Sep. 25, 2013 — New research that looked at whether two commonly prescribed statin medicines, used to lower low-density lipoprotein (LDL) or 'bad cholesterol' levels in the blood, can adversely affect cognitive function has found that one of the drugs tested caused memory impairment in rats.
Between six and seven million people in the UK1 take statins daily and the findings follow anecdotal evidence of people reporting that they feel that their newly prescribed statin is affecting their memory. Last year, the US Food and Drug Administration (FDA) insisted that all manufacturers list in their side effects that statins might affect cognitive function.
The study, led by scientists at the University of Bristol and published in the journal PLOS ONE, tested pravastatin and atorvostatin (two commonly prescribed statins) in rat learning and memory models. The findings show that while no adverse cognitive effects were observed in rat performance for simple learning and memory tasks for atorvostatin, pravastatin impaired their performance.
Rats were treated daily with pravastatin (brand name -- pravachol) or atorvostatin (brand name -- Lipitor) for 18 days. The rodents were tested in a simple learning task before, during and after treatment, where they had to learn where to find a food reward. On the last day of treatment and following one week withdrawal, the rats were also tested in a task which measures their ability to recognise a previously encountered object (recognition memory).
The study's findings showed that pravastatin tended to impair learning over the last few days of treatment although this effect was fully reversed once treatment ceased. However, in the novel object discrimination task, pravastatin impaired object recognition memory. While no effects were observed for atorvostatin in either task.
The results suggest that chronic treatment with pravastatin impairs working and recognition memory in rodents. The reversibility of the effects on stopping treatment is similar to what has been observed in patients, but the lack of effect of atorvostatin suggests that some types of statin may be more likely to cause cognitive impairment than others.
Neil Marrion, Professor of Neuroscience at Bristol's School of Physiology and Pharmacology and the study's lead author, said: "This finding is novel and likely reflects both the anecdotal reports and FDA advice. What is most interesting is that it is not a feature of all statins. However, in order to better understand the relationship between statin treatment and cognitive function, further studies are needed."
Sep. 23, 2013 — Protecting the stem cells that reside in and around the hippocampus -- a C-shaped area in the temporal lobe on both sides of the brain associated with the ability to form and store memories -- substantially reduces the rate of cancer patients' memory loss during whole-brain radiotherapy without a significant risk of recurrence in that area of the brain, a new study shows. Results of the Phase II clinical trial of patients with brain metastases are being presented today at the American Society for Radiation Oncology (ASTRO) annual meeting.
"Memory loss, especially short-term recall, is an important consideration for patients receiving whole-brain radiotherapy," says the study's co-principal investigator, Minesh P. Mehta, M.B., Ch.B., professor of radiation oncology at the University of Maryland School of Medicine. "We found that reducing the radiation dose to the stem-cell niches surrounding the hippocampus during treatment was clearly associated with memory preservation without an inordinate risk of relapse in that portion of the brain. The findings far exceeded our expectations."
Based on previous research, the predicted rate of cognitive decline at four months for patients receiving whole-brain radiation for brain metastases was 30 percent. Researchers designed the clinical trial so that a positive result would be a rate reduced by half, to 15 percent. The observed rate in the trial was actually 7 percent -- significantly better than the baseline rate of 30 percent. With a third fewer patients to evaluate, the rate of decline observed at six months was 2 percent, although comparable data from the historic control study were not available.
"These Phase II results, while not absolutely conclusive, offer very important insights which we hope to validate in a larger, randomized Phase III clinical trial," says Dr. Mehta, a radiation oncologist at the University of Maryland Marlene and Stewart Greenebaum Cancer Center who chairs the Radiation Therapy Oncology Group (RTOG) brain tumor committee. The RTOG, which managed the Phase II trial, also plans to manage the Phase III Study.
Co-principal investigator Vinai Gondi, M.D., will present the findings at the plenary session at the ASTRO annual meeting in Atlanta. He practices at Central DuPage Hospital Cancer Center in Warrenville, Ill.
E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and Dean of the University of Maryland School of Medicine, says, "Preserving neurocognitive function is extremely important in treating patients with brain metastases, and the results of this latest study on hippocampal-avoidance radiotherapy led by Dr. Mehta are very encouraging. This technique, if validated in a randomized clinical trial, will give physicians a significant new tool to help maintain patients' quality of life while aggressively treating their cancer."
Patients in the study, the majority of them with lung cancer that had spread to the brain, were treated with intensity-modulated radiation therapy (IMRT), which enabled doctors to shape the radiation beams to avoid the hippocampus. Researchers used a standardized cognitive function assessment -- the Hopkins Verbal Learning Test (HVLT) -- to measure patients' baseline memory, such as their ability to recall information immediately or after a delay, with follow-up at two, four and six months.
A total of 113 patients were recruited between 2011 and 2013; investigators were able to evaluate 42 patients at four months and 29 patients at six months. The median survival for the participants was 6.8 months. Three patients (4.5 percent) experienced progression of their disease in the hippocampal region, which was within the expected range.
Dr. Mehta says that the radiation affects cognitive function by damaging nerve cells as well as stem cells, which help to regenerate nerve cells that support memory formation. "These stem-cell niches are exquisitely sensitive to radiation and are involved in neurogenesis -- the process of generating new neurons, or nerve cells. Although we call it hippocampal-avoidance radiotherapy, we really are targeting the stem-cell niches in and around the hippocampus," Dr. Mehta says.
He notes that factors other than radiation may also contribute to cognitive decline in patients with brain metastases, including medicines to control seizures or swelling in the brain. The cancer itself may also have an effect.
Sep. 18, 2013 — The loss of estrogens at menopause increases a woman's risk of dementia and Alzheimer's disease, yet hormone replacement therapy can cause harmful side effects.
Knowing the exact mechanism of estrogen activation in the brain could lead to new targets for drug development that would provide middle-aged women the cognitive benefits of hormone replacement therapy without increasing their risk for cardiovascular disease or breast cancer.
In a new study, Karyn Frick, professor of psychology at the University of Wisconsin-Milwaukee (UWM), uncovers details about estrogen's role in the complex cellular communication system underlying memory formation.
"The receptor mechanisms that regulate estrogen's ability to enhance memory are still poorly understood," says Frick. "With this study, we've begun to sort out several of the key players needed for estrogens to mediate memory formation."
The research, published in the the Journal of Neuroscience today, focused on estrogen effects in a brain region called the hippocampus, which deteriorates with age or Alzheimer's disease. The researchers found that each of the two known estrogen receptors rapidly activate a specific cellular pathway necessary for memory formation in the hippocampus of female mice, but only if they interact with a certain glutamate receptor, called mGluR1.
The study revealed that when this glutamate receptor is blocked, the cell-signaling protein ERK cannot be activated by the potent estrogen, 17β-estradiol. Because ERK activation is necessary for memory formation, estradiol failed to enhance memory among mice in which mGluR1 was blocked.
Frick's team also found evidence that estrogen receptors and mGluR1 physically interact at the cell membrane, allowing estradiol to influence memory formation within seconds to minutes. Collectively, the data provide the first evidence that the rapid signaling initiated by such interactions is essential for estradiol to enhance memory regulated by the hippocampus.
"Our data suggesting that interactions between estrogen receptors and mGluR1 at the cell membrane are critical for estradiol to enhance memory provides important new information about how estrogens regulate memory formation," Frick says.
"Because membrane proteins are better targets for drug development than proteins inside the cell, these data could lead to a new generation of therapies that provide the cognitive benefits of estrogens without harmful side effects."
Sep. 17, 2013 — Heart patients' mental state and thinking abilities may help predict whether costly and potentially dangerous early hospital readmission will follow their release after treatment, according to the results of a significant new study by Henry Ford Hospital researchers.
The findings have important implications for the health care industry as it struggles to contain unnecessary costs, according to the study's lead author, Mark W. Ketterer, Ph.D., a psychologist and administrator for Henry Ford.
The study is published online in Psychosomatics.
"Wasted resources have become a central concern in American health care, including readmission soon after a patient has been released from hospital care," Dr. Ketterer says.
"Because heart failure has one of the highest readmission rates of all conditions that have been studied in Medicare and Medicaid populations, we decided to focus on it and try to identify predictors for early readmission."
What was found, Ketterer explains, was that a psychiatric history of depression, anxiety and other mood disorders, as well as impairments in a patient's ability to think, remember and reason, may well be such predictors.
"Given both the exorbitant fiscal costs and known health risks of hospitalization, including exposure to drug-resistant infections and medical errors, it could be well worth further study to test our findings." he adds.
Currently, Medicare is penalizing hospitals for what it considers excessive readmission rates. Last month, Medicare said it will access $227 million in fines against hospitals in 49 states as part of an initiative to reduce the number of patients readmitted within a month. Medicare said that 2,225 hospitals will see payments reduced for a year. Henry Ford Hospital is one of hospitals that will see a reduction in payments starting Oct. 1.
In the study, the researchers chose 84 patients who were admitted to Henry Ford Hospital for treatment of acute congestive heart failure. Each was interviewed for basic clinical and demographic information and asked to complete several questionnaires measuring depression, anxiety and spirituality.
Their medical risk factors -- including other illnesses and their severity -- and behavioral risk factors -- including depression and such cognitive impairments as loss of reasoning, planning, forgetfulness and other reduced mental functions -- as well as admissions during the past year and readmissions during the previous 30 days were recorded.
The patient group was 62 percent male with an average age of 66. Central nervous system disorders -- including Alzheimer's, dementia, closed-head injury and others -- were present in 21 percent. Nearly 70 percent lived with a family member, 24 percent acknowledged a psychiatric history, 36 percent used or had used antidepressants, 40 percent had coronary artery disease, 43 percent had diabetes, 86 percent had hypertension, 20 percent had chronic obstructive pulmonary disease, 48 percent had chronic kidney disease and 24 percent were alcohol or drug abusers.
The researchers found that depression, a history of substance abuse, and a history of coronary artery disease were related to hospital admissions during the previous year. Factors in 30-day readmission rates included immediate memory problems and a history of psychiatric treatment and/or the use of an antidepressant. The severity of congestive heart failure, however, was not a factor in either admission or readmission rates.
"Our results agree with several recent studies in finding an adverse impact of depression on admission and readmission rates," Ketterer says. "In addition, substance abuse and chronic kidney disease may also adversely impact these rates in congestive heart failure patients.
"Even severe heart disease, except in the extreme, appears to be manageable after release from the hospital unless it's complicated by one or more of the behavioral factors."
But perhaps most important in these findings is the relationship between emotional stress and/or cognitive impairment and early readmission to the hospital. "Both suggest a possible way to predict readmission and avoid it," Ketterer says.
Educating patients about their mental illness, as well as involving live-in family members in helping with the patient's medications, and keeping medical appointments may also help reduce hospital readmissions, the study concluded.