Blood Biomarker NfL May Predict Cognitive Decline
UK researchers study neurofilament light chain and p-tau181 proteins
Levels of neurofilament light chain (NfL) protein in the bloodstream of people with Parkinson’s disease can independently predict cognitive decline, a recent study suggests.
Although p-tau181 concentration, a biomarker in Alzheimer’s disease, which is the most common cause of dementia, was higher in Parkinson’s patients, links to cognitive performance were not found.
NfL may serve as a non-invasive biomarker of cognitive progression in Parkinson’s, the researchers suggested. Further studies with larger groups of patients over longer periods are needed to establish and validate NfL cut-offs that can be useful in clinical practice, they recommended.
The study, “Plasma p-tau181, neurofilament light chain and association with cognition in Parkinson’s disease,” was published in the journal npj Parkinson’s Disease.
In addition to motor symptoms, Parkinson’s disease is marked by cognitive impairment, including dementia. As such, early identification of Parkinson’s patients who will develop cognitive problems has critical clinical and research implications.
To predict cognitive progression in Parkinson’s, most studies have focused on the value of clinical characteristics, imaging scans, and analysis of cerebrospinal fluid (CSF), the clear liquid surrounding the brain and spinal cord.
However, there is still an unmet need for reliable, non-invasive biomarkers to predict the progression of cognitive impairment in Parkinson’s.
Researchers at the U.K.’s King’s College London investigated two potential non-invasive bloodstream biomarkers for cognitive performance in people with Parkinson’s: p-tau181 and NfL.
Measuring p-tau181 levels in CSF helps support a diagnosis of Alzheimer’s, while NfL, a non-specific biomarker reflecting nerve damage, has been shown to be higher in CSF of Parkinson’s patients with worse cognitive impairment and motor function.
The team recruited 94 adults with Parkinson’s disease plus 63 age-matched healthy controls. At the study’s start (baseline), no cognitive differences were found between patients and controls based on scores from a mini-mental state examination (MMSE). Tests measured p-tau181 and NfL in blood plasma, the liquid portion of blood without cells that still contains clotting factors.
Baseline blood tests revealed significantly higher levels of p-tau181 in Parkinson’s patients compared to controls after correcting for age and sex. In contrast, plasma levels of NfL at baseline did not differ between the two groups.
Among Parkinson’s patients, higher baseline plasma NfL levels were associated with lower (worse) baseline MMSE scores after adjusting for age, sex, and years of education. However, there was no link between p-tau181 and MMSE at baseline, or between p-tau181 and NfL concentrations and non-motor symptoms.
Higher baseline NfL concentration also was associated with a longer disease duration, but not disease severity, by Hoehn and Yahr stages. Baseline p-tau181 and disease duration were not related.
In a subgroup of 47 Parkinson’s patients with up to two years of follow-up, high baseline plasma NfL level was associated with a decline in MMSE over time after adjusting for age, sex, and education. Each picogram per mL unit increase in plasma NfL at baseline predicted an annual decline of -0.036 MMSE points.
The team found no connection between baseline plasma p-tau181 concentration and MMSE cognitive changes over time.
Encouraging results
“Our results are encouraging and pave the way for the use of plasma NfL as non-invasive and feasible predictive biomarker of cognitive impairment in [Parkinson’s disease],” the researchers wrote.
“Further studies with larger sample size and longer longitudinal follow-up are needed in order to clarify the role of plasma p-tau181 in [Parkinson’s disease],” researchers added, “and to establish and validate plasma NfL cut-offs that can be used in clinical practice.”
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