Background: Cerebrospinal fluid (CSF) biomarkers are routinely used for the differential diagnosis of rapidly progressive dementia, but are also affected by patients' characteristics.
Objective: To assess if stratification by age, sex, and genetic risk factors improves the accuracy of cerebrospinal fluid (CSF) biomarkers in patients with rapidly progressive dementia.
Methods: 1,538 individuals with sporadic Creutzfeldt-Jakob disease (CJD), 173 with classic Alzheimer's disease (cAD), 37 with rapidly progressive Alzheimer's disease (rpAD), and 589 without signs of dementia were included in this retrospective diagnostic study. The effect of age, sex, PRNP codon 129, and APOE genotype on CSF levels of tau, p-tau, Aβ1-42, and Aβ1-40 values measured at time of diagnostic work-up was assessed.
Results: Tau was a better marker for the differentiation of CJD and rpAD in older (AUC:0.97; 95% CI:0.96-1.00) than in younger (AUC:0.91; 95% CI:0.87-0.94) patients as tau levels increased with age in CJD patients, but not in rpAD patients. PRNP codon 129 and APOE genotype had complex effects on biomarkers in all diseases, making stratification by genotype a powerful tool. In females (AUC:0.78; 95% CI:0.65-0.91) and patients older than 70 (AUC:0.78; 95% CI:0.62-0.93), tau was able to differentiate with moderate accuracy between cAD and rpAD patients.
Conclusion: Implementation of stratum-specific reference ranges improves the diagnostic accuracy of CSF biomarkers for the differential diagnosis of rapidly progressive dementia. Diagnostic criteria developed for this setting have to take this into account.
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