Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease.
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.
Kadir
Ahmadul
A
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Sweden.
Andreasen
Niels
N
Almkvist
Ove
O
Wall
Anders
A
Forsberg
Anton
A
Engler
Henry
H
Hagman
Göran
G
Lärksäter
Marie
M
Winblad
Bengt
B
Zetterberg
Henrik
H
Blennow
Kaj
K
Långström
Bengt
B
Nordberg
Agneta
A
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
D000682:Amyloid; D002800:Cholinesterase Inhibitors; D010830:Physostigmine; C092280:phenserine