Karen Maertens

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 (Abeta42), protein tau (tau) and tau phosphorylated at threonine 181 (P-tau181) across diagnostic dementia categories, a prospective study was set up. Patients with probable Alzheimers 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 Abeta42, tau and P-tau181 were determined with commercially available ELISA kits. Negative correlations between CSF Abeta42 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 Abeta42 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 Abeta42 correlated with tau and P-tau181 levels in healthy controls only. Negative correlations between CSF Abeta42 levels and aggressiveness were found in AD patients. CSF Abeta42 seems to be a stage marker for AD (+/-CVD) given the positive correlations with neuropsychological test results suggesting that CSF Abeta42 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.

Behavioural and neuropsychological correlates of frontal lobe features in dementia

BACKGROUND In order to characterize frontal lobe features and their behavioural and cognitive correlates across diagnostic categories, we performed a cross-sectional analysis of behavioural and neuropsychological data from a large, prospective Belgian study on behavioural and psychological signs and symptoms of dementia (BPSD). METHOD Patients with probable Alzheimers disease (AD) (n=170), frontotemporal dementia (FTD) (n=28), mixed dementia (MXD) (n=29) and dementia with Lewy bodies (DLB) (n=21) were included and underwent neuropsychological and behavioural assessment by means of a battery of tests and scales. Frontal lobe symptoms were quantified by means of the Middelheim Frontality Score (MFS). RESULTS In AD (and to a lesser extent in MXD), MFS total scores were negatively correlated with scores on MMSE (Spearman: r=-0.36, p<0.001) and a Verbal Fluency Task (r=-0.38, p<0.001) and were associated with increased severity and frequency of psychosis (r=0.24, p<0.01), activity disturbances (r=0.44, p<0.001) and aggressiveness (r=0.43, p<0.001). In DLB, MFS total scores were negatively correlated with MMSE scores (r=-0.50, p=0.020). No associations were found in FTD patients. CONCLUSIONS A cross-sectional analysis of frontal lobe features, behavioural characteristics and neuropsychological data demonstrated that, in AD (and to a lesser extent in MXD) patients, frontal lobe symptoms were associated with more pronounced cognitive deficits (of frontal origin), with increased severity and frequency of agitated and aggressive behaviour, and with increased severity of psychosis and depressive symptoms. Given the small sample sizes of the DLB and FTD patient groups, negative findings in these patient groups should be interpreted cautiously.

Correlations between cognitive, behavioural and psychological findings and levels of vitamin B_{12} and folate in patients with dementia: a prospective study

Associations between low levels of folate and vitamin B12 and cognitive impairment in patients with dementia have been reported. Some studies revealed correlations between low levels of vitamin B12 and behavioural and psychological signs and symptoms of dementia (BPSD) in Alzheimers disease (AD) patients. Given the lack of studies in frontotemporal dementia (FTD) and on folate and given the methodological shortcomings of former publications, we set up a prospective study.