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Mice Research Suggests Common Drugs May Lower Risk of Alzheimer’s
Led by Giulio Maria Pasinetti, M.D., Ph.D., researchers at The Mount Sinai Medical Center used a computer algorithm to screen 1,600 commercially available medications to assess their impact on the brain accumulation of beta-amyloid.
The study, published online in the journal PLoS One, researchers found that currently available medications prescribed for conditions such as hypertension, depression, and insomnia were found to either to block or to enhance the accumulation of beta-amyloid, the component of amyloid plaques.
Beta-amyloid is a protein that abnormally accumulates in the brain of Alzheimer’s disease and is believed to be responsible for neurodegeneration.
“This line of investigation will soon lead to the identification of common medications that might potentially trigger conditions associated with the prevention, or conversely the onset, of Alzheimer’s disease,” said Pasinetti.
“They may be a novel reference for physicians to consider when prescribing the most appropriate drug, particularly in subjects at high risk for Alzheimer’s disease.”
For the study, Pasinetti and his colleagues administered these drugs in mice that were genetically engineered to develop the hallmark amyloid plaques associated with Alzheimer’s disease.
After six months of treatment with blood pressure medicines, amyloid plaques and neurodegeneration were significantly reduced in the mice.
Carvedilol is one medicine that shows clinical promise – the drug is now under clinical investigation in Alzheimer ‘s disease with the intent to slow down memory deterioration.
“In recent years, amyloid plaques have become one of the main focal points in the search to understand and to treat Alzheimer’s disease,” said Pasinetti. “Thus, identifying novel drug treatments that prevent harmful beta-amyloid generation will help in the development of treatments for Alzheimer’s disease.
“For example, one very exciting finding of our study is that Carvedilol, already approved for treatment of hypertension, may immediately become a promising drug for the treatment of Alzheimer’s as well.”
Several limitations accompany the research, with the authors noting that studies must be immediately verified in human-safety studies.
Pasinetti hopes these findings will lead to multiple clinical trials in the future to identify preventive drugs, which will need to be prescribed at tolerable dosages.
“If we can repurpose drugs currently used for different indications, such as lowering blood pressure, this could have dramatic implications for this population,” said Pasinetti.
Source: The Mount Sinai Hospital / Mount Sinai School of Medicine
Brain Scans May Someday Help Choose Best Depression Treatment
The National Institutes of Health funded study discovered that brain imaging, a technique primarily used for research, may be a new method to aid clinical decision-making.
“Our goal is to develop reliable biomarkers that match an individual patient to the treatment option most likely to be successful, while also avoiding those that will be ineffective,” explained Helen Mayberg, M.D., of Emory University, Atlanta, a grantee of the NIH’s National Institute of Mental Health.
Mayberg and colleagues report on their findings in JAMA Psychiatry.
“For the treatment of mental disorders, brain imaging remains primarily a research tool, yet these results demonstrate how it may be on the cusp of aiding in clinical decision-making,” said NIMH Director Thomas R. Insel, M.D.
Currently, physicians use trial and error to determine whether a particular patient with depression would best respond to psychotherapy or medication.
Clinicians typically try a treatment that they, or the patient, prefer for a month or two to see if it works. As a result, only about 40 percent of patients achieve remission following initial treatment.
Obviously, this practice is costly in terms of human suffering as well as health care spending.
Mayberg’s team hoped to identify a biomarker that could predict which type of treatment a patient would benefit from based on the state of his or her brain.
Using a positron emission tomography (PET) scanner, they imaged pre-treatment resting brain activity in 63 depressed patients. PET pinpoints what parts of the brain are active at any given moment by tracing the destinations of a radioactively-tagged form of glucose, the sugar that fuels its metabolism.
They compared brain circuit activity of patients who achieved remission following treatment with those who did not improve.
Activity in one specific brain area emerged as a pivotal predictor of outcomes from two standard forms of depression treatment: cognitive behavior therapy (CBT) or escitalopram (Lexapro), a serotonin specific reuptake inhibitor (SSRI) antidepressant.
If a patient’s pre-treatment resting brain activity was low in the front part of an area called the insula, on the right side of the brain, it signaled a significantly higher likelihood of remission with CBT and a poor response to escitalopram (Lexapro).
Conversely, hyperactivity in the insula predicted remission with escitalopram and a poor response to CBT.
Activity within the anterior insula of the brain best predicted whether an individual did or did not respond to a particular treatment.
The anterior insula is known to be important in regulating emotional states, self-awareness, decision-making and other thinking tasks.
Changes in insula activity have been observed in studies of various depression treatments, including medication, mindfulness training, vagal nerve stimulation and deep brain stimulation.
“If these findings are confirmed in follow-up replication studies, scans of anterior insula activity could become clinically useful to guide more effective initial treatment decisions, offering a first step towards personalized medicine measures in the treatment of major depression” said Mayberg.
The cost for a PET scan varies widely, but current estimates are from $1,000 to $4,000.
Source: National Institutes of Health
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