Three blood biomarkers may help identify cognitive decline and track its progression in people with Parkinson’s disease, a study suggests.
Researchers found that clusterin (CLU), neurofilament light chain (NfL) and low-density lipoprotein cholesterol (LDL-C) were independently associated with cognitive impairment.
Combining the three markers with measures of motor disease severity allowed researchers to distinguish patients with normal cognition from those with mild cognitive impairment or dementia.
Researchers in China assessed the biomarkers in 90 people with Parkinson’s diagnosed at a hospital between January 2025 and February 2026, alongside 90 healthy controls.
Participants with Parkinson’s had a mean age of 66.3 years and 52.2 per cent were men.
Compared with healthy controls, people with Parkinson’s had significantly higher levels of CLU and NfL and lower levels of LDL-C.
NfL reflects nerve damage. Researchers said CLU may reflect a protective response to abnormal protein accumulation, while LDL-C may provide information about changes in fat metabolism potentially related to cognitive decline.
Among the Parkinson’s group, 35 participants had normal cognition, 31 had mild cognitive impairment and 24 had dementia, based on Montreal Cognitive Assessment scores and clinical assessments.
Mild cognitive impairment is an early stage of cognitive decline that can progress to Parkinson’s disease dementia, when cognitive difficulties become severe enough to interfere with daily living.
As cognitive impairment progressed from normal cognition to dementia, CLU and NfL levels increased while LDL-C levels decreased.
Motor function also declined, reflected by increasing Hoehn-Yahr and Unified Parkinson’s Disease Rating Scale Part 3 scores.
Further analysis found that the clinical measures and blood biomarkers were independently associated with cognitive impairment.
A model combining the three biomarkers with two measures of motor disease severity achieved an area under the curve, or AUC, of about 0.9 when distinguishing people with normal cognition from those with cognitive decline.
AUC measures how well a test distinguishes between two groups, with 1.0 representing perfect discrimination.
Using the three blood markers alone produced an AUC of 0.896.
When distinguishing mild cognitive impairment from dementia, the combined model achieved an AUC of 0.972, compared with 0.933 for the blood biomarkers alone.
Of the individual biomarkers, CLU performed best at distinguishing normal cognition from cognitive impairment and mild cognitive impairment from dementia.
Researchers said the approach could potentially help identify people with Parkinson’s at greater risk of cognitive decline, particularly those with mild cognitive impairment who are at higher risk of progressing to 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].”
However, they said the results require confirmation 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.
