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O4‐08‐04: Changes in Outpatient Costs Following Screening and Diagnosis of Cognitive Impairment
Author(s) -
McCarten John R.,
Anderson Pauline,
Kuskowski Michael A.,
Jonk Yvonne,
Dysken Maurice W.
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.08.057
Subject(s) - medicine , dementia , poisson regression , cognitive impairment , medical record , outpatient clinic , ambulatory care , health care , cognition , disease , emergency medicine , family medicine , gerontology , psychiatry , population , economics , economic growth , environmental health
restoring defective cellular metal ion homeostasis, normalizes synaptic function via an activity on various proteins and signaling cascades, including GSK3ß . We have now looked for changes in neuronal markers in APP/PS1 AD mice and also investigated the effects of PBT2 in an animal model for HD, a condition which shares pathological features with AD including evidence of glutamate excitotoxicity. Methods: Transgenic AD (APP/PS1)mice were treated with 30mg/kg PBT2 for 11 days and brain tissues assayed for levels of markers associated with neuronal function and plasticity. Separately, R6/2 HD mice were treated with PBT2 for 14 weeks and examined for alterations in behaviour, lifespan and brain anatomy. In a further in vitro experiment, we examined the effect of PBT2 upon glutamate excitotoxicity. Results: In APP/PS1 mice, levels of NMDAr, Trkb and other markers of neuronal function were restored to those seen in wild-type animals. The level of synaptophysin, markedly reduced in Tg mice, was also restored with PBT2 treatment, mirrored by large and significant increases in the density of hippocampal CA1 dendritic spines. PBT2 also prevented the excitotoxic effects of excess glutamate in primary cortical neurons. This protective effect of PBT2 was inhibited by the potent chelator diamsar demonstrating that this effect is dependent on metal delivery rather than on NMDAr inhibition. In R6/2 mice, PBT2 had significant beneficial effects on motor function, behaviour and lifespan accompanied by a marked reduction in striatal atrophy indicated by significant reduction in lateral ventricle volume compared with untreated controls. Conclusions: PBT2 has potent neurotrophic and neuroprotective effects in vitro and in vivo. The beneficial effects of PBT2 seen in R6/2 mice reflect a similar neuroprotective mechanism to that identified for AD indicating the potential of this drug for therapeutic application in both conditions.