The generalizability of proposed reference values for plasma neurofilament light chain in cognitively healthy adults in Thailand
Juthamas Rianaree, Prakit Anukoolwittaya, Akarin Hiransuthikul, Pasin Hemachudha, Thiravat Hemachudha, Poosanu Thanapornsangsuth- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Despite being an established biomarker for quantifying neuroaxonal injury in research, the clinical utility of neurofilament light chain (NFL) for assessing individual patients is limited, primarily due to the confounding effect of aging on its levels. Although many studies reported age‐specific cutoff values in neurologically healthy population of European descent in high‐income countries, evidence suggests that the value of neurodegenerative biomarkers may differ in ethnically and socioeconomically underrepresented populations. In this study, we aimed to evaluate the acceptability of the reported NFL cutoff values for local clinical use by examining specimens from healthy Thai cohorts.
Method
This study enrolled participants without neurological disorder and normal cognitive examination from two distinct cohorts in Bangkok, Thailand, ranging in age from 40 to 90 years old. Plasma levels of NFL were quantified using the single molecule array. By utilizing reference data from previous studies (Simrén et al., 2022; Bornhorst et al., 2022), the proportion of participants exceeding the proposed cutoff values were estimated and compared to the expected values. Furthermore, the cohort was stratified by age group and methods similar to prior studies were employed to determine age‐specific cutoff values.
Result
One hundred and three participants were included, comprising of 69 females (67%), with a median age of 65.4 years (interquartile range (IQR): 56.7, 70.3) and a cognitive z‐score of 0.11 (IQR: ‐0.44, 0.63). Using the reference threshold from prior studies, plasma NFL were elevated in 4 participants (3.9%, 95% confidence interval: 1.0‐9.6%) which is consistent with the expected prevalence of 5% (as 95th percentile cutoffs were used). Subsequently, we determined age‐specific plasma NFL cut‐off values for each decade through quantile regression, values ranging from 7.2 pg/mL for 40‐50 years to 58.2 pg/mL for >80 years.
Conclusion
Our initial findings suggest that the previously established cutoffs for plasma NFL may be applicable in Thailand. Nonetheless, further studies with a larger and more diverse sample size may be necessary in order to fully validate the generalizability of these cutoffs and potentially establish more specific thresholds for local use.