High Blood Sugar Linked to Dementia

People with diabetes face an increased risk of Alzheimer’s disease and other forms of dementia, a connection scientists and physicians have worried about for years. They still can’t explain it.

Now comes a novel observational study of patients at a large health care system in Washington State showing that higher blood glucose levels are associated with a greater risk of dementia — even among people who don’t have diabetes. The results, published Thursday in The New England Journal of Medicine, “may have influence on the way we think about blood sugar and the brain,” said Dr. Paul Crane, the lead author and associate professor of medicine at the University of Washington.

The researchers tracked the blood glucose levels of 2,067 members of Group Health, a nonprofit HMO, for nearly seven years on average. Some patients had Type 2 diabetes when the study began, but most didn’t. None had dementia.

Over the years, as they saw doctors at Group Health, the participants received blood glucose tests. “It’s a common test in routine clinical practice,” Dr. Crane said. “We had an amazing opportunity with all this data. All the lab results since 1988 were available to us.”

The participants (average age at the start: 76) also reported to Group Health every other year for cognitive screening and, if their results were below normal, further testing and evaluation. Over the course of the study, about a quarter developed dementia of some kind, primarily Alzheimer’s disease or vascular dementia.

To measure blood sugar levels, the researchers combined glucose measurements, both fasting and nonfasting, with the HbA1c glycated hemoglobin assay, which provides a more accurate long-term picture. They also adjusted the data for other cardiovascular factors already linked to dementia, like high blood pressure and smoking.

“We found a steadily increasing risk associated with ever-higher blood glucose levels, even in people who didn’t have diabetes,” Dr. Crane said. Of particular interest: “There’s no threshold, no place where the risk doesn’t go up any further or down any further.” The association with dementia kept climbing with higher blood sugar levels and, at the other end of the spectrum, continued to decrease with lower levels.

This held true even at glucose levels considered normal. Among those whose blood sugar averaged 115 milligrams per deciliter, the risk of dementia was 18 percent higher than among those at 100 mg/dL, just slightly lower. The effects were also pronounced among those with diabetes: patients with average glucose levels of 190 mg/dL had a 40 percent higher risk of dementia than those whose levels averaged 160 mg/dL.

Though a longitudinal study like this one provides insight into the differences between people, it can’t explain why higher blood glucose might be connected to dementia, or tell individuals whether lower blood glucose is protective.

“People shouldn’t run for the hills or try crazy diets,” Dr. Crane cautioned. While an epidemiological study like this one can guide further exploration, he said, “This doesn’t show that changes in behavior that lower your individual blood sugar would decrease your individual risk of dementia.”

As for the blood glucose levels the study recorded, “clinically, they’re not big differences,” said Dr. Medha Munshi, a geriatrician and endocrinologist who directs the geriatric diabetes program at the Joslin Diabetes Center in Boston, who was not involved in the study. “I wouldn’t change my goals for diabetes management based on this study.” Nor would she warn someone whose blood glucose hits 115 mg/dL that he or she faces a greater risk of dementia.

But because diabetes itself can pose such a threat to health and quality of life, she still urges patients to adopt healthy practices like exercising regularly and maintaining a normal weight to try to avoid the disease. If by doing so they also lower their dementia risk — and knowing that would require a different study, focused on interventions — that would be a bonus.

This research “offers more evidence that the brain is a target organ for damage by high blood sugar,” said Dr. Munshi. “And everyone is still working on the ‘why’.

Chocolate may help keep brain healthy, sharp in old age, study says

Older chocoholics may have a new excuse to indulge their cravings: The dark stuff not only soothes the soul, but might also sharpen the mind. 

In a study published Wednesday in the journal Neurology, researchers reported that chocolate may help improve brain health and thinking skills in the elderly. The Boston-based team found that older people who initially performed poorly on a memory and reasoning test and also had reduced blood flow to their brains showed improvement after drinking two cups of cocoa every day for a month.  

The researchers had set out to test whether chocolate could increase blood flow to the brain during problem solving, boosting performance, after finding in earlier studies that consuming chocolate high in the antioxidant flavanol was associated with better brain and blood vessel functioning. They recruited 60 elderly subjects for the new study. Since they suspected that flavanol would improve the subjects’ thinking skills and blood flow, they randomly assigned subjects to drink either flavanol-rich or flavanol-poor hot chocolate.

The participants drank two cups of hot chocolate every day for 30 days. Before and after the study period, they completed a memory and reasoning test, which assessed their ability to recognize patterns in a series of letters on a computer screen. Additionally, the researchers used ultrasound to indirectly measure the blood flow to subjects’ brains, as well as magnetic resonance imaging, or MRI,  to examine subjects’ white matter — the nerve fibers that connect different parts of the brain.

People who performed poorly on the initial cognitive test — about a third of the participants — also had reduced blood flow to their brains and widespread white matter damage. Those who scored high on the test had signficantly better blood flow and more intact white matter, indicating that blood flow, cognitive functioning and brain structure were linked.

At the end of the 30 days, the team found that drinking hot chocolate benefited only the subjects who had poor cognitive and neurovascular function to begin with. After the hot cocoa regimen, those individuals showed an 8% improvement in blood flow and a roughly 1 minute faster reaction time on the cognitive task. There was barely any improvement among those who had started out with normal blood flow and cognitive skills.

To the scientists’ surprise, there weren’t significant differences in the neurovascular or cognitive changes between the flavanol-rich and flavanol-poor groups — suggesting that something else in the chocolate was causing the improvements. The researchers plan to identify and test this component in future trials, said study leader Dr.  Farzaneh A. Sorond, a neurologist at Brigham and Women’s Hospital in Boston.

After identifying the substance, the researchers may even be able to produce it in pill form, said Dr. Costantino Iadecola, a neurologist at Weill Cornell Medical College in New York City, who was not involved in the study.

By showing that blood flow to the brain is associated with cognitive function, the study helps explain earlier findings that people with high blood pressure and other cardiovascular conditions were prone to developing dementia. This, in turn, suggests that the cognitive functioning test and other measures used in the trial may one day serve as cheap, noninvasive methods to screen people for risk of dementia.

Scientists have focused more on treating than on preventing age-related cognitive decline, Sorond said.

“By the time people develop these problems, it’s too late to initiate the drugs we have,” she said. “If we could diagnose them earlier, before they have clinical symptoms, using physiological markers … maybe we could prevent the disease or lessen its impact.”

The study has its limitations. The ultrasound technique the researchers used offered only an estimate of blood flow to the brain – a precise measurement would require a more invasive method. “This was an easy way to get this information, but not the most accurate way,” Iadecola said.

He added that the study was small, and that it was unclear how long the chocolate’s effects would last.

“Will these changes persist after a month of cocoa or go back to where they were before? Would you take the cocoa forever?” Iadecola said. “We don’t know.”

Although the study results may tempt some to add chocolate to their diet,  Sorond noted that the participants’ food intake was strictly regulated to offset the excess fat and sugar in hot chocolate. For people seeking to keep their brains healthy, she recommends an intervention already known to improve cognitive function: exercise.

Religious Factors and Hippocampal Atrophy in Late Life

Despite a growing interest in the ways spiritual beliefs and practices are reflected in brain activity, there have been relatively few studies using neuroimaging data to assess potential relationships between religious factors and structural neuroanatomy. This study examined prospective relationships between religious factors and hippocampal volume change using high-resolution MRI data of a sample of 268 older adults. Religious factors assessed included life-changing religious experiences, spiritual practices, and religious group membership. Hippocampal volumes were analyzed using the GRID program, which is based on a manual point-counting method and allows for semi-automated determination of region of interest volumes. Significantly greater hippocampal atrophy was observed for participants reporting a life-changing religious experience. Significantly greater hippocampal atrophy was also observed from baseline to final assessment among born-again Protestants, Catholics, and those with no religious affiliation, compared with Protestants not identifying as born-again. These associations were not explained by psychosocial or demographic factors, or baseline cerebral volume. Hippocampal volume has been linked to clinical outcomes, such as depression, dementia, and Alzheimer’s Disease. The findings of this study indicate that hippocampal atrophy in late life may be uniquely influenced by certain types of religious factors.

Autism affects different parts of the brain in women and men

Autism affects different parts of the brain in females with autism than males with autism, a new study reveals. The research is published today in the journal Brain as an open-access article.

Scientists at the Autism Research Centre at the University of Cambridge used magnetic resonance imaging to examine whether autism affects the brain of males and females in a similar or different way. They found that the anatomy of the brain of someone with autism substantially depends on whether an individual is male or female, with brain areas that were atypical in adult females with autism being similar to areas that differ between typically developing males and females. This was not seen in men with autism.

“One of our new findings is that females with autism show neuroanatomical ‘masculinization’,” said Professor Simon Baron-Cohen, senior author of the paper. “This may implicate physiological mechanisms that drive sexual dimorphism, such as prenatal sex hormones and sex-linked genetic mechanisms.”

Autism affects 1% of the general population and is more prevalent in males. Most studies have therefore focused on male-dominant samples. As a result, our understanding of the neurobiology of autism is male-biased.

“This is one of the largest brain imaging studies of sex/gender differences yet conducted in autism. Females with autism have long been under-recognized and probably misunderstood,” said Dr Meng-Chuan Lai, who led the research project. “The findings suggest that we should not blindly assume that everything found in males with autism applies to females. This is an important example of the diversity within the ‘spectrum’.”

Dr Michael Lombardo, who co-led the study, added that although autism manifests itself in many different ways, grouping by gender may help provide a better understanding of this condition.

He said: “Autism as a whole is complex and vastly diverse, or heterogeneous, and this new study indicates that there are ways to subgroup the autism spectrum, such as whether an individual is male or female. Reducing heterogeneity via subgrouping will allow research to make significant progress towards understanding the mechanisms that cause autism.”

Researchers find caffeine during pregnancy negatively impacts mice brains

A team of European researchers has found that mice who consume caffeine while pregnant give birth to pups with negative changes to their brains. In their paper published in the journal Science Translational Medicine, the team reports on their findings after examining the brains of mice pups whose mothers were given caffeine during pregnancy.

Medical researchers have shown that drugs such as cocaine, heroin or even marijuana can have a negative impact on fetal development—in contrast most believe that moderate amounts of caffeine consumption during pregnancy is “safe” meaning it has little or no adverse impact on fetal development. This new study doesn’t change that view, but it does suggest that perhaps more research needs to be done.

In their study, the researchers administered the equivalent of 4 or 5 cups of coffee a day to pregnant mice—afterwards they studied the brains of the pups that were born. In so doing, they found that GABA neurons didn’t migrate during brain development to their proper location in the Hippocampus at the same rate as untreated mice. GABA neurons are responsible for controlling the flow of information in the brain. Subsequent tests found the treated pups to be more susceptible to seizures.

The team also found that if they allowed the treated pups to grow to adulthood, they tended to demonstrate problems with memory—instead of playing with new objects placed in their cages, for example, they were satisfied with playing with objects they already knew—a trait that is uncommon for mice. Autopsies of adult brains also showed fewer neurons in the Hippocampus.

The researchers point out that their results in mice are not necessarily applicable to humans and to reinforce that point another team of researchers also published a Focus piece in the same journal pointing out that there are significant differences in the developmental process of humans and mice fetuses and thus the study with mice has no real bearing on whether caffeine may or may not cause developmental problems with human babies.

Still, the results do indicate that perhaps more research should be done to find out if caffeine does indeed have an unknown negative impact on human fetal development.

Making connections in the eye

Wiring diagram of retinal neurons is first step toward mapping the human brain.

The human brain has 100 billion neurons, connected to each other in networks that allow us to interpret the world around us, plan for the future, and control our actions and movements. MIT neuroscientist Sebastian Seung wants to map those networks, creating a wiring diagram of the brain that could help scientists learn how we each become our unique selves.

In a paper appearing in the Aug. 7 online edition of Nature, Seung and collaborators at MIT and the Max Planck Institute for Medical Research in Germany have reported their first step toward this goal: Using a combination of human and artificial intelligence, they have mapped all the wiring among 950 neurons within a tiny patch of the mouse retina.

Composed of neurons that process visual information, the retina is technically part of the brain and is a more approachable starting point, Seung says. By mapping all of the neurons in this 117-micrometer-by-80-micrometer patch of tissue, the researchers were able to classify most of the neurons they found, based on their patterns of wiring. They also identified a new type of retinal cell that had not been seen before.

“It’s the complete reconstruction of all the neurons inside this patch. No one’s ever done that before in the mammalian nervous system,” says Seung, a professor of computational neuroscience at MIT.

Other MIT authors of the paper are former postdoc Srinivas Turaga and former graduate student Viren Jain. The Max Planck team was led by Winfried Denk, a physicist and the Max Planck Institute’s director. Moritz Helmstaedter, a research group leader at the Max Planck Institute, is the lead author of the paper, and Kevin Briggman, a former postdoc at Max Planck, is also an author.

Tracing connections

Neurons in the retina are classified into five classes: photoreceptors, horizontal cells, bipolar cells, amacrine cells and ganglion cells. Within each class are many types, classified by shape and by the connections they make with other neurons.

“Neurons come in many types, and the retina is estimated to contain 50 to 100 types, but they’ve never been exhaustively characterized. And their connections are even less well known,” Seung says.

In this study, the research team focused on a section of the retina known as the inner plexiform layer, which is one of several layers sandwiched between the photoreceptors, which receive visual input, and the ganglion cells, which relay visual information to the brain via the optic nerve. The neurons of the inner plexiform layer help to process visual information as it passes from the surface of the eye to the optic nerve.

To map all of the connections in this small patch of retina, the researchers first took electron micrographs of the targeted section. The Max Planck researchers obtained these images using a technique called serial block face scanning electron microscopy, which they invented to generate high-resolution three-dimensional images of biological samples.

Developing a wiring diagram from these images required both human and artificial intelligence. First, the researchers hired about 225 German undergraduates to trace the “skeleton” of each neuron, which took more than 20,000 hours of work (a little more than two years).

To flesh out the bodies of the neurons, the researchers fed these traced skeletons into a computer algorithm developed in Seung’s lab, which expands the skeletons into full neuron shapes. The researchers used machine learning to train the algorithm, known as a convolutional network, to detect the boundaries between neurons. Using those as reference points, the algorithm can fill in the entire body of each neuron.

“Tracing neurons in these images is probably one of the world’s most challenging computer vision problems. Our convolutional networks are actually deep artificial neural networks designed with inspiration from how our own visual system processes visual information to solve these difficult problems,” Turaga says.

If human workers were to fill in the entire neuron body, it would take 10 to 100 times longer than just drawing the skeleton. “This speeds up the whole process,” Seung says. “It’s a way of combining human and machine intelligence.”

The only previous complete wiring diagram, which mapped all of the connections between the 302 neurons found in the worm Caenorhabditis elegans, was reported in 1986 and required more than a dozen years of tedious labor.

“I think this is going to be a really significant paper in the history of how we study complex systems,” says Richard Masland, a professor of ophthalmology at the Massachusetts Eye and Ear Infirmary, who was not part of the research team. “This paper identifies circuit motifs that are interesting but really are just symbolic of the many types of questions that could be answered using these techniques.”

Classifying neurons

Wiring diagrams allow scientists to see where neurons connect with each other to form synapses — the junctions that allow neurons to relay messages. By analyzing how neurons are connected to each other, researchers can classify different types of neurons.

The researchers were able to identify most of the 950 neurons included in the new retinal-wiring diagram based on their connections with other neurons, as well as the shape of the neuron. A handful of neurons could not be classified because there was only one of their type, or because only a fragment of the neuron was included in the imaged sample.

“We haven’t completed the project of classifying types but this shows that it should be possible. This method should be able to do it, in principle, if it’s scaled up to a larger piece of tissue,” Seung says.

In this study, the researchers identified a new class of bipolar cells, which relay information from photoreceptors to ganglion cells. However, further study is needed to determine this cell type’s exact function.

Seung’s lab is now working on a wiring diagram of a larger piece of the retina — 0.3 millimeter by 0.3 millimeter — using a slightly different approach. In that study, the researchers first feed their electron micrographs into the computer algorithm, then ask human volunteers to check over the computer’s work and correct mistakes through a crowd-sourcing project known as EyeWire.

Our brains can (unconsciously) save us from temptation

Inhibitory self control – not picking up a cigarette, not having a second drink, not spending when we should be saving – can operate without our awareness or intention.

That was the finding by scientists at the University of Pennsylvania’s Annenberg School for Communication and the University of Illinois at Urbana-Champaign. They demonstrated through neuroscience research that inaction-related words in our environment can unconsciously influence our self-control. Although we may mindlessly eat cookies at a party, stopping ourselves from over-indulging may seem impossible without a deliberate, conscious effort. However, it turns out that overhearing someone – even in a completely unrelated conversation – say something as simple as “calm down” might trigger us to stop our cookie eating frenzy without realizing it.

The findings were reported in the journal Cognition by Justin Hepler, M.A., University of Illinois; and Dolores Albarracín, Ph.D., the Martin Fishbein Chair of Communication and a Professor of Psychology at Penn.

Volunteers completed a study where they were given instructions to press a computer key when they saw the letter “X” on the computer screen, or not press a key when they saw the letter “Y.” Their actions were affected by subliminal messages flashing rapidly on the screen. Action messages (“run,” “go,” “move,” “hit,” and “start”) alternated with inaction messages (“still,” “sit,” “rest,” “calm,” and “stop”) and nonsense words (“rnu,” or “tsi”). The participants were equipped with electroencephalogram recording equipment to measure brain activity.

The unique aspect of this test is that the action or inaction messages had nothing to do with the actions or inactions volunteers were doing, yet Hepler and Albarracín found that the action/inaction words had a definite effect on the volunteers’ brain activity. Unconscious exposure to inaction messages increased the activity of the brain’s self-control processes, whereas unconscious exposure to action messages decreased this same activity.

“Many important behaviors such as weight loss, giving up smoking, and saving money involve a lot of self-control,” the researchers noted. “While many psychological theories state that actions can be initiated automatically with little or no conscious effort, these same theories view inhibition as an effortful, consciously controlled process. Although reaching for that cookie doesn’t require much thought, putting it back on the plate seems to require a deliberate, conscious intervention. Our research challenges the long-held assumption that inhibition processes require conscious control to operate.”

The full article, “Complete unconscious control: Using (in)action primes to demonstrate completely unconscious activation of inhibitory control mechanisms,” will be available in the September issue of the journal.

(Image: Getty Images)