CSF Amyloid and Tau Biomarkers Distinguish Mixed from Vascular Dementia by Identifying Alzheimer’s Disease Co-Pathology

Background and Objectives: Vascular dementia (VaD) and mixed dementia (MD) represent prevalent causes of cognitive decline in the elderly, as they share similar pathological pathways and clinical features. Distinguishing between these two conditions remains a challenge, due to their frequent clinical and neuroimaging overlap. Nevertheless, it is important from a prognostic perspective. Materials and Methods: The study comprised 114 participants, including patients with VaD (n = 33), MD (n = 26), Alzheimer’s disease (AD; n = 26), and 29 cognitively healthy controls (C). We evaluated routinely used cerebrospinal fluid (CSF) biomarkers (total tau, p-tau181, Aβ1-42) and their ratios to assess inter-group differences, diagnostic accuracy, and correlations with cognitive score. Results: Patients with MD demonstrated significantly higher levels of t-tau and p-tau181, and lower levels of Aβ1-42, compared to VaD (p < 0.004 for all analyses). With the exception of p-tau181/t-tau, all calculated ratios enabled differentiation between these groups. ROC analysis confirmed the high diagnostic accuracy of CSF Aβ1-42 and t-tau (AUC 0.82 and 0.79 respectively) for detecting AD pathology in dementia patients. Furthermore, the t-tau/Aβ1-42, p-tau181/Aβ1-42 ratios were the most effective in differentiating AD-related from vascular pathologies (AUC 0.78 and 0.80 respectively), and in differentiating MD from VaD (AUC 0.79 and 0.77 respectively). A significant correlation was observed between CSF biomarkers (especially tau markers) and cognitive impairment severity. Conclusions: CSF biomarkers effectively differentiate mixed from vascular dementia by identifying underlying AD pathology independent of the clinical phenotype. This supports the use of CSF biomarkers in clinical practice to reveal the neurodegenerative component in patients with cerebrovascular disease, which is of fundamental importance for emerging disease-modifying treatment strategies in mixed neuropathologies.