title: Effects of Risperidone and Galantamine Treatment on Alzheimer's Disease Biomarker Levels in Cerebrospinal Fluid.
abstract: 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).
  
  
  
  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, Aβ1-42, and Aβ42/40-ratio in CSF. The secondary aim was to test if baseline levels of these biomarkers are associated with the clinical course of NPS.
  
  
  
  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.
  
  
  
  Changes in levels of biomarkers between the two treatment groups did not differ significantly. Low baseline levels of Aβ1 - 42 was significantly associated with reduction of irritability at follow up. Low baseline levels of Aβ1-42, Aβ42/40, and P-Tau were significant correlates of reduction in appetite and eating disorders. CSF Aβ1-42 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).
  
  
  
  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 AD CSF biomarkers displayed correlations with specific NPS suggesting potential research questions to be pursued.
authors.affiliation: Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Victor
authors.initials: V
authors.lastname: Bloniecki
authors.affiliation: Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.|Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Dag
authors.initials: D
authors.lastname: Aarsland
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Gothenburg, Sweden.|Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cummings
authors.affiliation: Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Farshad
authors.initials: F
authors.lastname: Falahati
authors.affiliation: Department of Neurobiology, Karolinska Institute, Caring Sciences and Society (NVS), Center for Alzheimer Research, Division of Neurogeriatrics, Huddinge, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.affiliation: Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Freund-Levi
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D005500:Follow-Up Studies; D005702:Galantamine / Q000627:therapeutic use*; D006801:Humans; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D018967:Risperidone / Q000627:therapeutic use*; D016896:Treatment Outcome; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D002800:Cholinesterase Inhibitors; C054369:MAPT protein, human; D010446:Peptide Fragments; D011619:Psychotropic Drugs; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D005702:Galantamine; D018967:Risperidone
keywords: Biomarkers; dementia; galantamine; neuropsychiatric symptoms; risperidone