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Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease.

Journal article
Authors Ahmadul Kadir
Niels Andreasen
Ove Almkvist
Anders Wall
Anton Forsberg
Henry Engler
Göran Hagman
Marie Lärksäter
Bengt Winblad
Henrik Zetterberg
Kaj Blennow
Bengt Långström
Agneta Nordberg
Published in Annals of neurology
Volume 63
Issue 5
Pages 621-31
ISSN 1531-8249
Publication year 2008
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 621-31
Language en
Links dx.doi.org/10.1002/ana.21345
Keywords Aged, Alzheimer Disease, drug therapy, metabolism, radionuclide imaging, Amyloid, metabolism, Brain, drug effects, metabolism, radiation effects, Cholinesterase Inhibitors, administration & dosage, Double-Blind Method, Female, Humans, Male, Physostigmine, administration & dosage, analogs & derivatives, Placebo Effect, Positron-Emission Tomography, Treatment Outcome
Subject categories Medical and Health Sciences

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. INTERPRETATION: Phenserine treatment was associated with an improvement in cognition and an increase in rCMRglc.

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