Depression, PTSD in Women Tied to Subsequent Dementia

Women with depression or posttraumatic stress disorder (PTSD) or who have experienced a traumatic brain injury (TBI) are at increased risk for subsequent dementia, new research suggests.

A cohort study of more than 100,000 female veterans showed that those who had one of these “military-related risk factors” at baseline were 50% to 80% more likely to develop dementia 4 years later than women without PTSD, TBI, or depression.

The findings were even more dire for those who had two or more of these risk factors, such as TBI with depression. For those women, the risk for developing dementia was doubled.

“These ‘military-related risk factors’ aren’t unique to the military, but military veterans have a probably 3 to 5 [times] greater chance of these exposures,” lead author Kristine Yaffe, MD, San Francisco Veterans Affairs (VA) Medical Center and Departments of Psychiatry, Neurology, and Epidemiology & Biostatistics at the University of California, San Francisco, told Medscape Medical News.

“This is the first study that I’m aware of looking at older women veterans and trying to understand what the risks are for getting dementia. And we think the findings are quite robust and important,” she added.

Dr Kristine Yaffe

Yaffe noted that the results may also be generalizable to nonveteran women.

“I think the biology is not different whether you’re a veteran or not. The difference here is just in the exposure. If you’re a military veteran, your chances are much higher you’ll be exposed” to these risk factors, she said.

The findings were published online November 12 in Neurology.

Disparity in the Field

Although past research has shown a significant link between dementia and TBI, PTSD, or depression, these studies “have been conducted almost exclusively among men,” the investigators write.

“This is a considerable disparity in the field, especially because more women are joining the military and female veterans may be at greater risk for certain psychiatric conditions compared to male veterans,” they add.

“It turns out that there is very little known about women veterans, particularly the older women. They just haven’t been asked to be part of research in any topic really,” said Yaffe.

For the current study, “we actually identified every female veteran who was 55 or older and who was getting their care at the VA,” she reported.

The investigators then assessed records from the National Patient Care Databases and the Vital Status File database for 109,140 female veterans who sought care from a US VA medical center between October 2004 and September 2015.

All of the included study participants (mean age, 68.5 years) completed at least one follow-up visit and were assessed at baseline for TBI, PTSD, depression, and comorbid conditions on the basis of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes.

At baseline, 488 of the women had TBI only, 1363 had PTSD only, 20,410 had depression only, 5044 had more than one military-related risk factor, and 81,835 had none of these risk factors.

ICD-9-CM codes from the 2016 version of the VA Dementia Steering Committee were used to determine dementia prevalence at baseline and dementia incidence at follow-up.

Increased Dementia Risk

During a mean follow-up of 4.0 years, 4% of the study participants developed dementia.

After adjusting for demographics and comorbid conditions such as diabetes mellitus, hypertension, and alcohol and tobacco use, there was a significantly greater risk for developing dementia in the women with vs without the following conditions:

  • PTSD: adjusted hazard ratio (HR), 1.78; 95% confidence interval [CI], 1.34 – 2.36;
  • Depression: HR, 1.67; 95% CI, 1.55 – 1.80; or
  • TBI: HR, 1.49; 95% CI, 1.01 – 2.20.

The investigators note that the finding that having a TBI increased dementia risk by 50% parallels “estimates from our prior study of male veterans in which TBI was similarly associated with a 60% increase in the risk of dementia.”

As for the almost 80% increased risk for dementia in the women with PTSD, “this is consistent with other investigations in male veterans that report an increase in risk of 80% to 100%,” the researchers write.

“There is [also] a robust body of evidence to support depression as a risk factor for developing dementia with studies in both community-based populations of women and (mostly male) veterans,” they add.

Yaffe noted that although their findings showed the highest risk for PTSD, followed by depression, and then TBI, “a ratio of 1.5 vs 1.8 may not be statistically different from one another. All three of the risk factors are important — and they often go together.”

The rates of incident dementia in those with TBI, depression, or PTSD only were 5.7%, 5.2%, and 3.9%, respectively, compared with 3.4% of the women who had no military-related risk factors (all comparisons, P < .001).

The incident dementia rate was 3.9% in the women who had more than one military-related risk factor; and their adjusted HR for dementia was 2.15 compared with those with none of the risk factors (95% CI, 1.84 – 2.51).

“These findings highlight the need for increased screening of TBI, PTSD, and depression in older women, especially female veterans,” the investigators write.

“If women have a history of PTSD or depression, they probably should be followed more closely and given periodic screening for their memory and other cognitive aspects as they get older,” Yaffe added.

In addition, these risk factors “are something we can maybe do something about. Certainly you can try to prevent traumatic brain injury with helmets and seat belts, and hopefully you can try to better treat PTSD and depression. And maybe all of this could actually decrease risk of dementia,” she said.

She noted that the study isn’t saying that an individual with one of these risk factors will definitively develop dementia. “It means that it increases your risk but it’s not a 1-to-1 correlation,” said Yaffe.

“Clear Need for More Studies”

In an accompanying editorial, Andrea L.C. Schneider, MD, PhD, and Geoffrey Ling, MD, PhD, from the Department of Neurology at Johns Hopkins University School of Medicine, Baltimore, Maryland and the Uniformed Services University of the Health Sciences, Bethesda, Maryland, note that although the study provides new evidence, it “also highlights that there is a clear need for more studies.”

They also point out that the “important findings” need to be confirmed and that causality needs to be determined.

“Future studies will need to include both men and women to assess directly for possible interaction by sex in associations between TBI, PTSD, and depression and dementia risk. Indeed, animal studies suggest sex differences in response to TBI and sex differences in the neurobiology of PTSD and depression,” they write.

“Given this, it is possible that neuropsychiatric conditions may be differentially associated with dementia risk in men vs in women,” they add.

The editorialists note that the study also relied only on ICD-9-CM codes to define the military-related risk factors and dementia — and that these codes are less sensitive than diagnostic interviews.

“It follows that a higher number of encounters with the health care system would make an individual have more opportunities to receive a diagnosis,” they write.

Overall, “a great deal more remains to be learned about the associations, underlying mechanisms, and possible sex differences in associations relating neuropsychiatric conditions…with dementia, both in military veteran populations and in general populations,” write Schneider and Ling.

“But importantly, the study by Yaffe et al. suggests that associations of TBI, PTSD, and depression with increased risk of dementia also occur in female military veterans and are not unique to male military veterans,” they conclude.

Low-Dose Propofol Safe for Headache

Hardly a shift goes by where I don’t see one or more patients complaining of headache. All too often these patients are no strangers to the ED; they’ve been seen multiple times for similar complaints.

Depending on who saw them previously, they may have been sent for yet another CT or even admitted for status migrainosus or further neurological evaluation. They invariably receive the standard headache cocktail that has permeated emergency medicine practice—an á la carte menu of a neuroleptic agent (prochlorperazine or metoclopramide top the list), ketorolac, diphenhydramine, and dexamethasone. That’s not without good reason—compelling data suggest that these agents are particularly effective in the emergency setting and even reduce headache recurrence. (Neurology 2017;89[20]:2075.)

But sometimes I just hate it. Don’t get me wrong; for many patients, maybe even most, the “headache cocktail” is a safe and effective option. But I find with increasing frequency that this witch’s brew does little more than sedate the patient for a few hours, and it may or may not address the underlying complaint. Sure, we get them discharged, but only after two long hours in a Compazine-induced haze, and the bed sits full while we wait.

There may be a better way for some patients. A growing body of literature and clinical experience has suggested low-dose propofol therapy as a safe and rapidly effective intervention for patients presenting with primary headache to the emergency department. Some hospital regulations may restrict the use of propofol or require more significant resource utilization when it’s used, but the practice is similar in many ways to the use of analgesic doses of ketamine, a practice that has become nearly routine in many EDs throughout the country.

Resolution of Symptoms

When propofol is administered until relief of pain, more than 80 percent of patients report complete resolution of symptoms, and they do so in a fraction of the time we’ve come to expect with traditional therapy. (Headache 2000;40[3]:224.)

I started using this strategy a few years ago. It’s not something I move to in every migraineur, and there’s likely a subset of patients more likely to benefit, as well as those in whom the standard antipsychotic approach probably offers a necessary secondary effect. I’ve encountered some administrative and nursing resistance, all of which has reliably evaporated once they’ve seen the therapy in action. I typically administer 10 mg IV every minute or so, monitoring the patient’s report of pain severity. Once the numbers begin to fall, I know that I’ve “broken” the headache. I have had nearly uniform response between 10-50 mg of medication.

Most patients experience mild drowsiness at most, and in my experience, as well as that seen in multiple retrospective analyses and randomized trials, there have been no adverse events. (BMC Neurology 2012;12[1]:114.) Following it with a dose of acetaminophen and an admonition to seek appropriate follow-up care, I’ve seen visit times fall and patient satisfaction rise, and I’ve yet to see the Diprivan-seeking bounceback patient about whom some skeptical colleagues warned me.

Once, after a particularly grueling set of night shifts, I awoke later in the afternoon to an email from a patient who described her long history of debilitating headaches that had seemed refractory to everything that had been thrown her way. Several weeks after I had treated her in the ED with low-dose propofol therapy, she was still headache-free, and, in fact, she reported that she was returning to work for the first time in years. It’s an anecdote, of course, but it’s true, and it made me proud to be an emergency physician and have the opportunity to bring cutting-edge care to the bedsides of my patients.

We emergency physicians are tasked with the dual roles of excluding life-threatening pathology while rendering effective pain relief and symptomatic care. Familiarity with a broad range of techniques for every complaint allows us to be safety-conscious and evidence-based while permitting the flexibility to provide individualized patient care. Low-dose propofol represents a safe, rapid, and effective addition to our armamentarium in treating patients with primary headache complaints in the emergency department.

Eating Leafy Greens Each Day Tied to Sharper Memory, Slower Decline

Scientists are keen to figure out how diet influences aging, including brain health. A five-year study of healthy seniors found those who ate a serving or two of daily greens had less cognitive decline.

To age well, we must eat well. There has been a lot of evidence that heart-healthy diets help protect the brain.

The latest good news: A study recently published in Neurology finds that healthy seniors who had daily helpings of leafy green vegetables — such as spinach, kale and collard greens — had a slower rate of cognitive decline, compared to those who tended to eat little or no greens.

“The association is quite strong,” says study author Martha Clare Morris, a professor of nutrition science at Rush Medical College in Chicago. She also directs the Rush Institute for Healthy Aging.

The research included 960 participants of the Memory and Aging Project. Their average age is 81, and none of them have dementia. Each year the participants undergo a battery of tests to assess their memory. Scientists also keep track of their eating habits and lifestyle habits.

To analyze the relationship between leafy greens and age-related cognitive changes, the researchers assigned each participant to one of five groups, according to the amount of greens eaten. Those who tended to eat the most greens comprised the top quintile, consuming, on average, about 1.3 servings per day. Those in the bottom quintile said they consume little or no greens.

After about five years of follow-up/observation, “the rate of decline for [those] in the top quintile was about half the decline rate of those in the lowest quintile,” Morris says.

So, what’s the most convenient way to get these greens into your diet?

“My goal every day is to have a big salad,” says Candace Bishop, one of the study participants. “I get those bags of dark, leafy salad mixes.”

A serving size is defined as a half-cup of cooked greens, or a cup of raw greens.

Does Bishop still feel sharp? “I’m still pretty damn bright,” she tells me with a giggle. She isn’t convinced that her daily salad explains her healthy aging.

“I think a lot of it is in the genes,” Bishop says, adding, “I think I’m lucky, frankly.”

She has other healthy habits, too. Bishop attends group exercise classes in her retirement community and she’s active on several committees in the community.

Many factors play into healthy aging — this study does not prove that eating greens will fend off memory decline. With this kind of research, Morris explains, scientists can only establish an association — not necessarily causation — between a healthy diet and a mind that stays sharp.

Still, she says, even after adjusting for other factors that might play a role, such as lifestyle, education and overall health, “we saw this association [between greens and a slower rate of cognitive decline] over and above accounting for all those factors.”

Some prior research has pointed to a similar benefit. A study of women published in 2006 also found that high consumption of vegetables was associated with less cognitive decline among older women. The association was strongest with greater consumption of leafy vegetables and cruciferous vegetables — such as broccoli and cauliflower.

And, as NPR has reported, there’s evidence that a Mediterranean-style diet — which emphasizes a pattern of eating that is rich in fish, nuts, vegetables and whole grains — may help stave off chronic diseases.

What might explain a benefit from greens?

Turns out, these vegetables contain a range of nutrients and bioactive compounds including vitamin E and K, lutein, beta carotene and folate.

“They have different roles and different biological mechanisms to protect the brain,” says Morris. More research is needed, she says, to fully understand their influence, but scientists know that consuming too little of these nutrients can be problematic.

For instance, “if you have insufficient levels of folate in your diet you can have higher levels of homocysteine,” Morris says. This can set the stage for inflammation and a buildup of plaque, or fatty deposits, inside your arteries, which increases the risk of stroke. Research shows elevated homocysteine is associated with cognitive impairment among older adults.

Another example: Getting plenty of Vitamin E from foods in your diet can help protect cells from damage and also has been associated with better cognitive performance.

“So, when you eat leafy greens, you’re eating a lot of different nutrients, and together they can have a powerful impact,” Morris says.

Blood Levels of Caffeine May Help Diagnose Parkinson’s

Blood levels of caffeine and its metabolites may be promising diagnostic biomarkers for early Parkinson’s disease, Japanese researchers reported.

Unrelated to total caffeine consumption or disease severity, serum levels of caffeine and nine of its downstream metabolites were significantly lower in patients with early Parkinson’s, Shinji Saiki, MD, PhD, of Juntendo University School of Medicine in Tokyo, and colleagues reported online in Neurology.

There were no significant genetic variations in the enzymes metabolizing caffeine between patients and controls.

Caffeine concentrations also were significantly decreased in Parkinson’s patients with motor fluctuations than in those without motor complications. However, patients in more severe disease stages did not have lower levels of caffeine, “suggesting that the decrease in caffeine metabolites occurs from the earliest stages of Parkinson’s,” David G. Munoz, MD, of the University of Toronto, and Shinsuke Fujioka, MD, of Fukuoka University in Japan, wrote in an accompanying editorial.

Some previous reports have suggested an inverse association between daily caffeine consumption and reduced risk of developing Parkinson’s, although a recent randomized controlled trial found no benefit to caffeine intake for Parkinson’s symptoms.

Mechanistically, caffeine could improve motor symptoms by antagonizing adenosine 2A receptors (A2A-Rs), but changes in the entire caffeine metabolic pathway in Parkinson’s patients are unclear.

In this study, researchers examined blood samples of 108 patients with idiopathic Parkinson’s disease and 31 age-matched healthy controls, separating caffeine and 11 downstream metabolites by high-performance liquid chromatography. All Parkinson’s patients had been treated at Juntendo University Hospital; on average, they had mild to moderate disease severity. Age, sex, and total caffeine intake were similar for both groups.

The researchers also recruited an additional 51 healthy controls and 67 Parkinson’s patients for gene analysis, screening for mutations in caffeine-associated genes by direct sequencing.

Blood levels of caffeine and nine of its 11 metabolites were lower in Parkinson’s patients than in controls (P<0.0001). The difference could be used to separate patients from controls reliably, with an area under the receiver operating characteristic curve of 0.98.

Analyses of caffeine-related genes showed no significant differences between patients and controls. The researchers saw no significant genetic variations in CYP1A2 or CYP2E1, the encoding cytochrome P450 enzymes primarily involved in metabolizing caffeine, between the groups. They found no associations between disease severity and single nucleotide variants of the ADORA2A gene, which encodes A2A-R.

They also detected no correlations between levodopa equivalent doses and absolute concentrations of caffeine and its metabolites.

One reason why early Parkinson’s patients had decreased caffeine levels may be related to intestinal absorption, the authors suggested. Gastrointestinal problems like constipation can affect up to 80% of Parkinson’s patients, sometimes preceding symptom onset by years, and a recent analysis showed that fecal microbial flora is altered in patients with Parkinson’s.

 “Although constipation and fecal bacterial change are predominantly attributed to large intestine function, caffeine absorption mainly occurs in the small intestine, where bacterial overgrowth in Parkinson’s is associated with levodopa malabsorption leading to motor fluctuations,” Saiki and colleagues observed.

Another explanation might be anti-parkinsonian agents.

“There is an elephant in the room: almost all patients with Parkinson’s were receiving treatment,” wrote Munoz and Fujioka. “The authors address this issue by finding no association between levels of caffeine metabolites and levodopa equivalent doses, but it is obvious that the validity of the study hangs on this point.”

“If a future study were to demonstrate similar decreases in caffeine in untreated patients with Parkinson’s, or persons with prodromal signs of Parkinson’s including REM behavior disorder, many of whom would be expected to develop Parkinson’s, the implications of the current study would take enormous importance,” they continued. This could lead to an easy test for early diagnosis or point to a basic mechanism of Parkinson’s pathogenesis.

One limitation of this study is that it did not include severe Parkinson’s cases; its reduced power may have limited the researchers’ ability to detect an association between disease severity and caffeine levels. Despite the lack of correlation between levodopa equivalent doses and caffeine concentration, Parkinson’s medications still might have affected metabolism, the authors added.

“Similar to a recent study showing progressive decreases in caffeine metabolites with disease exacerbation, de novo Parkinson’s studies including larger study populations and studies on differential diagnostic values among patients with Parkinson’s and other parkinsonian patients should be performed,” they wrote.

High Glucose Linked to Poorer Memory, Even in People Without Diabetes.

Higher levels of both short-term and long-term blood glucose markers are significantly associated with poorer memory and with decreased volume and microstructure of the hippocampus in persons without diabetes or impaired glucose tolerance (IGT), according to a new study.

The results imply that lowering blood glucose levels, possibly even to relatively low levels, might help preserve cognition, study author Agnes Flöel, MD, Department of Neurology and Center for Stroke Research Berlin, Charite-University Medicine, Berlin, Germany, toldMedscape Medical News.

Strategies that help lower blood glucose levels include a healthy Mediterranean-type diet and regular physical activity, she added.

The study is published online October 23 in Neurology.

Direct Relationship

The cross-sectional study included 141 healthy persons (mean age, 63.1 years) who were recruited through advertising. Persons with diabetes, IGT, or neurologic disorders and those taking antidepressants were excluded.

Researchers obtained blood measurements, including glycosylated hemoglobin (HbA1c), which reflects peripheral glucose levels of the preceding 8 to 12 weeks; fasting glucose; and insulin. They also carried out apolipoprotein E (APOE) genotyping.

Participants underwent cognitive testing using the German version of the Rey Auditory Verbal Learning Test. Researchers calculated hippocampal volume from MRI scans and assessed hippocampal microstructure by mean diffusivity (MD) estimated by using diffusion tensor imaging.

According to Dr. Flöel, this was the first time that this MD method provided data on the association between hippocampal microstructure and glucose metabolism.

The investigators found that lower performance on 3 memory tasks (delayed recall, learning ability, and consolidation) was associated with higher levels of both the long-term marker of glucose control (HbA1c) and the short-term glucose marker (all P ≤ .01).

For insulin, there was a “general trend going in the same direction” but correlations were less clear, and without the same direct relationship, said Dr. Flöel.

Potential Mechanisms

Memory performance was correlated with hippocampal volume (P = .001) and lower MD (P = .01), lower age, and, in part, lower blood pressure and female sex. Researchers did not find a statistically significant association between memory performance and APOE genotype, body mass index, Beck Depression Inventory score, physical activity, or smoking.

Lower levels of HbA1c were associated with larger hippocampal volume (nonsignificant trend; P = .06). The associations between lower fasting glucose levels and higher hippocampal volume did reach significance (P = .01). There was no significant relationship between hippocampal volume and insulin.

As for hippocampal microstructure, the researchers noted that lower levels of all 3 markers of glucose metabolism significantly correlated with lower MD within the hippocampus.

There was no significant association between glucose markers and volume or MD in brain areas other than the hippocampus (eg, gray matter and thalamus).

The hippocampus is particularly vulnerable to disturbances in metabolic supply, including glucose, said Dr. Flöel.

“Elevated blood sugar levels may damage the outer membrane of the cells, or decrease neurotransmitter levels, which would disturb signaling within and between hippocampal cells. Information transfer between cells, which is indispensable for memory encoding, storage and retrieval, would then be compromised.”

Elevated blood sugar levels may also damage small and large vessels in the brain, leading to decreased blood and nutrient flow to brain cells or even brain infarcts, and this may further damage memory-relevant brain structures, added Dr. Flöel.

The current findings are in line with studies of patients with type 2 diabetes mellitus and IGT, but earlier research was unable to confirm the deleterious effects of nondiabetic glucose levels on cognition. This, said the authors, may be because of different methods for classifying glucose levels and varying cognitive tests used.

Prevention Research

The authors also pointed out that the current study used MRI with higher magnetic field strength, which offers a higher sensitivity of hippocampal volumetry and greater statistical power to observe significant associations.

Following a diet high in lean protein and complex carbohydrates (such as whole grains, vegetables, fruits, and fiber) and low in heavily refined foods will help lower blood glucose, said Dr. Flöel. Another important lifestyle strategy is regular physical activity.

How low is it safe to go in terms of blood glucose levels? According to Dr. Flöel, that depends in part on lifestyle. “If you’re used to low blood sugar levels, you can go quite low,” she said.

She likened this to the situation with blood pressure. “At one time, it was assumed that you needed a certain level to function, but that actually is not true. You can go very low and still maintain normal function, and it might actually be better in the long run.”

Although the study uncovers the protective potential of lower blood glucose levels, the relationship between high blood glucose and poor memory “seems to be more linear” and changing recommended cutoffs may not make much of a difference, said Dr. Flöel.

On the other hand, what could be key is prevention, she said.

“There have been some initiatives to put prevention more on the agenda of dementia research,” she said. “There has been so much money spent on treatment of Alzheimer’s disease and it has already been established that this is not very successful. “

Dementia prevention strategies could include taking measures at an earlier stage to encourage physical fitness and control hypertension, blood lipids (including cholesterol and triglycerides), and now, possibly, blood glucose levels, she said.

Patients should have their fasting glucose and HbA1c levels measured as part of a regular medical check-up starting at age 55 years, unless there’s a personal or family history of diabetes or the patient is obese, in which case the family doctor may opt for earlier and more intense monitoring, said Dr. Flöel. She pointed out that such tests are easy to do and are already carried out regularly in pregnant women.

Fresh Eyes

Commenting on the findings for Medscape Medical News, Marwan N. Sabbagh, director, Banner Sun Health Research Institute, Sun City, Arizona, said that the study looks at the link between glucose metabolism and cognition with fresh eyes.

“This is saying that immediate learning and A1c levels, and potentially even blood sugars, interact even in people who are nondemented, and I don’t think anyone has looked at it that way before,” said Dr. Sabbagh.

“The idea is that the lower the A1c the better your brain function. This is a very exciting development and clearly helps put a frame around the Alzheimer’s discussion, but more importantly, it talks about how blood sugar metabolism and cognitive function directly interact.”

The study opens “a whole new territory” because until now, HbA1c and blood glucose have been looked at only in the context of diabetes and the risk for diabetes, added Dr. Sabbagh. “Maybe we need to rethink our normalization of glucose with an eye toward cognition and not simply a diabetes risk.”

Method of recording brain activity could lead to mind-reading devices.

A brain region activated when people are asked to perform mathematical calculations in an experimental setting is similarly activated when they use numbers — or even imprecise quantitative terms, such as “more than”— in everyday conversation, according to a study by Stanford University School of Medicine scientists.

Using a novel method, the researchers collected the first solid evidence that the pattern of brain activity seen in someone performing a mathematical exercise under experimentally controlled conditions is very similar to that observed when the person engages in quantitative thought in the course of daily life. 

“We’re now able to eavesdrop on the brain in real life,” said Josef Parvizi, MD, PhD, associate professor of neurology and neurological sciences and director of Stanford’s Human Intracranial Cognitive Electrophysiology Program. Parvizi is the senior author of the study, published Oct. 15 in Nature Communications. The study’s lead authors are postdoctoral scholar Mohammad Dastjerdi, MD, PhD, and graduate student Muge Ozker.

The finding could lead to “mind-reading” applications that, for example, would allow a patient who is rendered mute by a stroke to communicate via passive thinking. Conceivably, it could also lead to more dystopian outcomes: chip implants that spy on or even control people’s thoughts.

“This is exciting, and a little scary,” said Henry Greely, JD, the Deane F. and Kate Edelman Johnson Professor of Law and steering committee chair of the Stanford Center for Biomedical Ethics, who played no role in the study but is familiar with its contents and described himself as “very impressed” by the findings. “It demonstrates, first, that we can see when someone’s dealing with numbers and, second, that we may conceivably someday be able to manipulate the brain to affect how someone deals with numbers.”

The researchers monitored electrical activity in a region of the brain called the intraparietal sulcus, known to be important in attention and eye and hand motion. Previous studies have hinted that some nerve-cell clusters in this area are also involved in numerosity, the mathematical equivalent of literacy. 

However, the techniques that previous studies have used, such as functional magnetic resonance imaging, are limited in their ability to study brain activity in real-life settings and to pinpoint the precise timing of nerve cells’ firing patterns. These studies have focused on testing just one specific function in one specific brain region, and have tried to eliminate or otherwise account for every possible confounding factor. In addition, the experimental subjects would have to lie more or less motionless inside a dark, tubular chamber whose silence would be punctuated by constant, loud, mechanical, banging noises while images flashed on a computer screen.

“This is not real life,” said Parvizi. “You’re not in your room, having a cup of tea and experiencing life’s events spontaneously.” A profoundly important question, he said, is: “How does a population of nerve cells that has been shown experimentally to be important in a particular function work in real life?” 

His team’s method, called intracranial recording, provided exquisite anatomical and temporal precision and allowed the scientists to monitor brain activity when people were immersed in real-life situations. Parvizi and his associates tapped into the brains of three volunteers who were being evaluated for possible surgical treatment of their recurring, drug-resistant epileptic seizures.

The procedure involves temporarily removing a portion of a patient’s skull and positioning packets of electrodes against the exposed brain surface. For up to a week, patients remain hooked up to the monitoring apparatus while the electrodes pick up electrical activity within the brain. This monitoring continues uninterrupted for patients’ entire hospital stay, capturing their inevitable repeated seizures and enabling neurologists to determine the exact spot in each patient’s brain where the seizures are originating.

During this whole time, patients remain tethered to the monitoring apparatus and mostly confined to their beds. But otherwise, except for the typical intrusions of a hospital setting, they are comfortable, free of pain and free to eat, drink, think, talk to friends and family in person or on the phone, or watch videos.

The electrodes implanted in patients’ heads are like wiretaps, each eavesdropping on a population of several hundred thousand nerve cells and reporting back to a computer.

In the study, participants’ actions were also monitored by video cameras throughout their stay. This allowed the researchers later to correlate patients’ voluntary activities in a real-life setting with nerve-cell behavior in the monitored brain region. 

As part of the study, volunteers answered true/false questions that popped up on a laptop screen, one after another. Some questions required calculation — for instance, is it true or false that 2+4=5? — while others demanded what scientists call episodic memory — true or false: I had coffee at breakfast this morning. In other instances, patients were simply asked to stare at the crosshairs at the center of an otherwise blank screen to capture the brain’s so-called “resting state.”

Consistent with other studies, Parvizi’s team found that electrical activity in a particular group of nerve cells in the intraparietal sulcus spiked when, and only when, volunteers were performing calculations.

Afterward, Parvizi and his colleagues analyzed each volunteer’s daily electrode record, identified many spikes in intraparietal-sulcus activity that occurred outside experimental settings, and turned to the recorded video footage to see exactly what the volunteer had been doing when such spikes occurred.

They found that when a patient mentioned a number — or even a quantitative reference, such as “some more,” “many” or “bigger than the other one” — there was a spike of electrical activity in the same nerve-cell population of the intraparietal sulcus that was activated when the patient was doing calculations under experimental conditions. 

That was an unexpected finding. “We found that this region is activated not only when reading numbers or thinking about them, but also when patients were referring more obliquely to quantities,” said Parvizi.

“These nerve cells are not firing chaotically,” he said. “They’re very specialized, active only when the subject starts thinking about numbers. When the subject is reminiscing, laughing or talking, they’re not activated.” Thus, it was possible to know, simply by consulting the electronic record of participants’ brain activity, whether they were engaged in quantitative thought during nonexperimental conditions.

Any fears of impending mind control are, at a minimum, premature, said Greely. “Practically speaking, it’s not the simplest thing in the world to go around implanting electrodes in people’s brains. It will not be done tomorrow, or easily, or surreptitiously.”

Parvizi agreed. “We’re still in early days with this,” he said. “If this is a baseball game, we’re not even in the first inning. We just got a ticket to enter the stadium.”

– See more at:

Epilepsy Drug Warnings May Slip Through Cracks.

One-fifth of American neurologists are unaware of serious safety risks associated with epilepsydrugs and are potentially risking the health of patients who could be treated with safer medications, a new study reveals.

The 505 neurologists who took part in the survey between March and July 2012 were asked if they knew about several epilepsy drugs’ safety risks recently identified by the U.S. Food and Drug Administration.

These risks included increased danger of suicidal thoughts or behaviors linked with some newer drugs, a high risk for birth defects and mental impairment in children of mothers taking divalproex (brand nameDepakote), and the likelihood of serious hypersensitivity reactions in some Asian patients treated with carbamazepine (Tegretol).

One in five of the neurologists said they did not know about any of these risks. Neurologists who treat 200 or more epilepsy patients per year were most likely to know all the risks, according to the study, which was published online recently in the journal Epilepsy.

Although this study focused on epilepsy drugs, the findings suggest that the FDA needs to find better ways to inform doctors about newly discovered drug safety risks, said the researchers from Johns Hopkins University School of Medicine. Their results show that warnings about these risks are not getting through to doctors making important prescribing decisions.

There is no single place for neurologists to find updated drug risk information, said study leader Dr. Gregory Krauss, a professor of neurology. A few get emails from the FDA, while others get the information from neurology societies, continuing medical education courses or journal articles.

“There is poor communication from the FDA to specialists, and there’s some risk to patients because of this,” Krauss said in a Johns Hopkins news release.

“Unless it’s a major change requiring the FDA to issue a black box warning on a product, important information appears to be slipping through the cracks,” he said. “We need a more systematic and comprehensive method so that doctors receive updated safety warnings in a format that guarantees they will see and digest what they need to protect patients.”


Anemia Tied to Increased Dementia Risk.

Older adults who have anemia face increased risk for dementia, according to a prospective cohort study in Neurology.

Researchers studied some 2600 initially dementia-free older adults, 15% of whom had anemia at baseline. During 11 years’ follow-up, 18% of participants developed dementia. After adjustment for potential confounders such as age, sex, APOE genotype, comorbid conditions, and literacy, participants with anemia had a significant, 49% increase in risk for dementia relative to those without anemia.

The researchers say their findings are consistent with those from previous studies, and they suggest several possible mechanisms underlying the association. For example, the brain hypoxia that occurs with anemia might contribute to dementia risk, or anemia could be a marker of overall poor health. They call for additional research to determine whether hemoglobin levels should be the focus of prevention strategies.

Source: Neurology

Being a Lifelong Bookworm May Keep You Sharp in Old Age.

To keep their bodies running at peak performance, people often hit the gym, pounding away at the treadmill to strengthen muscles and build endurance. This dedication has enormous benefitsbeing in shape now means warding off a host of diseases when you get older. But does the brain work in the same way? That is, can doing mental exercises help your mind stay just as sharp in old age?


Experts say it’s possible. As a corollary to working out, people have begun joining brain gyms to flex their mental muscles. For a monthly fee of around $15, websites like and promise to enhance memory, attention and other mental processes through a series of games and brain teasers. Such ready-made mind exercises are an alluring route for people who worry about their ticking clock. But there’s no need to slap down the money right away—new research suggests the secret to preserving mental agility may lie in simply cracking open a book.

The findings, published online today in Neurology, suggest that reading books, writing and engaging in other similar brain-stimulating activities slows down cognitive decline in old age, independent of common age-related neurodegenerative diseases. In particular, people who participated in mentally stimulating activities over their lifetimes, both in young, middle and old age, had a slower rate of decline in memory and other mental capacities than those who did not.

Researchers used an array of tests to measure 294 people’s memory and thinking every year for six years years. Participants also answered a questionnaire about their reading and writing habits, from childhood to adulthood to advanced age. Following the participants’ deaths at an average age of 89, researchers examined their brains for evidence of the physical signs of dementia, such as lesions,plaques and tangles. Such brain abnormalities are most common in older people, causing them to experience memory lapses. They proliferate in the brains of people with Alzheimer’s disease, leading to memory and thinking impairments that can severely affect victims’ daily lives.

Using information from the questionnaire and autopsy results, the researchers found that any reading and writing is better than none at all. Remaining a bookworm into old age reduced the rate of memory decline by 32 percent compared to engaging in average mental activity. Those who didn’t read or write often later in life did even worse: their memory decline was 48 percent faster than people who spent an average amount of time on these activities.

The researchers found that mental activity accounted for nearly 15 percent of the difference in memory decline, beyond what could be explained by the presence of plaque buildup. “Based on this, we shouldn’t underestimate the effects of everyday activities, such as reading and writing, on our children, ourselves and our parents or grandparents,” says study author Robert S. Wilson, a neuropsychologist at the Rush University Medical Center in Chicagoin a statement.

Reading gives our brains a workout because comprehending text requires more mental energy than, for example, processing an image on a television screen. Reading exercises our working memory, which actively processes and stores new information as it comes. Eventually, that information gets transferred into long-term memory, where our understanding of any given material deepens. Writing can be likened to practice: the more we rehearse the perfect squat, the better our form becomes, tightening all the right muscles. Writing helps us consolidate new information for the times we may need to recall it, which boosts our memory skills.

So the key to keeping our brains sharp for the long haul does have something in common with physical exercise: we have to stick with it. And it’s best to start early. In 2009, a seven-year studyof 2,000 healthy individuals aged 18 to 60 found that mental agility peaks at 22. By 27, mental processes like reasoning, spatial visualization and speed of thought began to decline.




Blood-brain barrier disruption is associated with increased mortality after endovascular therapy.

OBJECTIVE: To evaluate the incidence, baseline characteristics, and clinical prognosis of blood-brain barrier (BBB) disruption after endovascular therapy in acute ischemic stroke patients.

METHODS: A total of 220 patients treated with endovascular therapy between April 2007 and October 2011 were identified from a prospective, clinical, thrombolysis registry. All patients underwent a nonenhanced CT scan immediately after treatment. CT scan or MRI was systematically realized at 24 hours to assess intracranial hemorrhage complications. BBB disruption was defined as a hyperdense lesion on the posttreatment CT scan.
RESULTS: BBB disruption was found in 128 patients (58.2%; 95% confidence interval [CI], 51.4%-64.9%). Cardioembolic etiology, high admission NIH Stroke Scale score, high blood glucose level, internal carotid artery occlusion, and use of combined endovascular therapy (chemical and mechanical revascularization) were independently associated with BBB disruption. Patients with BBB disruption had lower rates of early major neurologic improvement (8.6% vs 31.5%, p < 0.001), favorable outcome (39.8% vs 61.8%, p = 0.002), and higher rates of 90-day mortality (34.4% vs 14.6%, p = 0.001) and hemorrhagic complications (42.2% vs 8.7%, p < 0.001) than those without BBB disruption. By multivariable analysis, patients with BBB disruption remained with a lower rate of early neurologic improvement (adjusted odds ratio [OR], 0.28; 95% CI, 0.11-0.70) and with a higher rate of mortality (adjusted OR, 2.37; 95% CI, 1.06-5.32) and hemorrhagic complications (adjusted OR, 6.38; 95% CI, 2.66-15.28).
CONCLUSION: BBB disruption has a detrimental effect on outcome and is independently associated with mortality after endovascular therapy. BBB disruption assessment may have a role in prognosis staging in these patients.

Source: Neurology