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PBT2 Rapidly Improves Cognition in Alzheimer's Disease: Additional Phase II Analyses
Open accessAbstract
PBT2 is a copper/zinc ionophore that rapidly restores cognition in mouse models of Alzheimer's disease (AD). A recent Phase IIa double-blind, randomized, placebo-controlled trial found that the 250 mg dose of PBT2 was well-tolerated, significantly lowered cerebrospinal fluid (CSF) levels of amyloid-beta42, and significantly improved executive function on a Neuro-psychological Test Battery (NTB) within 12 weeks of treatment in patients with AD. In the post-hoc analysis reported here, the cognitive, blood marker, and CSF neurochemistry outcomes from the trial were subjected to further analysis. Ranking the responses to treatment after 12 weeks with placebo, PBT2 50 mg, and PBT2 250 mg revealed that the proportions of patients showing improvement on NTB Composite or Executive Factor z-scores were significantly greater in the PBT2 250 mg group than in the placebo group. Receiver-operator characteristic analyses revealed that the probability of an improver at any level coming from the PBT2 250 mg group was significantly greater, compared to placebo, for Composite z-scores (Area Under the Curve [AUC] =0.76, p=0.0007), Executive Factor z-scores (AUC =0.93, p=1.3 x 10(-9)), and near-significant for the ADAS-cog (AUC =0.72, p=0.056). There were no correlations between changes in CSF amyloid-beta or tau species and cognitive changes. These findings further encourage larger-scale testing of PBT2 for AD.
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Metadata
- Authors
- Faux, N. G., Ritchie, C. W., Gunn, A., Rembach, A., Tsatsanis, A., Bedo, J., Harrison, J., Lannfelt, L., Blennow, K., Zetterberg, H., Ingelsson, M., Masters, C. L., Tanzi, R. E., Cummings, J. L., Herd, C. M., & Bush, A. I.
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2010-04-01
- Volume
- 20
- Issue
- 2
- Pages
- 509-516
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2127914798
- Cited by
- 405
- References
- 20
- FWCI
- 22.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Faux, N. G., Ritchie, C. W., Gunn, A., Rembach, A., Tsatsanis, A., Bedo, J., Harrison, J., Lannfelt, L., Blennow, K., Zetterberg, H., Ingelsson, M., Masters, C. L., Tanzi, R. E., Cummings, J. L., Herd, C. M., & Bush, A. I. (2010). PBT2 Rapidly Improves Cognition in Alzheimer's Disease: Additional Phase II Analyses. Journal of Alzheimer's Disease. https://doi.org/10.3233/jad-2010-1390
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