease.
- Elevated CLU and NfL levels, combined with decreased LDL-C, effectively signal worsening cognitive and motor impairment.
- Further validation in larger studies is needed before these blood biomarkers are widely adopted in clinical practice.
Blood levels of three biomarkers — clusterin (CLU), neurofilament light chain (NfL), and low-density lipoprotein cholesterol (LDL-C) — may help identify cognitive impairment and assess its progression in people with Parkinson’s disease, a study suggests.
A model combining the three blood markers with measures of motor disease severity was highly accurate at distinguishing people with Parkinson’s who had normal cognition from those with mild cognitive impairment or dementia, as well as patients with mild cognitive impairment from those with dementia.
“The findings of this study hold significant clinical translational potential,” researchers wrote, noting that these blood biomarkers may help with “early screening, disease monitoring, and intervention assessment of cognitive impairment in [Parkinson’s disease].”
The study, “Serum clusterin, neurofilament light chain, and LDL-C cholesterol for risk stratification of cognitive impairment in parkinson’s disease,” was published in BMC Neurology.
Mild cognitive impairment can progress to Parkinson’s dementia
Parkinson’s is caused by the progressive loss of nerve cells that produce dopamine, a signaling molecule involved in motor control. This leads to motor symptoms, such as tremors, slow movements, and rigidity, and nonmotor symptoms including cognitive impairment.
Mild cognitive impairment is an early stage of cognitive decline that can progress to Parkinson’s disease dementia, when cognitive decline is severe enough to interfere with daily living. This highlights the importance of identifying patients at risk of cognitive impairment.
Blood biomarkers could provide a simple and accessible way to identify patients at risk of cognitive impairment.
In this study, researchers in China assessed whether the blood biomarkers CLU, NfL, and LDL-C could help detect cognitive decline earlier and monitor its progression.
According to researchers, the three biomarkers “may effectively capture distinct but interdependent facets of the disease process.”
NfL reflects nerve damage, CLU may represent a protective response to the buildup of abnormal proteins, and LDL-C may provide information about changes in fat metabolism that could be related to cognitive decline.
Blood biomarkers independently associated with cognitive impairment
The study enrolled 90 people with Parkinson’s who had been diagnosed at a hospital in China between January 2025 and February 2026, as well as 90 healthy controls. Participants with Parkinson’s had a mean age of 66.3 years and more than half were men (52.2%).
Compared with healthy controls, Parkinson’s patients had significantly higher blood levels of both CLU (1,176.9 vs. 828.4 picomoles per liter) and NfL (99.1 vs. 71.6 nanomoles per liter), and lower levels of LDL-C (2.4 vs. 3.2 millimoles per liter).
A total of 35 participants were classified as having normal cognition, 31 as having mild cognitive impairment, and 24 as having dementia, based on their Montreal Cognitive Assessment (MoCA) scores and clinical assessments. MoCA scores of 26 or higher indicated normal cognition, while those ranging between 18 to 25 indicated mild cognitive impairment, and those below 18 indicated dementia.
As cognitive impairment progressed from normal cognition to dementia, motor function also declined, as reflected by increasing Hoehn-Yahr and Unified Parkinson’s Disease Rating Scale Part 3 scores. At the same time, CLU and NfL levels progressively increased, while LDL-C levels decreased.
Further analysis showed that these clinical measures and biomarkers were all independently associated with cognitive impairment.
With further in-depth research and validation, this multi-indicator stratification model holds promise for broader application in clinical practice.
A model including these five factors was able to accurately at distinguish people with Parkinson’s disease and normal cognition from those with cognitive decline, with an area under the curve (AUC) of about 0.9.
AUC measures how well a test or model can distinguish between two groups, with an AUC of 1.0 representing perfect discrimination. Thus, an AUC of about 0.9 suggests the model had a very good ability to distinguish patients with and without cognitive impairment. A model including the three blood markers alone had an AUC of 0.896.
When distinguishing patients with mild cognitive impairment from those with dementia, the combined model had an AUC of 0.972, while the model using only the blood biomarkers had an AUC of 0.933.
Among individual blood markers, CLU was the one that performed best for distinguishing normal cognition from cognitive impairment, and mild cognitive impairment from dementia.
The researchers believe this approach could help doctors identify people with Parkinson’s who are at greater risk of cognitive decline, particularly those with mild cognitive impairment who are at higher risk of progressing to dementia.
However, they emphasized that the findings need to be confirmed in larger, prospective studies that follow patients over time.
“With further in-depth research and validation, this multi-indicator stratification model holds promise for broader application in clinical practice,” the researchers wrote.
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