Antipsychotic Drugs Double Risk Of Death Among Alzheimer's Patients

New research into the effects of antipsychotic drugs commonly prescribed to Alzheimer’s patients concludes that the medication nearly doubles risk of death over three years.

The study, funded by the Alzheimer’s Research Trust, was led by Prof Clive Ballard’s King’s College London team and is published in Lancet Neurology on 9 January.

The study involved 165 Alzheimer’s patients in care homes who were being prescribed antipsychotics. 83 continued treatment and the remaining 82 had it withdrawn and were instead given oral placebos.

Findings showed a significant increase in risk of death for patients who continued taking antipsychotic medication. The difference between the two groups became more pronounced over time, with 24-month survival rates for antipsychotic-treated patients falling to 46% versus 71% on the placebo and at 36 months it was 30% versus 59%. It means that after three years, less than a third of people on antipsychotics were alive compared to nearly two thirds using the dummy drug.

Antipsychotics are used to treat symptoms of agitation, delusions and aggressive behaviour. NICE guidelines recommend that the drugs should only be used for short periods of time and where symptoms are severe, and should be very carefully monitored, although in clinical practice the average length of prescription is 1-2 years. While there is evidence of modest short-term (6-12 weeks) benefits of antipsychotic treatment for the serious behavioural symptoms of Alzheimer’s, a previous Alzheimer’s Research Trust study showed that these benefits were not evident over longer periods of treatment.

As many as 100,000 people with dementia are routinely prescribed antipsychotics in UK care homes. It could mean 23,500 people dying prematurely, according to a 2008 report by Paul Burstow MP.

Prof Clive Ballard of King’s College London said: “The results further highlight the need to seek less harmful alternatives for the long-term treatment of behavioural symptoms in Alzheimer’s patients. At the moment, there is still a limited place for antipsychotics in the treatment of Alzheimer’s, particularly severe aggression, but the serious concerns of the drugs shown by our research emphasise the urgent need to put an end to unnecessary and prolonged prescribing”.

Rebecca Wood, Chief Executive of the Alzheimer’s Research Trust, said: “The findings of this research are a real wake-up call and underline the danger of prescribing antipsychotics long-term for anything other than exceptional circumstances. We must avoid the use of these drugs as a potentially dangerous ‘chemical cosh’ to patients who would be better off without it. The study also highlights the urgent need to develop better treatments as Alzheimer’s patients have few options available to them.

"700,000 people in the UK have dementia; we urgently need to fund more research to develop the new treatments we so desperately need”.

Dr Mark Baxter of the University of Oxford added: "Antipsychotic drugs can be effective in controlling unpleasant and disturbing behavioural symptoms of Alzheimer's disease, including severe aggression, delusions, and agitation. But this study shows, conclusively, that these drugs have a severe and serious cost in terms of increased mortality. The study follows the gold-standard double-blind, placebo-controlled method for clinical trials, and is unique in examining long-term effects of antipsychotic treatment on mortality in patients with Alzheimer's disease.

"Antipsychotics do not have any effects on the underlying disease processes of Alzheimer's disease. What is needed is not only an increased application of non-drug methods to improve behavioural health in patients with dementia -- including cognitive-behavioural therapy and environmental design -- as well as a better understanding of how Alzheimer's neuropathology causes behavioural disturbances in addition to its effects on memory, so that rational drug therapies can be developed that do not have the liabilities of currently-available antipsychotics."

Olive Skins Provide Natural Defense Against Colon Cancer, Study Suggests

Researchers from the University of Granada and the University of Barcelona have shown that treatment with maslinic acid, a triterpenoid compound isolated from olive-skin pomace, results in a significant inhibition of cell proliferation and causes apoptotic death in colon-cancer cells. Maslinic acid is a novel natural compound and it is able to induce apoptosis or programmed death in human HT29 colon-cancer cells via the intrinsic mitochondrial pathway.

New research suggest this could be a useful new therapeutic strategy for the treatment of colon carcinoma.

This study is the first to investigate the precise molecular mechanisms of the anti-tumoral and pro-apoptotic effects of maslinic acid against colon-cancer. Chemopreventive agents of a natural origin, often a part of our daily diet, may provide a cheap, effective way of controlling such diseases as cancer of the colon. A wide range of studies in recent years has shown that triterpenoids hinder carcinogenesis by intervening in pathways such as carcinogen activation, DNA repair, cell cycle arrest, cell differentiation and the induction of apoptosis in cancer cells.

Triterpenoids are compounds present in a wide range of plants used in traditional medicine and known to have antitumoral properties. Low concentrations of maslinic acid are to be found in plants with medicinal properties, but its concentration in the waxy skin of olives may be as high as 80%.

The results of the study could contribute to the development of maslinic acid for use as cancer chemotherapeutic or chemopreventive agents.

Scientists See Brain Aging Before Symptoms Appear

UCLA scientists have used innovative brain-scan technology developed at UCLA, along with patient-specific information on Alzheimer's disease risk, to help diagnose brain aging, often before symptoms appear. Published in the January issue of Archives of General Psychiatry, their study may offer a more accurate method for tracking brain aging.

Researchers used positron emission tomography (PET), which allows "a window into the brain" of living people and specifically reveals plaques and tangles, the hallmarks of neurodegeneration. The PET scans were complemented by information on patients' age and congnitive status and a genetic profile.

"Combining key patient information with a brain scan may give us better predictive power in targeting those who may benefit from early interventions, as well as help test how well treatments are working," said study author Dr. Gary Small, who holds UCLA's Parlow-Solomon Chair on Aging and is a professor at the Semel Institute for Neuroscience and Human Behavior at UCLA.

Scientists took PET brain scans of 76 non-demented volunteers after they had been intravenously injected with a new chemical marker called FDDNP, which binds to plaque and tangle deposits in the brain. Researchers were then able to pinpoint where these abnormal protein deposits were accumulating.

They reported that older age correlated with higher concentrations of FDDNP in the medial and lateral temporal regions of the brain, areas involved with memory, where plaques and tangles usually collect. The average age of study volunteers was 67.

Thirty-four of the 76 volunteers carried the APOE-4 gene allele, which heightens the risk for developing Alzheimer's disease. This group demonstrated higher FDDNP levels in the frontal region of the brain, also involved in memory, than study participants without allele.

"We found that for many volunteers, the imaging scans reflected subtle brain changes, which take place before symptoms manifest," said Small, who is also director of the UCLA Center on Aging.

Small noted that the brain will try to compensate for any problems, which is why cognitive symptoms may not become apparent until much later.

"This type of scan offers an opportunity to see what is really going on in the brain," he said.

Another subset of the volunteers had mild cognitive impairment (MCI), a condition that increases the risk of developing Alzheimer's disease. These 36 volunteers had higher measures of FDDNP in the medial temporal brain regions than normal volunteers. Those who had both MCI and the APOE-4 gene had higher concentrations of FDDNP in the medial temporal brain regions than volunteers who had MCI but not APOE-4.

"We could see more advancing disease in those with mild cognitive impairment, who are already demonstrating some minimal symptoms," Small said. "Eventually, this imaging method, together with patient information like age, cognitive status and genetics, may help us better manage brain aging."

According to Small, in the future, brain aging may be controlled similarly to high cholesterol or high blood pressure. Patients would receive a brain scan and perhaps a genetic test to predict their risk. Medications and other interventions could be prescribed, if necessary, to prevent or delay future neurodegeneration, allowing doctors to protect a healthy brain before extensive damage occurs. The brain scans may also prove helpful in tracking the effectiveness of treatments.

PET, combined with the FDDNP probe, is the only imaging technology that offers a full profile of neurodegeneration that includes measures of both plaques and tangles — the physical evidence of Alzheimer's disease in the brain.

"The fact that we can see tau tangles as well as amyloid plaques is critically important in early detection of brain aging, since the tangles are the first abnormal proteins that appear in the brain, long before dementia is clinically obvious to the physician," said Dr. Jorge R. Barrio, a study author and professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA.

Such subtleties allow more insight into how the plaques and tangles spread and ultimately how Alzheimer's disease may develop.

Currently, the new FDDNP-PET scans are used in a research setting, but clinical trials are in development to bring the technology to wider patient use.

The study was funded by both government and nonprofit agencies, including the National Institutes of Health, the U.S. Department of Energy, the Ahmanson Foundation, the Larry L. Hillblom Foundation and the Tamkin Foundation.

Additional UCLA authors include Prabha Siddarth, Ph.D.; Alison C. Burggren, Ph.D.; Linda M. Ercoli, Ph.D.; Karen J. Miller, Ph.D.; Dr. Helen Lavretsky; and Susan Y. Bookheimer, Ph.D, all from the UCLA Department of Psychiatry and Biobehavioral Sciences and the Semel Institute for Neuroscience and Human Behavior at UCLA; Vladimir Kepe, Ph.D.; S.C. Huang, Ph.D.; and Michael E. Phelps, Ph.D. from the UCLA Department of Molecular and Medical Pharmacology; and Paul M. Thompson, Ph.D., and Greg M. Cole, Ph.D., from the UCLA Department of Neurology.