Effects of Risperidone and Galantamine Treatment on Alzheimer's Disease Biomarker Levels in Cerebrospinal Fluid

Background: Treatment for neuropsychiatric symptoms (NPS) in dementia is insufficient. Antipsychotics and acetylcholinesterase inhibitors are used generating symptomatic improvements in behavior and cognition, but few studies have investigated their effect on Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF). Objective: This is a secondary analysis based on an earlier clinical trial comparing the treatment effects on NPS. The aim of this study was to examine whether treatment with risperidone and galantamine affect levels of the biomarkers T-Tau, P-Tau, A beta(1-42), and A beta(42/40)-ratio in CSF. The secondary aim was to test if baseline levels of these biomarkers are associated with the clinical course of NPS. Methods: 83 patients (mean + SD 77.9.6 +/- 7.7 years) with dementia and NPS were randomized to galantamine (n = 44) or risperidone (n = 39) treatment. CSF samples were collected at baseline and after 12 weeks. Results: Changes in levels of biomarkers between the two treatment groups did not differ significantly. Low baseline levels of A beta(1-42) was significantly associated with reduction of irritability at follow up. Low baseline levels of A beta(1-42), A beta(42/40), and P-Tau were significant correlates of reduction in appetite and eating disorders. CSF A beta(1-42) levels in patients treated with risperidone were significantly decreased at follow up, showing an 8% (40 pg/mL) reduction as compared with baseline (p = 0.03). Conclusions: Our results suggest that risperidone may affect the CSF profile of AD biomarkers indicating more amyloid pathology. Treatment with galantamine did not affect the CSF biomarkers in any direction. The ADCSF biomarkers displayed correlations with specific NPS suggesting potential research questions to be pursued.