Abstract
Objectives
Thailand is entering a super-aged society, resulting in a significant increase in the prevalence of
neurodegenerative diseases (NDDs) that leads to a growing socioeconomic burden. Addressing
this challenge requires a comprehensive approach that includes public health campaigns to
reduce risk factors, the development of care systems, and the promotion of research to alleviate
long-term impact. One promising strategy is the use of biomarkers for early diagnosis—prior to
symptom onset—enabling precision prevention either through emerging disease-modifying
therapies (DMTs) or through intensified management of individual risk profiles. This research
program aims to build national capacity for biomarker testing in Thai patients and prepare the
healthcare system for the implementation of biomarker-guided care in NDDs.
Material and Methods
The National Prion Disease Surveillance Program evaluated patients with suspected prion
disease through clinical assessments, cerebrospinal fluid (CSF) collection for biomarker testing,
and MRI interpretation by expert neuroradiologists. A related project on α-synuclein detection
using RT-QuIC tested three assay protocols on CSF samples from patients with Parkinsonian
syndromes. In the prospective cohort study Investigating Neurocognitive Disorders
Epidemiology (NCT06375213), participants were recruited from both a hospital memory clinic
and the general public. All participants underwent blood sampling for biomarkers—particularly
plasma phosphorylated tau217 (p-tau217)—cognitive testing, and staging by clinical severity. A
subset received PET scans, and participants are being followed annually if cognitively impaired
or every two years if cognitively normal. In year four, analysis focused on participants with mild
cognitive impairment (MCI) and mild dementia who had at least two years of follow-up.
Baseline biomarkers were assessed as predictors of cognitive decline using receiver operating
characteristics (ROC). Participants were divided into quartiles based on biomarker levels, and
linear mixed-effects models adjusted for age, sex, and education were used to estimate average
rates of cognitive decline. In a separate study to establish reference values for plasma
neurofilament light chain (NFL), 543 healthy individuals aged 19–89 were enrolled and analyzed
using the 95th percentile stratified by age group.
Results
The Prion Surveillance Project enrolled 65 patients from across Thailand, of whom 37 were
diagnosed with prion disease (33 RT-QuIC positive). None exhibited signs of transmissible prion
disease. The in-house synthesized α-synuclein RT-QuIC assay demonstrated over 80%
concordance with commercial standards. The cognitive cohort enrolled 391 participants: 235
cognitively normal, 131 with MCI, and 25 with dementia and now has 116 participants with
follow-up data. Of the 47 MCI and mild dementia participants who had at least two years of
observation, 8 participants (18.18%) declined more than 3 points per year on the Montreal
Cognitive Assessment (MoCA), 15 (31.91%) increased more than 1 point per year on the
Clinical Dementia Rating Scale – Sum of Boxes (CDR-SOB), and 19 (40.43%) showed
significant decline on either metric. The best predictor of MoCA decline was tau-PET (AUC =
0.91, 95% CI: 0.83–1.0), followed by plasma p-tau217 (AUC = 0.84, 95% CI: 0.72–0.96).
Similarly, tau-PET best predicted worsening of CDR-SOB (AUC = 0.86, 95% CI: 0.73–0.98),
followed by p-tau217 (AUC = 0.79, 95% CI: 0.66–0.93). When considering either cognitive
measure, tau-PET showed the highest overall predictive value (AUC = 0.94, 95% CI: 0.86–1.0),
followed by p-tau217 (AUC = 0.83, 95% CI: 0.71–0.95). In mixed-effects models, participants in
the highest quartile of plasma p-tau217 (≥15.9 pg/mL) showed an average MoCA decline of 6.98
points and CDR-SOB increase of 4.25 over three years, compared with declines of 1.92 and 0.88,
respectively, in those with lower levels. In the NFL reference study, plasma NFL concentrations
were found to increase with age, although differences between some adjacent age groups were
not statistically significant. The 95th percentile values for plasma NFL in individuals aged 19–
50, 51–60, 61–70, and 71–90 were 11.6, 16.1, 22.0, and 37.0 pg/mL, respectively. Preparations
are currently underway for a nationwide implementation of biomarker-based dementia
prevention and care, with sample collection expected to begin in year five.
Conclusion
In conclusion, by the fourth year of this initiative, no suspected outbreaks of transmissible prion
disease were detected. The Investigating Neurocognitive Disorders Epidemiology cohort
successfully enrolled participants as planned. Among those with MCI and early dementia, tauPET was the most accurate predictor of cognitive decline, though plasma p-tau217 performed
nearly as well and shows strong potential as a scalable screening tool. Reference values for
plasma NFL in the Thai population were consistent with international findings, supporting their
use in clinical and research settings.
