title: Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease.
abstract: OBJECTIVE
  The effects of (-)-phenserine (phenserine) and placebo/donepezil treatment on regional cerebral metabolic rate for glucose (rCMRglc) and brain amyloid load were investigated by positron emission tomography in 20 patients with mild Alzheimer's disease in relation to cerebrospinal fluid (CSF) and plasma biomarkers, and cognitive function.
  
  
  METHODS
  The first 3 months of the study was a randomized, double-blind, placebo-controlled phase, during which 10 patients received phenserine (30 mg/day) and 10 patients the placebo. Three to 6 months was an open-label extension phase, during which the placebo group received donepezil (5 mg/day) and the phenserine group remained on phenserine. After 6 months, all patients received phenserine treatment up to 12 months. The patients underwent positron emission tomography examinations to measure rCMRglc (8F-FDG) and amyloid load (11C-PIB) at baseline and after 3 and 6 months of the treatment. Neuropsychological and biomarker data were collected at the three times of positron emission tomography imaging.
  
  
  RESULTS
  Statistically significant effects on a composite neuropsychological test score were observed in the phenserine-treated group compared with the placebo and donepezil group at 3 and 6 months, respectively. Values of rCMRglc were significantly increased in several cortical regions after 3 months of phenserine treatment, compared with baseline, and correlated positively with cognitive function and CSF beta-amyloid 40 (Abeta40). Cortical Pittsburgh Compound B retention correlated negatively with CSF Abeta40 levels and the ratio Abeta/beta-secretase-cleaved amyloid precursor protein. In CSF, Abeta40 correlated positively with the attention domain of cognition.
  
  
  CONCLUSIONS
  Phenserine treatment was associated with an improvement in cognition and an increase in rCMRglc.
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Sweden.
authors.forename: Ahmadul
authors.initials: A
authors.lastname: Kadir
authors.forename: Niels
authors.initials: N
authors.lastname: Andreasen
authors.forename: Ove
authors.initials: O
authors.lastname: Almkvist
authors.forename: Anders
authors.initials: A
authors.lastname: Wall
authors.forename: Anton
authors.initials: A
authors.lastname: Forsberg
authors.forename: Henry
authors.initials: H
authors.lastname: Engler
authors.forename: Göran
authors.initials: G
authors.lastname: Hagman
authors.forename: Marie
authors.initials: M
authors.lastname: Lärksäter
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Bengt
authors.initials: B
authors.lastname: Långström
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010830:Physostigmine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015990:Placebo Effect; D049268:Positron-Emission Tomography; D016896:Treatment Outcome
chemical_list: D000682:Amyloid; D002800:Cholinesterase Inhibitors; D010830:Physostigmine; C092280:phenserine