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All antipsychotic drugs can increase the risk of stroke, but the risk is greatest among older patients with dementia, British researchers report.

Concerns about the risk of stroke and antipsychotics were first raised in 2002, especially in people with dementia. In 2004, Britain’s Committee on Safety of Medicines recommended that antipsychotics not be used in people with dementia. And, in 2005, the U.S. Food and Drug Administration ordered manufacturers of atypical antipsychotics to add a black box warning to their products about the increased risk for stroke.

“Antipsychotics are effective in treating potentially very distressing psychiatric symptoms, but as with all drugs, their use can be associated with a range of benefits and possible side effects,” said study author Dr. Ian Douglas, a research fellow at the London School of Hygiene and Tropical Medicine. “This study has further clarified the potential for antipsychotics to increase the risk of stroke.”

Both typical (first generation) and atypical (second generation) antipsychotics are associated with an increased risk of stroke, Douglas said. “This risk is substantially higher in patients with dementia than those without. These findings need to be factored into prescribing decisions made by doctors caring for patients with often-distressing and difficult-to-treat psychiatric symptoms.”

For the study, Douglas and his colleague Liam Smeeth, a professor of clinical epidemiology, collected data on 6,790 patients who had suffered a stroke and were taking antipsychotic drugs. Patients taking antipsychotic drugs were 1.7 times more likely to have a stroke, and patients with dementia taking antipsychotics were 3.5 times more likely to have a stroke.

The risk for stroke was slightly higher for people taking the newer atypical antipsychotics, compared with people taking the older typical antipsychotics. Atypical antipsychotics include drugs such as Abilify, Clozaril and Zyprexa. Typical antipsychotics include Thorazine, Haldol and Clopixol.

The study authors did not look at the potential mechanisms associated with antipsychotics that cause stroke, or why the risk appears higher with atypical antipsychotics.

“We believe that the risks associated with antipsychotic use in patients with dementia generally outweigh the potential benefits, and, in this patient group, use of antipsychotic drugs should be avoided wherever possible,” Douglas said. “For other patients, careful consideration must be given to the likely individual risks and benefits of any prescribing decision.”

The findings were published online Aug. 29 in the British Medical Journal.

Dr. Sam Gandy is associate director of the Alzheimer’s Disease Research Center at Mount Sinai Medical Center in New York City, and chairman of the Alzheimer’s Association’s national medical and scientific advisory council. He said the new study addresses an “important topic and elevates the concern about risks of antipsychotics to a whole new level. The FDA [U.S. Food and Drug Administration] might investigate whether availability limitations or warning labeling should be imposed.

Scientists for the first time have peered into people’s brains to directly measure the ebb and flow of a substance notorious for its role in Alzheimer’s disease.

The delicate research was performed not with Alzheimer’s patients but with people suffering severe brain injuries — because a brain injury increases the risk of developing dementia later in life.

The goal is to learn why, so that doctors one day might be able to lower that risk.

But with this first-step study, a team of scientists from Missouri and Italy got a surprise.

Too much of that Alzheimer’s-related protein, called beta-amyloid, is thought to be harmful. So the team had expected beta-amyloid levels to spike right after the injury and then drop as patients recovered.

Instead, beta-amyloid levels increased as patients improved and dropped if they got worse, lead researcher Dr. David Brody, a neurologist at Washington University in St. Louis, reported Friday in the journal Science.

What’s going on? Beta-amyloid seems to be a marker of increased brain activity as patients improved.

If so, what started as a study of Alzheimer’s risk might have implications for how the brain-injured are tracked in intensive-care units — although that will take much more research to prove.

“Our study is just the beginning,” Brody said. “Amyloid-beta measurements in the brain may turn out to be a good indicator of how well the cells are communicating with each other.’

Beta-amyloid is best known as the sticky goo that makes up the hallmark plaques inside the brains of Alzheimer’s victims. But it doesn’t start out as gunk. Soluble forms are found in the fluid that bathes the brain, although scientists don’t understand its purpose, or just what happens to trigger formation of those bad plaques.

Nor do they understand how brain trauma so often leads to later Alzheimer’s. One possibility is that extra beta-amyloid speeds whatever dementia-forming process might be lurking among brain cells. Another theory is that the injury decreases a person’s “cognitive reserve,” so that symptoms merely become apparent sooner.

Brody thought brain-injured patients could offer a precious opportunity to start testing that first possibility. These patients were undergoing brain surgery anyway. What if surgeons could insert an extra tiny tube at the same time that would allow hour-to-hour sampling of brain fluid, to measure beta-amyloid?

It’s a technique called intracerebral microdialysis, and colleagues at Washington University already had performed it in mice — linking increased synaptic activity, or communication between brain cells, to increased beta-amyloid.

Brody teamed with Dr. Sandra Magnoni of the Ospedale Maggiore Policlinico, a major trauma center in Milan that has experience with the technique. They asked the families of patients suffering brain injuries from car crashes, falls or hemorrhages from burst blood vessels if they’d agree to the experiment. Eighteen said yes.

Roughly 24 hours after the initial injury, the catheter was placed in patients’ brains, where it stayed for three to seven days. ICU doctors and nurses otherwise provided routine care, tracking patients’ neurologic changes with a standard tool called the Glasgow Coma Score.

Brody tracked the beta-amyloid levels and found they mirrored that coma score, with a direct relationship to each patient’s neurological status.

That means the findings agreed with the previous research on mice. That’s important, as so much Alzheimer’s research must be performed in animals, said Dr. Ramona Hicks, a specialist in traumatic brain injury at the National Institutes of Health, which helped fund the work.

Brody cautions that beta-amyloid might have spiked in everyone right at the time of injury, something his study started too late to measure.

Also, it only measured total beta-amyloid levels, not a strung-together form that’s thought to be toxic to cells, something Brody hopes to try next.

While the work raises more questions than it answers, it brings researchers a valuable new tool for studying both Alzheimer’s risk and just what happens during brain-injury recovery.

“It sort of sets a platform for future studies,” said NIH’s Hicks.

Talk about an extreme makeover: Scientists have transformed one type of cell into another in living mice, a big step toward the goal of growing replacement tissues to treat a variety of diseases.

The cell identity switch turned ordinary pancreas cells into the rarer type that churns out insulin, essential for preventing diabetes. But its implications go beyond diabetes to a host of possibilities, scientists said.

It’s the second advance in about a year that suggests that someday doctors might be able to use a patient’s own cells to treat disease or injury without turning to stem cells taken from embryos.

The work is “a major leap” in reprogramming cells from one kind to another, said one expert not involved in the research, John Gearhart of the University of Pennsylvania.

That’s because the feat was performed in living mice rather than a lab dish, the process was efficient and it was achieved directly without going through a middleman like embryonic stem cells, he said.

The newly created cells made insulin in diabetic mice, though they were not cured. But if the experiment’s approach proves viable, it might lead to treatments like growing new heart cells after a heart attack or nerve cells to treat disorders like ALS, formerly Lou Gehrig’s disease.

Douglas Melton, co-director of the Harvard Stem Cell Institute and a researcher with the Howard Hughes Medical Institute, cautioned that the approach is not ready for people.

He and his colleagues report the research in a paper published online Wednesday by the journal Nature.

Basically, the identity switch comes about by a reprogramming process that changes the pattern of which genes are active and which are shut off.

Scientists have long hoped to find a way to reprogram a patient’s cells to produce new ones. Research with stem cells, and similar entities called iPS cells that were announced last year, has aimed to achieve this in a two-step process.

The first step results in a primitive and highly versatile cell. This intermediary is then guided to mature into whatever cell type scientists want. That guiding process has proven difficult to do efficiently, especially for creating insulin-producing cells, Gearhart noted.

In contrast, the new method holds the promise of going directly from one mature cell type to another. It’s like a scientist becoming a lawyer without having to go back to kindergarten and grow up again, Melton says.

So, he says, someday scientists may be able to replace dead nerve or heart cells in people by converting some neighboring cells. At the same time, he stressed that it’s still important to study embryonic stem cells and iPS cells.

The Melton team started its work with pancreas cells that pump out gut enzymes used in digestion and turned them into pancreatic “beta” cells, which make insulin.

The researchers destroyed beta cells in mice with a poison, giving the mice diabetes. Then they injected the pancreas with viruses that slipped into the enzyme-making cells. These viruses delivered three genes that control the activity of other genes.

Just three days later, new insulin-secreting cells started to show up. By a week after that, more than a fifth of the virally infected cells started making insulin. That shows “an amazingly efficient effect,” commented Richard Insel, executive vice president of research at the Juvenile Diabetes Research Foundation.

Scientists found evidence that the newcomers were converts from mature enzyme-making cells. They identified the new cells as beta cells by their detailed appearance and behavior, and Melton said they’ve continued functioning for months.

The new cells didn’t fully replenish the insulin supply, but maybe there were too few of them, or they were hampered by not forming clusters like ordinary beta cells do, researchers said.

The work brings “more excitement to the idea of using reprogramming as a way to treat diabetes,” said researcher Mark Kay of Stanford University, who is studying the approach with liver cells.

Christopher Newgard, who studies beta cells at Duke University Medical Center, called the work convincing but cautioned that significant scientific questions remained about using the approach in treating disease.

Melton, who began his diabetes research in 1993 when his infant son was diagnosed with the illness, said he’s obsessed with trying to find a new treatment or cure for Type 1 diabetes, in which beta cells are destroyed.

“I wake up every day thinking about how to make beta cells,” he said.

Melton said he hopes drugs can replace the virus approach because of concern about injecting viruses into people.

As for converting other kinds of cells, scientists noted that the two cell types in the mouse experiment are closely related, and it remains to be shown whether the trick can be achieved with more distant combinations. In any case, scientists would have to deliver different reprogramming signals to other kinds of cells, Melton said.