Neurochemical and genetic correlates of behavioural and psychological signs and symptoms of dementia

In order to trace for correlates between biological and genetic markers and BPSD, we set up a prospective, longitudinal study on well-characterised patients with several forms of degenerative and mixed vascular-degenerative dementias. All patients underwent behavioural assessments at baseline and semi-annually thereafter. A lumbar puncture was performed at baseline as well.; Analysis of behavioural data demonstrated that dementia should not be regarded as a single nosological entity as disease-specific behavioural profiles were identified. For some forms of dementia like frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB), specific BPSD are almost pathognomonic. We therefore developed the Middelheim Frontality Score (MFS), a clinical and behavioural assessment tool that measures frontal lobe features. The validation study demonstrated that the MFS reliably discriminated FTD from Alzheimer's disease (AD) patients with a sensitivity and specificity of almost 90%.; In order to trace for neurochemical correlates of BPSD, we determined all dopamine and serotonin metabolites in cerebrospinal fluid (CSF) of patients with BPSD. The CSF homovanillic acid (HVA)/5-hydroxyindoleacetic acid (5HIAA) ratio reflecting tonic serotonergic modulation of dopaminergic activity, was negatively associated with dementia severity in both AD and FTD patient groups. The present study demonstrated that the neurochemical substrates of BPSD depended on etiological diagnoses of dementia as several disease-specific correlations between BPSD and CSF monoaminergic metabolites were found. High CSF 3,4-dihydroxyphenylacetic acid (DOPAC) levels were associated with agitated and aggressive behaviour in FTD patients and were able to predict future aggressive and agitated behaviour.; In order to further characterise the neurochemical correlates of BPSD, we performed a genotyping of several dopaminergic and serotonergic neurotransmitter-related genes and identified several new and possibly relevant associations with BPSD in AD and FTD patients. Although these findings await confirmation, we hypothesize that certain neurotransmitter-related polymorphisms may lead to altered function of neurotransmitter systems contributing to the pathophysiology of BPSD. Our genetic and neurochemical correlation studies support this hypothesis.