Basic computing elements created in bacteria

Researchers unveil a series of sensors, memory switches, and circuits that can be encoded in the common human gut bacterium. These basic computing elements will allow the bacteria to sense, memorize, and respond to signals in the gut, with future applications that might include the early detection and treatment of inflammatory bowel disease or colon cancer, they say.

The illustration depicts Bacteroides thetaiotaomicron (white) living on mammalian cells in the gut (large pink cells coated in microvilli) and being activated by exogenously added chemical signals (small green dots) to express specific genes, such as those encoding light-generating luciferase proteins (glowing bacteria).

Credit: Janet Iwasa

The "friendly" bacteria inside our digestive systems are being given an upgrade, which may one day allow them to be programmed to detect and ultimately treat diseases such as colon cancer and immune disorders.

In a paper published in the journal Cell Systems, researchers at MIT unveil a series of sensors, memory switches, and circuits that can be encoded in the common human gut bacterium Bacteroides thetaiotaomicron.

These basic computing elements will allow the bacteria to sense, memorize, and respond to signals in the gut, with future applications that might include the early detection and treatment of inflammatory bowel disease or colon cancer.

Researchers have previously built genetic circuits inside model organisms such as E. coli. However, such strains are only found at low levels within the human gut, according to Timothy Lu, an associate professor of biological engineering and of electrical engineering and computer science, who led the research alongside Christopher Voigt, a professor of biological engineering at MIT.

"We wanted to work with strains like B. thetaiotaomicron that are present in many people in abundant levels, and can stably colonize the gut for long periods of time," Lu says.

The team developed a series of genetic parts that can be used to precisely program gene expression within the bacteria. "Using these parts, we built four sensors that can be encoded in the bacterium's DNA that respond to a signal to switch genes on and off inside B. thetaiotaomicron," Voigt says.

These can be food additives, including sugars, which allow the bacteria to be controlled by the food that is eaten by the host, Voigt adds.

Bacterial "memory"

To sense and report on pathologies in the gut, including signs of bleeding or inflammation, the bacteria will need to remember this information and report it externally. To enable them to do this, the researchers equipped B. thetaiotaomicron with a form of genetic memory. They used a class of proteins known as recombinases, which can record information into bacterial DNA by recognizing specific DNA addresses and inverting their direction.

The researchers also implemented a technology known as CRISPR interference, which can be used to control which genes are turned on or off in the bacterium. The researchers used it to modulate the ability of B. thetaiotaomicron to consume a specific nutrient and to resist being killed by an antimicrobial molecule.

The researchers demonstrated that their set of genetic tools and switches functioned within B. thetaiotaomicron colonizing the gut of mice. When the mice were fed food containing the right ingredients, they showed that the bacteria could remember what the mice ate.

Expanded toolkit

The researchers now plan to expand the application of their tools to different species of Bacteroides. That is because the microbial makeup of the gut varies from person to person, meaning that a particular species might be the dominant bacteria in one patient, but not in others.

"We aim to expand our genetic toolkit to a wide range of bacteria that are important commensal organisms in the human gut," Lu says.

The concept of using microbes to sense and respond to signs of disease could also be used elsewhere in the body, he adds.

In addition, more advanced genetic computing circuits could be built upon this genetic toolkit in Bacteroides to enhance their performance as noninvasive diagnostics and therapeutics.

"For example, we want to have high sensitivity and specificity when diagnosing disease with engineered bacteria," Lu says. "To achieve this, we could engineer bacteria to detect multiple biomarkers, and only trigger a response when they are all present."

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The above post is reprinted from materials provided by Massachusetts Institute of Technology.

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Scientists separate medical benefits of cannabis from 'unwanted' side effects

Scientists have found a way to separate medical benefits of cannabis from its unwanted side effects. The research was carried out in mice, but it is hoped that the breakthrough will pave the way for safe cannabis-based therapies that do not cause alterations in mood, perception or memory. Last year the team discovered how the main psychoactive ingredient in cannabis, known as THC, reduces tumor growth in cancer patients.

These findings reveal how the cognitive effects of THC are triggered by a pathway which is separate from some of its other effects.

Credit: © William Casey / Fotolia

Scientists at the University of East Anglia in collaboration with the University Pompeu Fabra in Barcelona have found a way to separate the medical benefits of cannabis from its unwanted side effects.

The research comes from the team that discovered how the main psychoactive ingredient in cannabis, known as THC, reduces tumour growth in cancer patients.

Their latest findings, published today in the journal PLOS Biology, reveal how the cognitive effects of THC are triggered by a pathway which is separate from some of its other effects.

That pathway involves both a cannabinoid receptor and a serotonin receptor. When it is blocked, THC can still exert several beneficial effects -- including pain relief -- while avoiding impairment of memory.

The research was carried out in mice, but it is hoped that the breakthrough will pave the way for safe cannabis-based therapies that do not cause alterations in mood, perception or memory.

Dr Peter McCormick, from UEA's school of Pharmacy, said: "THC, the major active component of marijuana, has broad medical use -- including for pain relief, nausea and anxiety. Our previous research has also found that it could reduce tumour size in cancer patients. However it is also known to induce numerous undesirable side effects such as memory impairment, anxiety and dependence.

"There has been a great deal of medical interest in understanding the molecular mechanisms at work in THC, so that the beneficial effects can be harnessed without the side-effects.

"THC acts through a family of cell receptors called cannabinoid receptors. Our previous research revealed which of these receptors are responsible for the anti-tumour effects of THC. This new research demonstrates how some of the drug's beneficial effects can be separated from its unwanted side effects."

The research team carried out behavioural studies in mice and investigated how pathways in their brains operate under THC. They found that the absence of a particular serotonin receptor (5HT2AR) reduced some of the effects of THC -- such as its amnesic effect, based on a standard memory test. But treatment to reduce 5HT2AR did not change other effects of THC, including pain relief.

"This research is important because it identifies a way to reduce some of what, in medical treatment, are usually thought of as THC's unwanted side effects, while maintaining several important benefits including pain reduction."

But Dr McCormick added that patients should not be tempted to self-medicate.

"Patients should not use cannabis to self-medicate, but I hope that our research will lead to a safe synthetic equivalent being available in the future."

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The above post is reprinted from materials provided by University of East Anglia.

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Rhythm of cells: Daily changes in human cells

Life is subject to natural rhythms, such as the light and dark cycle or seasonal variation in temperature. A recent study shows that the composition of human cell membranes varies depending on the time of day. These cyclical changes in cell membranes could have a significant impact on health and disease, scientists say.

The analysis of cell membranes revealed significant daily rhythms in eleven fatty acids.

Credit: © magann / Fotolia

Life is subject to natural rhythms, such as the light and dark cycle or seasonal variation in temperature. A recent study by researchers at the Vetmeduni Vienna, shows that the composition of human cell membranes varies depending on the time of day. These cyclical changes in cell membranes could have a significant impact on health and disease. The results were published in the Journal of Biological Rhythms.

Fatty acids are important components of cell membranes. They have signalling functions within the cells and play a role in controlling metabolic processes in the entire body. Thomas Ruf and Walter Arnold of the Research Institute of Wildlife Ecology at the University of Veterinary Medicine, Vienna, investigated these cyclic fluctuations in human cells.

"Nearly all physiological processes in humans and animals, such as body temperature or heart rate, undergo daily rhythms, and many even exhibit annual fluctuations. We wanted to find out if these rhythms are related to changes in cell membranes," explains first author Thomas Ruf.

The researchers investigated buccal mucosa cells in 20 subjects over a period of one year. Study participants collected their cells on a predetermined day every month at three hour intervals by intensively rinsing their mouths with water and then freezing the samples in special flasks.

The composition of fatty acids changes during the course of the day

The analysis of the cell membranes revealed significant daily rhythms in eleven fatty acids. Several fatty acids were present in higher concentrations at night, others during the daytime. "The cellular changes have one thing in common: they always occurred at about the same time in all participants. This shows that a clear rhythm is present," Ruf explains.

"From animal physiology, we know that the fatty acid composition in cell membranes can be remodelled in response to environmental conditions. Fatty acid composition is especially subject to seasonal fluctuations. However, while the participants of our study all showed daily fluctuations, seasonal changes occurred only in individual cases."

In contrast to wildlife, no clear annual rhythm could be seen in the fatty acid patterns of the study participants. Around one half of the subjects showed yearly rhythms, but these were not synchronous. Some participants exhibited a peak in spring or in summer, while in others the same fatty acid had higher concentrations in autumn or in the winter. "In western countries, seasons are having an increasingly smaller impact on the body. This is due to the prevalence of artificial light, which makes for longer days, and the long heating season, which minimises temperature fluctuations. Annual rhythms still exist, but these are no longer synchronised with the seasons," says Ruf.

Certain diseases occur in seasonal rhythms

This remodelling of human cell membranes could be of medical importance. It is known that certain fatty acids such as omega-3 fatty acids offer protection against certain diseases, while others, if taken up in excess, can have negative effects. The composition of the fatty acids in cell membranes may therefore have a variety of different health consequences.

"This may also explain why certain diseases and even death occur at specific times of day. Statistically speaking, heart attacks occur more often in the morning than in the evening. Blood pressure usually rises before noon. We currently do not know exactly what causes the changes in the composition of the cell membranes. The type of food eaten and the time of food intake may also play a role. These questions must still be researched," Ruf points out.

In addition to consuming sufficient quantities of important healthy fatty acids such as omega-3 fatty acids in fish oil or oleic acids in olive oil, it may also be important to choose the right time for intake.

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The above post is reprinted from materials provided by University of Veterinary Medicine Vienna.

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Cell structure discovery advances understanding of cancer development

A cell structure has been discovered that could help scientists understand why some cancers develop. For the first time, a structure called 'the mesh' has been identified which helps to hold together cells. This discovery changes our understanding of the cell's internal scaffolding.

A 3-D view of the mesh: microtubules (green tubes) of the mitotic spindle are held together by a yellow network, the mesh.

Credit: Warwick Medical School

University of Warwick researchers have discovered a cell structure which could help scientists understand why some cancers develop.

For the first time a structure called 'the mesh' has been identified which helps to hold together cells. This discovery, which has been published in the online journal eLife, changes our understanding of the cell's internal scaffolding.

This also has implications for researchers' understanding of cancer cells as the mesh is partly made of a protein which is found to change in certain cancers, such as those of the breast and bladder.

The finding was made by a team led by Dr Stephen Royle, associate professor and senior Cancer Research UK Fellow at the division of biomedical cell biology at Warwick Medical School. Dr Royle said: "As a cell biologist you dream of finding a new structure in cells but it's so unlikely. Scientists have been looking at cells since the 17th Century and so to find something that no-one has seen before is amazing."

Researchers at the University's Warwick Medical School made the discovery by accident while looking at gaps between microtubules which are part of the cells' 'internal skeleton'. In dividing cells, these gaps are incredibly small at just 25 nanometres wide -- 3,000 times thinner than a human hair.

One of Dr Royle's PhD students was examining structures called mitotic spindles in dividing cells using a technique called tomography which is like a hospital CAT scan but on a much smaller scale. This meant that they could see the structure which they later named the mesh.

Mitotic spindles are the cell's way of making sure that when they divide each new cell has a complete genome. Mitotic spindles are made of microtubules and the mesh holds the microtubules together, providing support. While "inter-microtubule bridges" in the mitotic spindle had been seen before, the researchers were the first to view the mesh.

The study received funding and support from Cancer Research UK and North West Cancer Research.

Dr Royle said: "We had been looking in 2D and this gave the impression that 'bridges' linked microtubules together. This had been known since the 1970s. All of a sudden, tilting the fibre in 3D showed us that the bridges were not single struts at all but a web-like structure linking all the microtubules together."

The discovery impacts on the research into cancerous cells. A cell needs to share chromosomes accurately when it divides otherwise the two new cells can end up with the wrong number of chromosomes. This is called aneuploidy and this has been linked to a range of tumours in different body organs.

The mitotic spindle is responsible for sharing the chromosomes and the researchers at the University believe that the mesh is needed to give structural support. Too little support from the mesh and the spindle will be too weak to work properly, however too much support will result in it being unable to correct mistakes. It was found that one of the proteins that make up the mesh, TACC3, is over-produced in certain cancers. When this situation was mimicked in the lab, the mesh and microtubules were altered and cells had trouble sharing chromosomes during division.

Dr Emma Smith, senior science communications officer at Cancer Research UK, said: "Problems in cell division are common in cancer -- cells frequently end up with the wrong number of chromosomes. This early research provides the first glimpse of a structure that helps share out a cell's chromosomes correctly when it divides, and it might be a crucial insight into why this process becomes faulty in cancer and whether drugs could be developed to stop it from happening."

North West Cancer Research (NWCR) has funded the research as part of a collaborative project between the University of Warwick and the University of Liverpool, where part of the research is being carried out.

Anne Jackson, CEO at NWCR, said: "Dr Royle and Professor Ian Prior at the University of Liverpool have made significant inroads into our understanding of the way in which cancer cells behave, which could potentially better inform future cancer therapies.

"As a charity we fund only the highest standard of research, as evidenced by Dr Royle's work.

"All our funded projects undergo a thorough peer review process, before they are considered by our scientific committee. Our specially selected scientific committee includes some of the UK's leading professors, award-winning scientists and pioneering professionals."

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The above post is reprinted from materials provided by University of Warwick

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Surprising Health Benefits of Sex

Sexual Health

"When you're in the mood, it's a sure bet that the last thing on your mind is boosting your immune system or maintaining a healthy weight. Yet good sex offers those health benefits and more. That's a surprise to many people, says Joy Davidson, PhD, a New York psychologist and sex therapist. 'Of course, sex is everywhere in the media,' she says. 'But the idea that we are vital, sexual creatures is still looked at in some cases with disgust or in other cases a bit of embarrassment. So to really take a look at how our sexuality adds to our life and enhances our life and our health, both physical and psychological, is eye-opening for many people.'

Sex does a body good in a number of ways, according to Davidson and other experts. The benefits aren't just anecdotal or hearsay -- each of these health benefits of sex is backed by scientific scrutiny." *

Sex Relieves Stress

"A big health benefit of sex is lower blood pressure and overall stress reduction, according to researchers from Scotland who reported their findings in the journal Biological Psychology. They studied 24 women and 22 men who kept records of their sexual activity. Then the researchers subjected them to stressful situations -- such as speaking in public and doing verbal arithmetic -- and noted their blood pressure response to stress. Those who had intercourse had better responses to stress than those who engaged in other sexual behaviors or abstained."

Sex Lowers Blood Pressure

"Another study published in Biological Psychology found that frequent intercourse was associated with lower diastolic blood pressure (the lower, or second, number in a blood pressure reading). This study focused on people living with their sex partner.

Still further research found a link between partner hugs and lower blood pressure in women.

Elevated blood pressure is a risk factor for coronary artery disease, heart attack, kidney disease, and stroke."

Sex Boosts Immunity

"Good sexual health may mean better physical health. Having sex once or twice a week has been linked with higher levels of an antibody called immunoglobulin A or IgA, which can protect you from getting colds and other infections. Scientists at Wilkes University in Wilkes-Barre, Pa., took samples of saliva, which contain IgA, from 112 college students who reported the frequency of sex they had.

Those in the 'frequent' group -- once or twice a week -- had higher levels of IgA than those in the other three groups -- who reported being abstinent, having sex less than once a week, or having it very often, three or more times weekly."

Sex Counts As Exercise

"'Sex is a great mode of exercise,' says Patti Britton, PhD, a Los Angeles sexologist and president of the American Association of Sexuality Educators and Therapists. It takes work, from both a physical and psychological perspective, to do it well, she says.

The benefits of sex as a form of exercise are many - sex can improve your cardiovascular fitness, strength, flexibility, and balance, not to mention your emotional health."

Sex Burns Calories

"Thirty minutes of sex burns 85 calories or more. It may not sound like much, but it adds up: 42 half-hour sessions will burn 3,570 calories, more than enough to lose a pound. The number of calories burned during sex is about the same as the number burned by walking at 2 miles per hour.

Doubling up on the 30 minute sessions, you could drop that pound in 21 hour-long sessions."

Sex Improves Cardiovascular Health

"While some older folks may worry that the efforts expended during sex could cause a stroke, that's not so, according to researchers from England. In a study published in theJournal of Epidemiology and Community Health, scientists found that the frequency of sex was not associated with stroke in the 914 men they followed for 20 years.

And the heart health benefits of sex don't end there. The researchers also found that having sex twice or more a week reduced the risk of fatal heart attack by half for the men, compared with those who had sex less than once a month."

Sex Boosts Self-Esteem

"Boosting self-esteem was one of 237 reasons people have sex, collected by University of Texas researchers and published in the Archives of Sexual Behavior.

That finding makes sense to Gina Ogden, PhD, a sex therapist and marriage and family therapist in Cambridge, Mass., although she finds that those who already have self-esteem say they sometimes have sex to feel even better. 'One of the reasons people say they have sex is to feel good about themselves,' she tells WebMD. 'Great sex begins with self-esteem, and it raises it. If the sex is loving, connected, and what you want, it raises it.'"

Sex Strengthens Your Well-Being

"Sex, like any activity that fosters a close and loving connection to your partner, not only raises self-esteem, but strengthens your overall sense of well-being. Studies have shown that people with strong social support networks (which includes lovers) are healthier and happier than their less-connected peers." 

Sex Improves Intimacy

"Having sex and orgasms increases levels of the hormone oxytocin, the so-called love hormone, which helps us bond and build trust. Researchers from the University of Pittsburgh and the University of North Carolina evaluated 59 premenopausal women before and after warm contact with their husbands and partners ending with hugs. They found that the more contact, the higher the oxytocin levels.

'Oxytocin allows us to feel the urge to nurture and to bond,' Britton says.

Higher oxytocin has also been linked with a feeling of generosity. So if you're feeling suddenly more generous toward your partner than usual, credit the love hormone." 

Sex Reduces Pain

"As the hormone oxytocin surges, endorphins increase, and pain declines. So if your headache, arthritis pain, or PMS symptoms seem to improve after sex, you can thank those higher oxytocin levels.

Oxytocin – The Love Hormone

"A study published in the Bulletin of Experimental Biology and Medicine examined the response of the 'love hormone' oxytocin on pain perception in an experiment with 48 volunteers. Study participants inhaled oxytocin vapor and then had their fingers pricked. Those who had inhaled oxytocin lowered their pain threshold by more than half."

Sex Reduces Prostate Cancer Risk

"Frequent ejaculations, especially in 20-something men, may reduce the risk of prostate cancer later in life, Australian researchers reported in the British Journal of Urology International. When they followed men diagnosed with prostate cancer and those without, they found no association of prostate cancer with the number of sexual partners as the men reached their 30s, 40s, and 50s.

But they found men who had five or more ejaculations weekly while in their 20s reduced their risk of getting prostate cancer later by a third.

Another study, reported in the Journal of the American Medical Association, found that frequent ejaculations, 21 or more a month, were linked to lower prostate cancer risk in older men, as well, compared with less frequent ejaculations of four to seven monthly."

Sex Strengthens Pelvic Floor Muscles

"For women, doing a few pelvic floor muscle exercises known as Kegel exercises during sex offers a couple of benefits. You will enjoy more pleasure, and you'll also strengthen the area and help to minimize the risk of incontinence later in life.

To do a basic Kegel exercise, tighten the muscles of your pelvic floor, as if you're trying to stop the flow of urine. Count to three, then release."

Additional Benefits of Kegel Exercises

"Kegel exercises have a number of proven health benefits in addition to making sex more enjoyable. The strengthening of the pelvic floor muscles can help prevent prolapse (a slipping out of position) of the vagina, uterus, and bladder. Pelvic floor muscles may be weakened later in life as a result of childbearing, being overweight, and aging. Kegel exercises help offset the consequences of weakened pelvic floor muscles."

Sex Helps You Sleep Better

"The oxytocin released during orgasm also promotes sleep, according to research.

And getting enough sleep has been linked with a host of other good things, such as maintaining a healthy weight and blood pressure. Something to think about, especially if you've been wondering why your guy can be active one minute and snoring the next."

Sex As Physical Exercise Also Promotes Sleep

"The physical exercise component of sex can also help you relax and sleep better, in addition to the hormonal effects. People who get regular exercise tend to sleep better and have more restful sleep. Moreover, as we have seen in the earlier part of this slideshow, sex is a great way to get some exercise." 

Summary

"Take note that sex is good for you in ways you may never have imagined and that the health benefits extend well beyond the bedroom."

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PD Patients Report Better Sleep With Rotigotine Tx

Patch form of dopamine agonist also lowered nighttime activity

SAN DIEGO -- The rotigotine patch (Neupro) appeared to objectively improve sleep quality in patients with Parkinson's disease with self-reported sleep complaints, Italian researchers said here.

Based on actigraph recordings, overall sleep efficiency was 67.8% in the week before treatment and 73.4% after 4 weeks of treatment with rotigotine patches for a statistically significant difference (P=0.017), according to Federica Provini, MD, of the University of Bologna, and colleagues.

In a poster presentation at Movement Disorders Society annual meeting, Provini's group noted that rotigotine is a dopamine agonist used for the treatment of motor symptoms in Parkinson's disease (PD) patients. Previous reports have suggested rotigotine use led to improvements in subjective sleep in PD patients with sleep complaints.

What was different in this pilot study was that the researchers used the actigraph, which records what really happens during sleep, to confirm the effectiveness of the patches.

"This is the first objective demonstration of rotigotine during sleep," said co-author Pietro Cortelli, MD, also at the University of Bologna. "Our study relied on the actigraph, not on questionnaires. The patients wore the actigraph 1 week before we treated, then we had the recording done after 4 weeks of treatment with rotigotine patches."

Cortelli told MedPage Today that the authors sought to show that the patches had an impact on the patient's sleep only. "We were not trying to determine if the patches improved motor function efficacy. We did not have a placebo group. We were just measuring their sleep efficiency," he said.

The patients were assessed using the Parkinson's Disease Sleep Scale, the Epworth Sleepiness Scale and the restless leg syndrome rating scale before the treatment. Their sleep was recorded with the actigraph to provide baseline data. The actigraph used was the Mini Motionlogger Actigraph Advanced by Ambulatory Monitoring.

Twelve of the 15 patients in the study were men and the mean age of all the participants was 67. They had been diagnosed with Parkinson's disease for a mean of 5 years. To be eligible for the study, the patients had to have registered sleep complaints and scored 10 or greater on the Parkinson's Disease Sleep Scale-2; a 3 or greater on the Hoehn and Yahr Score; and, prior to the study, could not have undergone treatment with rotigotine to control motor symptoms.

After 1 week without treatment, patients were treated with a 24-hour patch which was titrated over 1-4 weeks to the optimal dose to subjectively control motor symptom control. The starting patch contained 2 mg of rotigotine and the highest dose patch was 8 mg of rotigotine which was absorbed through the skin in 24 hours.

In addition to sleep efficiency, Provini told MedPage Today that there was a significant reduction in wake after sleep onset time (P=0.013). The wake after sleep onset time was 147.5 minutes in the week before using the patch and 106.5 minutes after the 1-month treatment trial, the researchers said. A longer wake after sleep onset is considered less efficient sleep quality.

The researcher also reported a reduction in the mean duration of wake episodes (P=0.005); improvement in the Unified Parkinson's Disease Rating Scale-III (P=0.018), and in the Parkinson's Disease Sleep Scale (P=0.005).

When looking at the patients who had pathological sleep efficiency pre-treatment, the authors reported a significant reduction in the nighttime activity mean (P=0.005) and activity median (P=0.04) post-treatment.

"This pilot study suggests that rotigotine subjectively improves sleep quality and [quality of life] in PD patients with self-eported sleep complaints and induces a significant reduction in nighttime activity, which could contribute to compromised sleep," the authors wrote, adding that in patients with reduced sleep efficiency, rotigotine objectively improved all sleep parameters.

Cortelli and Provini disclosed no relevant relationships with industry.

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ADA: Statins for Young T1D Patients, Too?

Heart risk in 30s might warrant statin use, observational data suggest

BOSTON -- Type 1 diabetes patients younger than 40 may be candidates for statin use, as guidelines recommend after age 40, researchers suggested.

Under the American Heart Association/American College of Cardiology definition, the 10-year cardiovascular risk was about 5% for type 1 diabetes patients ages 30 to 39 and about 13% in those ages 40 to 44, Rachel G. Miller, MD, of the University of Pittsburgh, and colleagues found.

Adding coronary revascularization to that definition -- which also included cardiovascular death or nonfatal stroke or myocardial infarction -- brought the 10-year risk to nearly 7% for type 1 diabetes patients in their 30s, the group reported here at the American Diabetes Association meeting.

Although still a little shy of the 7.5% 10-year risk threshold recommended for statin treatment in the guidelines, the 20% of the cohort already on a statin before age 40 was excluded along with a number of events that happened before the start of follow-up.

"We conclude that young adults aged 30 to 39 years with 20 or less years' type 1 diabetes duration are at sufficiently high atherosclerotic cardiovascular disease risk to merit statin therapy," the group concluded in their poster presentation.

Both the AHA/ACC and the American Diabetes Association guidelines recommend statins after 40 for essentially all diabetes patients and support possible use for younger people with cardiovascular disease risk factors.

"We've been comfortable with the concept that anybody over the age of 40 with type 2 should be on a statin and by extrapolation anybody who has type 1 over the age of 40 should be recommended for statins," commented Naveed Sattar, MD, a metabolic medicine specialist at the University of Glasgow, Scotland.

"What we now need is good guidance: Who are these people under 40 with type 1 who should get a statin, and how do we recognize them?"

There isn't enough data to develop a risk score for type 1 diabetes yet, he noted. Lifetime risk might be a better criterion in that population than the 10-year risks, which are heavily predicated upon age and which underpin current guidelines, Sattar noted.

"I think in the next 2 or 3 years either from national databases within Scandinavia or Scotland we're going to have a type 1 diabetes risk score that might allow us to look at this question," he suggested.

Comparisons with the general population in the surrounding county showed huge elevations in risk with type 1 diabetes even at these early ages, but absolute event numbers were small in Miller's study.

Among the 517 people under age 45 without pre-existing atherosclerotic cardiovascular disease followed from 1996 to 2011 in the Pittsburgh Epidemiology of Diabetes Complications study (a prospective group of childhood-onset cases seen at a single center soon after diagnosis):

• One event occurred in 20- to 29-year-olds
• 18 accrued in those in their 30s
• 22 occurred in participants in their early 40s

The fatal coronary artery event and nonfatal stroke or MI rates were 134 per 100,000 in the cohort ages 20 to 29, 502 per 100,000 people in their 30s, and 1,336 per 100,000 in the 40 to 44 age range.

Sattar cautioned against overinterpreting the "very crude analysis."

Miller disclosed no relevant relationships with industry. A co-author disclosed relationships with Eli Lilly and Company and Profil Institute for Clinical Research.

Sattar disclosed relationships with Amgen, AstraZeneca, and Sanofi.

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Study Questions Statin, Memory Loss Connection

Statin and nonstatin use both associated with increased complaints of memory loss

Beginning treatment with a statin was associated with a nearly fourfold increased risk of developing acute memory loss within 30 days in a retrospective cohort study, but a similar increase in risk was seen in patients starting non-statin lipid-lowering drugs.

Compared with non-users, both statin and non-statin lipid-lowering drug (LLD) use was found to be associated with acute memory loss in the weeks following treatment initiation, but there was no difference in memory loss when statins and non-statins were compared with each other, researcher Brian L. Strom, MD, of Rutgers University in Newark, N.J., and colleagues wrote online June 8 in JAMA Internal Medicine.

The observation that all LLDs were associated with memory loss suggests that either all drugs used to lower lipid levels cause acute memory loss or that the observed memory loss in the study was due to detection bias, Strom said.

In a telephone interview with MedPage Today, Strom said it makes sense that patients on a new drug would be more likely to notice symptoms and attribute them to the drug, and they are also more likely to report such symptoms to their physician.

"Patients might report a memory loss to me that they would otherwise pay little attention to because I am seeing them more often and I ask them about it," he said.

Earlier Statin, Memory Studies Mixed

Several previous studies have shown acute memory loss associated with the use of statins, but others have not shown the association or have even shown improved memory in long-term statin users compared with non-users.

Strom noted that without the non-statin LLD control group in his study, the findings would have shown a strong association between statin initiation and short-term memory loss.

"In the absence of this control group, the finding would have been completely misleading," he said.

The study included data obtained between early 1987 through late 2013 from The Health Improvement Network (THIN), which is a comprehensive database of medical records from general practitioners in the U.K. Patients were excluded from the analysis if they had a diagnosis of Alzheimer's disease or dementia, if they had received medications used for dementia, or if they had other conditions affecting cognition, such as Parkinson's disease, Huntington's disease, or vascular dementia.

The analysis compared 482,543 statin users with 482,543 matched non-users of any lipid-lowering drug (control group 1) and with 26,484 users of non-statin LLDs, such as cholestyramine, colestipol hydrochloride, colesevelam, clofibrate, gemfibrozil, and niacin (control group 2).

A secondary case-crossover analysis was performed that included 68,028 patients with incident acute memory loss whose exposure to statins was evaluated during the period immediately before the outcome versus three earlier periods (31 to 60 days prior, 150 to 180 days prior, and 270 to 300 days prior).

Non-statin LLD Users Had 3.6-Fold Risk Increase

The analysis revealed that:

• When compared with matched non-users of any LLDs, there was a strong association between first exposure to statins and acute memory loss within 30 days immediately following exposure (fully adjusted odds ratio 4.40, 95% CI 3.01-6.41).
• The association was not seen in the comparison of statin versus non-statin LLDs (fully adjusted OR 1.03, 95% CI 0.63-1.66).
• The association was seen in the first 30 days following exposure in non-statin LLD users compared with matched non-user controls (adjusted OR 3.60, 95% CI 1.34-9.70).
• Both atorvastatin and simvastatin showed an increased OR within the first 30 days after exposure compared with non-users (adjusted OR 2.40, 95% CI 1.42-4.04 and 3.53, 95% CI 2.79 -4.48, respectively).
• The case-crossover analysis showed a weak negative association, which was not found to be clinically meaningful.

A potential study limitation cited by the researchers involved a substantial difference in baseline characteristics between users of statins and users of non-statin LLDs, and differences among users of the various statin drugs.

"Bias from confounding by indication is the most serious potential problem in this study, even though we attempted to control for indication variables and a large number of other underlying conditions," the researchers wrote.

The case-crossover analysis was conducted to address this issue because each patient served as his or her own control.

Statin, Memory Issue 'Tempest in Teapot'

The researchers also noted that potential confounding could exist for variables not recorded in the medical records database.

Strom said the study findings should reassure both patients and physicians who prescribe statins.

"This whole issue of short-term memory loss with statins is really a tempest in a teapot," he said. "Statins are very effective drugs, and people should not veer away from them for fear of a short-term memory effect, especially given the data suggesting that long-term statin use improves memory."

The research was funded by the National Institutes of Health.

Strom reported receiving research funding from AstraZeneca and Bristol-Myers Squibb and serving as a consultant to Abbott, AstraZeneca, Bayer Healthcare, Bristol-Myers Squibb, Novartis and Pfizer. A co-author reported receiving research funding from AstraZeneca and Bristol-Myers Squibb and serving as a consultant to AstraZeneca, Bayer Healthcare, Bristol-Myers Squibb, and Merck.

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