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Kadir, A. et al. Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease. Ann. Neurol. 63, 621-631

Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Sweden.
Annals of Neurology (Impact Factor: 11.91). 05/2008; 63(5):621-31. DOI: 10.1002/ana.21345
Source: PubMed

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

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    • "We would like to thank Dr. Niels Andreasen and Dr. Lennart Minthon for generously providing the samples included in the SATS-study [9] and Research Nurse Marie Lärksäter for her excellent assistance in collecting the CSF samples of the phenserine study [37]. "
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    • "First, the limited sample size in the DNMP study likely reduced the statistical power to accurately identify treatment differences, and consequently the effects attributed to cholinesterase inhibition may be partially related to group differences. Second, although preclinical and clinical studies with phenserine support memory enhancement [54] [56], phenserine clinical development was ultimately halted following the failure of an initial phase III clinical trial likely related to methodological problems that were later independently verified [85]. Nonetheless, the use of an approved acetylcholinesterase inhibitor would afford even greater validation of the canine model [1]. "
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