O1-05-01: Biomarker profiles and their relationship to cognitive and other clinical variables in Alzheimer's disease

Cerebrospinal fluid (CSF) biomarkers Amyloid-Beta 1–42 (Aβ1–42), Tau and Phosphorylated-Tau (P-Tau) are diagnostic markers for Alzheimer's disease (AD). Still, within AD patients large variations in levels of these biomarkers exist. We aimed to investigate the relationship between CSF biomarker profiles and cognitive and clinical variables in AD. 127 AD patients were included. Age, sex, education, disease duration and APOE genotype were recorded. Cognitive functions were assessed using Mini Mental State Examination (MMSE), Digit Span, Visual Association Test (VAT), VAT object-naming, category fluency and Trail Making Test (TMT). In CSF, levels of Aβ1–42, Tau and P-Tau were measured. K-means cluster analysis was performed with Aβ1–42, Tau and P-Tau as variables to obtain 3 clusters. This analysis assigns patients to groups to obtain a maximal difference in cluster variables between clusters and a minimal difference between patients within a cluster. ANOVA's were performed with CSF-cluster as independent variable, age, sex and education as covariates and clinical variables as dependent variables. After categorization using K-means cluster analysis, on average, all groups had abnormal biomarker levels. The “Modest” group consisted of 43 patients (34%) with relatively high levels of Aβ1–42and low levels of Tau and P-Tau. The “Extreme” group was made up of 21 patients (16%) with low levels of Aβ1–42and very high levels of Tau and P-Tau. The “Typical” group was made up of 63 patients (50%) with levels of Aβ1–42, Tau and P-Tau which were in between those of the other groups. Patients in the “Extreme” group performed worse on TMT parts A and B and on VAT than patients in the “Typical” and “Modest” groups. No differences between groups in disease severity or any of the other clinical variables were found. In comparison to AD patients with moderate CSF profiles, AD patients with extremely high Tau and P-Tau levels and a relatively low level of Aβ1–42 showed a distinct cognitive profile with more severe impairments of memory, mental speed and executive functions, which cannot be explained by age, disease duration or severity.