The study was published online Feb. 21 in the early edition of the Proceedings of the National Academy of Sciences. The findings may provide another piece of the puzzle in figuring out how tau proteins can poison nerve cells in the brain.

Akt is known to increase cancer cell survival capability and has become a target in the development of some cancer-inhibitor drugs. The abnormal accumulation of tau protein tangles kills nerve cells and is considered one of the hallmarks of Alzheimer's disease.

This study describes for the first time a new function for the cancer-related protein Akt “ one that may help promote Alzheimer's disease pathology, said lead author Chad Dickey, PhD, assistant professor of molecular pharmacology and physiology at USF. We found that increased amounts of Akt may prevent the removal of abnormal proteins, such as tau, causing these proteins to accumulate and disrupt the balance within the cells.

While this Akt-induced imbalance might result in cancer cells continuing to divide uncontrollably, Dr. Dickey suggests it likely has a different effect in Alzheimer's disease. The nerve cells may try to divide in the brain, but cannot, and therefore die, he said. Thus regulating levels of Akt, rather than its activity, may be beneficial to sufferers of diseases of aging, such as cancer, Alzheimer's and even diabetes.

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While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose levels appears to fall on a continuum and olanzapine appears to have a greater association than some other atypical antipsychotics. Physicians should consider the risks and benefits when prescribing olanzapine to patients with an established diagnosis of diabetes mellitus, or who have borderline increased blood glucose level. Patients taking olanzapine should be monitored regularly for worsening of glucose control. Persons with risk factors for diabetes who are starting on atypical antipsychotics should undergo baseline and periodic fasting blood glucose testing. Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing.

Undesirable alterations in lipids have been observed with olanzapine use. Clinical monitoring, including baseline and follow-up lipid evaluations in patients using olanzapine, is advised. Significant, and sometimes very high, elevations in triglyceride levels have been observed with olanzapine use. Modest mean increases in total cholesterol have also been seen with olanzapine use.

Potential consequences of weight gain should be considered prior to starting olanzapine. Patients receiving olanzapine should receive regular monitoring of weight.

As with all antipsychotic medications, a rare and potentially fatal condition known as NMS has been reported with Zyprexa. If signs and symptoms appear, immediate discontinuation is recommended. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.

Also, as with all antipsychotic treatment, prescribing should be consistent with the need to minimize Tardive Dyskinesia (TD). The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.

The most common treatment-emergent adverse event associated with Zyprexa in placebo-controlled, short-term schizophrenia and bipolar mania trials was somnolence. Other common events were dizziness, weight gain, personality disorder (COSTART term for nonaggressive objectionable behavior), constipation, akathisia, postural hypotension, dry mouth, asthenia, dyspepsia, increased appetite and tremor.

Full prescribing information, including a boxed warning, is available at www.zyprexa.

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