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Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease
Author(s) -
Kadir Ahmadul,
Andreasen Niels,
Almkvist Ove,
Wall Anders,
Forsberg Anton,
Engler Henry,
Hagman Göran,
Lärksäter Marie,
Winblad Bengt,
Zetterberg Henrik,
Blennow Kaj,
Långström Bengt,
Nordberg Agneta
Publication year - 2008
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21345
Subject(s) - donepezil , placebo , medicine , pittsburgh compound b , positron emission tomography , cognitive decline , neuropsychological test , cardiology , alzheimer's disease , neuropsychology , cognition , nuclear medicine , pathology , dementia , disease , psychiatry , alternative medicine
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 (30mg/day) and 10 patients the placebo. Three to 6 months was an open‐label extension phase, during which the placebo group received donepezil (5mg/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 (18F‐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 β‐amyloid 40 (Aβ40). Cortical Pittsburgh Compound B retention correlated negatively with CSF Aβ40 levels and the ratio Aβ/β‐secretase–cleaved amyloid precursor protein. In CSF, Aβ40 correlated positively with the attention domain of cognition. Interpretation Phenserine treatment was associated with an improvement in cognition and an increase in rCMRglc. Ann Neurol 2008