Neuropsychological and behavioural correlates of CSF biomarkers in dementia

Abstract

To improve clinical, neuropsychological and behavioural characterisation of the cerebrospinal fluid (CSF) biomarkers β-amyloid (1-42) protein (Aβ42), protein tau (tau) and tau phosphorylated at threonine 181 (P-tau181) across diagnostic dementia categories, a prospective study was set up. Patients with probable Alzheimer's disease (AD) ( n = 201), AD with cerebrovascular disease (CVD) (AD + CVD) ( n = 33), frontotemporal dementia (FTD) ( n = 27), dementia with Lewy bodies (DLB) ( n = 22) and healthy controls ( n = 148) were included. All patients underwent neuropsychological examination and behavioural assessment by means of a battery of behavioural assessment scales. CSF was obtained by lumbar puncture and levels of Aβ42, tau and P-tau181 were determined with commercially available ELISA kits. Negative correlations between CSF Aβ42 levels and aggressiveness (Spearman: r = −0.223; p = 0.002) and positive correlations with age at inclusion ( r = 0.195; p = 0.006), age at onset ( r = 0.205; p = 0.003) and MMSE scores ( r = 0.198; p = 0.005) were found in AD. In AD + CVD, CSF Aβ42 levels were correlated with MMSE ( r = 0.482; p = 0.006), Hierarchic Dementia Scale ( r = 0.503; p = 0.017) and Boston Naming Test ( r = 0.516; p = 0.012) scores. In controls, age was positively correlated with CSF tau ( r = 0.465; p < 0.001) and P-tau181 levels ( r = 0.312; p < 0.001). CSF tau and P-tau181 levels correlated significantly in all groups, whereas CSF Aβ42 correlated with tau and P-tau181 levels in healthy controls only. Negative correlations between CSF Aβ42 levels and aggressiveness were found in AD patients. CSF Aβ42 seems to be a stage marker for AD (+/−CVD) given the positive correlations with neuropsychological test results suggesting that CSF Aβ42 might be of help for monitoring disease progression. Different correlations between age and CSF biomarker levels were obtained in healthy controls compared to AD patients, indicating that AD-induced pathophysiological processes change age-dependent regulation of CSF biomarker levels.