The role of CSF biomarkers in the diagnostic work-up of mixed vascular-degenerative dementia.

Low average specificity levels of 48% for clinical diagnosis of possible Alzheimer's disease (AD) reflect the overlap of clinical profiles between AD and non-AD dementias. Should diagnostic errors occur, they most likely involve one of the other primary dementias, mixed pathologies that include a vascular component, or uncertainties that are associated with early diagnosis. Vascular dementia (VaD) is overdiagnosed when a routine brain MRI or CT scan is used in the context of standard clinical diagnostic criteria, meanwhile denying significant neurodegenerative co-pathology. A promising approach for increasing diagnostic accuracy is the use of biochemical markers (biomarkers) that are present in the cerebrospinal fluid (CSF). The CSF biomarkers ß-amyloid protein of 42 amino acids (Aß(1-42)), total tau protein (T-tau), and tau phosphorylated at threonine 181 (P-tau(181P)) are well validated. A combined analysis of these biomarkers is of help to discriminate AD from non-AD dementias (including VaD), reaching sensitivity and specificity levels that exceed 80%. Moreover, the added value of CSF biomarkers could lie within those cases in which the clinical diagnostic work-up is not able to discriminate between AD or a non-AD dementia. In case of doubt between VaD or mixed AD-VaD pathology in dementia patients, the determination of CSF Aß(1-42), T-tau and P-tau(181P) levels is of help to confirm or exclude the AD component in the pathophysiology of the dementia syndrome.