Neuropsychological and behavioural correlates of CSF biomarkers in dementia

To improve clinical, neuropsychological and behavioural characterisation of the cerebrospinal fluid (CSF) biomarkers beta-amyloid((1-42)) protein (A beta 42), protein tau (tau) and tau phosphorylated at threonine 181 (P-tau181) across diagnostic dementia categories, a prospective study was setup. 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 A beta 42, tau and P-tau181 were determined with commercially available ELISA kits. Negative correlations between CSF A beta 42 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 A beta 42 levels were correlated with MMSE (r = 0.482; p = 0.006), Hierarchic Dementia Scale (r = 0.503; p = 0.0 17) 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 A beta 42 correlated with tau and P-tau181 levels in healthy controls only. Negative correlations between CSF A beta 42 levels and aggressiveness were found in AD patients. CSF AP42 seems to be a stage marker for AD (+/-CVD) given the positive correlations with neuropsychological test results suggesting that CSF A beta 42 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. (C) 2005 Elsevier Ltd. All rights reserved.