Neuropsychiatric Correlates of Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease

Abstract

Background: The aim of this study was to explore the relationship between cerebrospinal fluid biomarkers and neuropsychiatric symptoms in people with Alzheimer’s disease. Psychosis, agitation, apathy and depression were assessed using standardised measures in 32 patients with mild Alzheimer’s disease. Methods: The levels of the 42-amino-acid form of β-amyloid (Aβ_1–42), tau and p-tau (phosphorylated at threonine 181) were quantified using the conventional enzyme-linked immunosorbent assay method. Results: Our result shows that apathy is significantly correlated with tau and p-tau but not with Aβ_1–42. There were no significant correlations between indices of psychosis/agitation,or depression and cerebrospinal fluid Aβ_1–42, tau or p-tau concentrations. Conclusion: Our finding suggests that apathy is associated with the level of neurofibrillary tangles in people with mild Alzheimer’s disease. In contrast, the overall levels of neurofibrillary tangles or amyloid plaques do not seem to be associated with depression or psychosis, indicating that other brain changes contribute to these symptoms.

Agitation in Dementia: Relation to Core Cerebrospinal Fluid Biomarker Levels

“…No significant correlation was found between agitation and Aβ 1-42 in the AD group. Other studies have also failed to find an association between agitation and Aβ 1-42 [18]. Although our result contradicts findings from a previous report that found a negative correlation between aggressive behavior and Aβ 1-42 [20], the current study did not include adjustment for severity of dementia, which might have contributed to this association.…”

“…Previous research has indicated that frontal lobe circuit dysfunction, possibly involving tau-mediated pathology, could be a cause of agitation in dementia [32]. Although our results are significant, a previous study comparing agitation in AD patients with CSF-biomarkers contradicts these findings [18]. Possible explanations for this discrepancy are the facts that the NPI subitem score for agitation was used to quantify agitation in that study, which is less sensitive as compared to CMAI, and that the study only included patients with mild AD not selected for BPSD.…”

“…In contrast, less is known about the relationship between these biomarkers and BPSD. In a recent study, apathy was shown to correlate with increased levels of both P-tau and T-tau in CSF, suggesting that apathy could be associated with increased amounts of NFTs in the brain [18]. The association between depression and AD biomarkers has also been studied, but no evidence that links depression with the presence of amyloid plaques or NFTs was found [18,19].…”

“…In a recent study, apathy was shown to correlate with increased levels of both P-tau and T-tau in CSF, suggesting that apathy could be associated with increased amounts of NFTs in the brain [18]. The association between depression and AD biomarkers has also been studied, but no evidence that links depression with the presence of amyloid plaques or NFTs was found [18,19]. Levels of CSF Aβ 1-42 have been shown to display a negative correlation with increased aggressive behavior in demented patients [20].…”

“…Levels of CSF Aβ 1-42 have been shown to display a negative correlation with increased aggressive behavior in demented patients [20]. Several studies indicate that NFTs and amyloid plaques could be involved in the pathological process causing BPSD but this has not been proven and further research is warranted [11,12,18,19,20]. Current pharmacological treatment options for agitation mainly include antipsychotics, which display modest efficacy and might be associated with severe cerebrovascular events [21,22].…”