1. Brain injury causes impulse control problems in rats

    May 24, 2017 by Ashley

    From the University of British Columbia press release:

    New research from the University of British Columbia confirms for the first time that even mild brain injury can result in impulse control problems in rats.

    The study, published in the Journal of Neurotrauma, also found that the impulsivity problems may be linked to levels of an inflammatory molecule in the brain, and suggest that targeting the molecule could be helpful for treatment.

    “Few studies have looked at whether traumatic brain injuries cause impulse control problems,” said the study’s lead author, Cole Vonder Haar, a former postdoctoral research fellow in the UBC department of psychology who is now an assistant professor at West Virginia University. “This is partly because people who experience a brain injury are sometimes risk-takers, making it difficult to know if impulsivity preceded the brain injury or was caused by it. But our study confirms for the first time that even a mild brain injury can cause impulse control problems.”

    For the study, researchers gave rats with brain injuries a reward test to measure impulsivity.

    Rats that were unable to wait for the delivery of a large reward, and instead preferred an immediate, but small reward, were considered more impulsive.

    The researchers found that impulsivity in the rats increased regardless of the severity of the brain injury. The impulsivity also persisted eight weeks after injury in animals with a mild injury, even after memory and motor function returned.

    “These findings have implications for how brain injury patients are treated and their progress is measured,” said Vonder Haar. “If physicians are only looking at memory or motor function, they wouldn’t notice that the patient is still being affected by the injury in terms of impulsivity.”

    After analyzing samples of frontal cortex brain tissue, the researchers also found a substantial increase in levels of an inflammatory molecule, known as interleukin-12, that correlated with levels of impulsivity. Interleukins are groups of proteins and molecules responsible for regulating the body’s immune system.

    The study builds on the researchers’ previous findings about the link between interleukin-12 and impulsivity.

    Catharine Winstanley, the study’s senior author and associate professor in the UBC department of psychology, said the findings are important because impulsivity is linked to addiction vulnerability.

    “Addiction can be a big problem for patients with traumatic brain injuries,” she said. “If we can target levels of interleukin-12, however, that could potentially provide a new treatment target to address impulsivity in these patients.”


  2. Brain’s power to adapt offers short-term gains, long-term strains

    May 9, 2017 by Ashley

    From the Penn State press release:

    Like air-traffic controllers scrambling to reconnect flights when a major hub goes down, the brain has a remarkable ability to rewire itself after suffering an injury. However, maintaining these new connections between brain regions can strain the brain’s resources, which can lead to serious problems later, including Alzheimer’s Disease, according to researchers.

    After a head injury, the brain can show enhanced connectivity by using alternative routes between two previously connected regions of the brain that need to communicate, as well as make stronger connections, said Frank G. Hillary, associate professor of psychology, Penn State. These new connections between damaged areas are often referred to as hyperconnections, he added.

    Hyperconnectivity has been called a compensatory reaction to brain injury and it’s a little counterintuitive because it implies that the brain can increase its functional response when you take away physical resources,” said Hillary. “If the axon — the physical connection — between brain areas is removed, the brain can retain that connection functionally by using alternative routes. So what we’re seeing is there are all sorts of ways in which the brain can adapt and one way is to heighten the response, but the question is what does that do for you in the short term and what are the potential secondary consequences in the long term.”

    Because neural networks are typically designed to communicate as efficiently as possible, disruptions may mean that new networks are less efficient and use more energy, said Hillary, who worked with Jordan H. Grafman, director, brain injury research at Shirley Ryan Abilitylab and professor of physical medicine and rehabilitation, neurology and psychiatry and behavioral sciences at the Northwestern University in Chicago.

    It’s costly metabolically and it’s costly with respect to how quickly you think,” said Hillary. “One of the primary cognitive deficits in all neurological disorders — multiple sclerosis, traumatic brain injury, schizophrenia — is impairments in how quickly you can think, called processing speed. In neurological disorders, processing speed diminishes and it can be related to a decrease in brain efficiency.”

    Over time, these chronic inefficiencies may cascade into serious brain disorders, according to the researchers, who report their findings in the current issue of Trends in Cognitive Science.

    “If we know which patients would be susceptible to pathological hyperconnectivity following a traumatic brain injury, we might be able to develop new interventions to alter the course of that process,” said Grafman. Prior research has suggested a connection between brain injury and Alzheimer’s Disease, according to the researchers.

    “We know that brain injury is a risk factor for Alzheimer’s Disease later in life and the long-term effect of hyperconnections may be a link to how it happens,” said Hillary, who also is a faculty member at Penn State College of Medicine.

    Just as inefficient motors tend to pollute more, inefficient neural connections may build up harmful deposits that can further impair the brain. Although other factors, such as genetics, are likely involved, the researchers noted that higher deposits of amyloid beta — a marker of Alzheimer’s Disease — are often located at sites where there is the highest connectivity.

    “Where there’s a lot of activity going on, it increases metabolic byproducts and if you don’t clear them, they collect,” said Hillary. “Heavy activation, heavy connectivity can put pressure on network hubs and that’s why those hubs are some of the first to go in Alzheimer’s.”

    While more research is needed and possible treatment targets for Alzheimer’s or other neurological conditions remain uncertain, Hillary said the findings underscore the need to take precautions against brain injury.

    “What I always tell my students is be good to your brain,” said Hillary. “You only get one brain and while it can adapt to some injuries over your life, there is probably a cost for those adjustments.”


  3. Study suggests traumatic brain injuries affect women differently

    April 8, 2017 by Ashley

    From the Endocrine Society press release:

    Traumatic brain injuries affect the body’s stress axis differently in female and male mice, according to research presented at the Endocrine Society’s 99th annual meeting, ENDO 2017, in Orlando, Fla. The results could help explain why women who experience blast injuries face a greater risk of developing mental health problems than men.

    About 1.5 million people are diagnosed with traumatic brain injury (TBI) each year. Blast injuries are particularly common in the military population. Between 15 percent and 30 percent of soldiers who experience a TBI are later diagnosed with neuropsychiatric disorders such as depression, anxiety or post-traumatic stress disorder (PTSD). Even though men are more likely to experience a TBI, women have an elevated risk of developing mental health disorders due to the injury.

    The study examined how blast injuries disrupt the stress axis, specifically the hypothalamic-pituitary-adrenal (HPA) axis, a signaling pathway involved in the body’s stress response. The hormones produced by the glands in the stress axis affect parts of the brain involved in regulating fear and anxiety.

    “The study suggests that mild blast traumatic brain injuries dysregulate the neuroendocrine stress axis differently in women and men,” said Ashley Russell, the first author and a Neuroscience Ph.D. candidate at the Uniformed Services University of the Health Sciences (USU) in Bethesda, Md. “The research provides a missing link between a mild blast injury and the subsequent development of neuropsychiatric disorders such as anxiety and PTSD.”

    Researchers exposed both male and female mice to a mild blast injury of 15 psi using the ORA Advanced Blast Simulator at USU. When compared to mice that did not receive blast injury, injured mice produced altered levels of corticosterone, a hormone released when the stress axis is activated. This difference in the stress response was observed both short- and long-term post blast injury. Blast-injured female mice showed greater dysregulation of corticosterone levels than male mice with TBI.

    The scientists also sought to examine how a stressor may alter activation of corticotropin releasing factor (CRF) neurons in various brain regions involved in fear and anxiety regulation. In response to a stressor, female mice had heightened activation of CRF neurons in the stress integration center of the brain compared to male mice, an effect attributed to circulating estrogen levels.

    Understanding precisely how TBI can interfere with the body’s stress response may open the door to developing better interventions to treat both TBI and the resulting mental health conditions, Russell said.

    “Traumatic brain injury causes short- and long-term neuroendocrine dysregulation that may result in anxiety- and stress-related disorders,” she said. “Unfortunately, there are no therapeutic interventions to mitigate this response. More research is needed in this area to determine why these effects occur and how to treat them.”


  4. Potential drugs and targets for brain repair

    April 3, 2017 by Ashley

    From the PLOS press release:

    Researchers have discovered drugs that activate signaling pathways leading to specific adult brain cell types from stem cells in the mouse brain, according to a study publishing on 28 March in the open access journal PLOS Biology by Kasum Azim of the University of Zurich and colleagues from INSERM/university of Lyon and University of Portsmouth. The results may open new avenues for drug development aimed at treatment of degenerative brain disorders.

    New neurons, and support cells called oligodendrocytes, arise during development throughout adulthood from neural stem cells in the subventricular zone, a region of the forebrain adjacent to the ventricles. The transcriptional changes associated with the development of each cell type in the newborn mouse have been catalogued in publicly accessible databases. Similarly, the transcriptional changes produced by thousands of chemicals approved for clinical use have also been catalogued. In the new study, the authors used these databases (which included their own previously generated data) to find overlaps between transcriptional changes associated with cell differentiation and drug treatments, on the premise that these might identify potential therapies to reverse neurodegenerative diseases.

    Toward that end, they characterized differences in signaling pathways in “microdomains” of the subventricular zone where neurons or oligodendrocytes get their start in life. They found several potentially important differences between neuron-specific and oligodendrocyte-specific microdomains, and used these findings to identify similar changes in gene expression in the small molecule drug database.

    That led them to a set of small molecule drugs whose transcriptional signatures were similar to those of either neuronal or oligodendrocytic development. They showed that one such molecule, called LY-294002 specifically enhanced normal oligodendrogenesis from neural stem cells in newborn mice. In adult mice, different molecules (AR-A014418 and CHIR99021) counteracted the gradual loss of neurogenic capacity and lineage diversity of the adult subventricular zone. Finally, this later molecule promoted robust regeneration of oligodendrocytes and a smaller increase in neurons in a model of perinatal hypoxic brain injury.

    These results may be valuable in several ways. First, because the small molecule drug data point to important cellular pathways, they provide new insights into the mechanisms of neural development and repair, which can be exploited to develop new strategies for treatment. Second, they identify several new drugs, each already approved for clinical use, whose therapeutic potential for brain injury repair can now be explored. Finally, they provide a proof-of-principle for a novel approach to identify other potentially valuable new drugs that can directly affect neural regeneration, and that may be developed for treating brain diseases.

    “Controlling the fate of neural stem cells is a key therapeutic strategy in regenerative medicine,” said Azim and coworkers. “The strategy outlined in this study may allow us to quickly identify multiple drug candidates and get them into the drug development pipeline, where their potential as treatments can then be further assessed.”


  5. Biomechanical analysis of head injury in pediatric patients

    March 30, 2017 by Ashley

    From the Journal of Neurosurgery Publishing Group press release:

    The biomechanics of head injury in youths (5 to 18 years of age) have been poorly understood. A new study reported in the Journal of Neurosurgery: Pediatrics set out to determine what biomechanical characteristics predispose youths with concussions to experience transient or persistent postconcussion symptoms.

    Background. A form of traumatic brain injury, concussion is usually caused by a blow to the head or some other event that causes the brain to suddenly shift position within the skull. Various symptoms are associated with concussion: headache, dizziness, confusion, visual problems, concentration difficulties, irritability, depression, and more. Some young patients experience concussion-related symptoms for only a short time, but for others, symptoms linger. When symptoms resolve within a few weeks after the incident, they are known as transient post-concussion symptoms (TPCSs); when three or more concussion-related symptoms last more than four weeks after the incident, they are called persistent post-concussion symptoms (PPCSs).

    The Study. To determine the biomechanics of head impacts leading to transient or persistent post-concussion symptoms in youths, a Canadian group of concussion researchers recruited patients 5 to 18 years of age, who had been treated for concussion at any of nine emergency departments within the Pediatric Emergency Research Canada (PERC) network. A questionnaire about the incident was completed by patients or their parents/guardians; the questions elicited information about the type of head impact, what surface impacted the head, and what area of the head was impacted, as well as a detailed description of the event. Based on the information provided by the questionnaires, the researchers were able to reconstruct individual head-impact events in their laboratory. Completed questionnaires from 233 pediatric patients (182 with TPCSs and 51 with PPCSs) had sufficient information to recreate the head-impact event.

    The reconstructions of concussion scenarios were restricted to head impacts resulting from a vertical, gravity-related fall — onto the floor, grass, or ice, for example. Falls may have occurred in the home or during a sports event, from a height or standing position. Youths may have worn helmets or been bareheaded at the time of impact. All of this information was taken into account in the reconstruction.

    To simulate head impacts in youths with transient or persistent symptoms, the researchers used a headform, approximately the size of the patient’s head, and a monorail drop rig that dropped the headform onto an anvil at an impact velocity estimated for each head-impact incident. The surface of the anvil impacted by the headform was covered by material corresponding to the surface struck by the patient’s head: concrete, hardwood, grass, ice, etc. The angle of the headform when dropped was adjusted so that the area of impact on the headform corresponded to the site of impact on the patient’s head. If the patient had been wearing a helmet and/or mask at the time of injury, a similar helmet or mask was used in the simulation.

    In addition to physical models of head impact, the researchers used computational and finite element models to determine force, energy, peak linear and rotational acceleration, and maximal principal strain in brain tissue, and to measure cumulative strain damage associated with falls in the young patients. The researchers then compared values for these variables between patients with TPCSs and those with PPCSs. They found no statistically significant differences between the two patient groups for any of these variables.

    The researchers also examined whether one or more of the biomechanical variables could predict the occurrence of persistent symptoms (PPCSs). Again they found no statistically significant evidence that any of the biomechanical variables examined led to PPCSs, although “a trend shown for some variables indicated larger magnitudes of response were associated with PPCSs.”

    An important finding in these pediatric patients was “higher brain tissue strain responses for lower energy and impact velocities than those measured in adults, suggesting that youths are at higher risk of concussive injury at lower event severities.”

    Using the same techniques in head-injured adults, the researchers previously were able to identify statistically significant differences between patient groups. They offer several suggestions as to why this was not the case with youths and suggest other means by which one may be able to differentiate TPCSs from PPCSs, such as structural magnetic resonance imaging, diffusion tensor imaging, and arterial spin labeling. They also pose the possibility that PPCSs may be related more to the amount of brain tissue altered by the injury than to symptomology. Future biomechanical studies of pediatric brain injury, the investigators suggest, should include quantitative measures of the injury linked to clinical outcomes, patient predisposition, and history of concussion.

    Although this study was unable to definitively identify biomechanical variables that differentiate between TPCSs and PPCSs in youths, the researchers believe it is the first biomechanical analysis of a large number of pediatric concussion cases. Thus the data collected can be used in later investigations of youth concussions, both as a reference for future studies and as validation of the physical and computation models that were used.

    Details of the study are reported in the article, “Pediatric concussion: biomechanical differences between outcomes of transient and persistent (> 4 weeks) postconcussion symptoms,” by Andrew Post, Ph.D., and colleagues (published online today in the Journal of Neurosurgery: Pediatrics).

    When asked about the importance of this paper, Dr. Post stated, “This work is the first to examine the biomechanics of brain injury for youth using these types of methods. It has provided the first look into the mechanics of injury and provides a detailed dataset from which to improve our understanding of brain trauma in pediatric populations.”


  6. Children prenatally exposed to alcohol more likely to have academic difficulties

    March 28, 2017 by Ashley

    From the Research Society on Alcoholism:

    Despite greater awareness of the dangers of prenatal exposure to alcohol, the rates of Fetal Alcohol Spectrum Disorders remain alarmingly high. This study evaluated academic achievement among children known to be prenatally exposed to maternal heavy alcohol consumption as compared to their peers without such exposure, and explored the brain regions that may underlie academic performance.

    Researchers assessed two groups of children, eight to 16 years of age: 67 children with heavy prenatal alcohol exposure (44 boys, 23 girls) and 61 children who were not prenatally exposed to alcohol (33 boys, 28 girls). Scores on standardized tests of academic areas such as reading, spelling, and math were analyzed. In addition, a subsample of 42 children (29 boys, 13 girls) had brain imaging, which allowed the authors to examine the relations between the cortical structure (thickness and surface area) of their brains and academic performance.

    The alcohol-exposed children performed significantly worse than their peers in all academic areas, with particular weaknesses found in math performance. Brain imaging revealed several brain surface area clusters linked to math and spelling performance. The children without prenatal alcohol exposure demonstrated the expected developmental pattern of better scores associated with smaller brain surface areas, which may be related to a typical developmental process known as pruning. However, alcohol-exposed children did not show this pattern, possibly due to atypical or delayed brain development, which has been observed in other research studies. These results support previous findings of lower academic performance among children prenatally exposed to alcohol compared to their peers, which appear to be associated with differences in brain development, and highlight the need for additional attention and support for these children.


  7. Researchers identify how inflammation spreads through the brain after injury

    March 26, 2017 by Ashley

    From the University of Maryland School of Medicine press release:

    Researchers have identified a new mechanism by which inflammation can spread throughout the brain after injury. This mechanism may explain the widespread and long-lasting inflammation that occurs after traumatic brain injury, and may play a role in other neurodegenerative diseases.

    The findings were published today in a study in the Journal of Neuroinflammation.

    This new understanding has the potential to transform how brain inflammation is understood, and, ultimately, how it is treated. The researchers showed that microparticles derived from brain inflammatory cells are markedly increased in both the brain and the blood following experimental traumatic brain injury (TBI). These microparticles carry pro-inflammatory factors that can activate normal immune cells, making them potentially toxic to brain neurons. Injecting such microparticles into the brains of uninjured animals creates progressive inflammation at both the injection site and eventually in more distant sites.

    Research has found that neuroinflammation often goes on for years after TBI, causing chronic brain damage. The researchers say that the microparticles may play a key role in this process.

    Chronic inflammation has been increasingly implicated in the progressive cell loss and neurological changes that occur after TBI. These inflammatory microparticles may be a key mechanism for chronic, progressive brain inflammation and may represent a new target for treating brain injury.

    The researchers on the paper include four University of Maryland School of Medicine researchers: Alan Faden, Stephen R. Thom, Bogdan A. Stoica, and David Loane.

    “These results potentially provide a new conceptual framework for understanding brain inflammation and its relationship to brain cell loss and neurological deficits after head injury, and may be relevant for other neurodegenerative disorders such as Alzheimer disease in which neuroinflammation may also play a role,” said Dr. Faden. “The idea that brain inflammation can trigger more inflammation at a distance through the release of microparticles may offer novel treatment targets for a number of important brain diseases.”

    The researchers studied mice, and found that in animals who had a traumatic brain injury, levels of microparticles in the blood were much higher. Because each kind of cell in the body has a distinct fingerprint, the researchers could track exactly where the microparticles came from. The microparticles they looked at in this study are released from cells known as microglia, immune cells that are common in the brain. After an injury, these cells often go into overdrive in an attempt to fix the injury. But this outsized response can change protective inflammatory responses to chronic destructive ones.

    The findings have important potential clinical implications. The researchers say that microparticles in the blood have the potential to be used as a biomarker — a way to determine how serious a brain injury may be. This could help guide treatment of the injuries, whose severity is often difficult to gauge.

    They also found that exposing the inflammatory microparticles to a compound called PEG-TB could neutralize them. This opens up the possibility of using that compound or others to treat TBI, and perhaps even other neurodegenerative diseases.


  8. Head injuries can alter hundreds of genes and lead to serious brain diseases

    March 23, 2017 by Ashley

    From the UCLA press release:

    Head injuries can harm hundreds of genes in the brain in a way that increases people’s risk for a wide range of neurological and psychiatric disorders, UCLA life scientists report.

    The researchers identified for the first time master genes that they believe control hundreds of other genes which are linked to Alzheimer’s disease, Parkinson’s disease, post-traumatic stress disorder, stroke, attention deficit hyperactivity disorder, autism, depression, schizophrenia and other disorders.

    Knowing what the master genes are could give scientists targets for new pharmaceuticals to treat brain diseases. Eventually, scientists might even be able to learn how to re-modify damaged genes to reduce the risk for diseases, and the finding could help researchers identify chemical compounds and foods that fight disease by repairing those genes.

    “We believe these master genes are responsible for traumatic brain injury adversely triggering changes in many other genes,” said Xia Yang, a senior author of the study and a UCLA associate professor of integrative biology and physiology.

    Genes have the potential to become any of several types of proteins, and traumatic brain injury can damage the master genes, which can then lead to damage of other genes.

    That process can happen in a couple of ways, said Yang, who is a member of UCLA’s Institute for Quantitative and Computational Biosciences. One is that the injury can ultimately lead the genes to produce proteins of irregular forms. Another is to change the number of expressed copies of a gene in each cell. Either change can prevent a gene from working properly. If a gene turns into the wrong form of protein, it could lead to Alzheimer’s disease, for example.

    “Very little is known about how people with brain trauma — like football players and soldiers — develop neurological disorders later in life,” said Fernando Gomez-Pinilla, a UCLA professor of neurosurgery and of integrative biology and physiology, and co-senior author of the new study. “We hope to learn much more about how this occurs.”

    The research appears in EBioMedicine, a journal published by Cell and The Lancet.

    The researchers trained 20 rats to escape from a maze. They then used a fluid to produce a concussion-like brain injury in 10 of the rats; the 10 others did not receive brain injuries. When the rats were placed in the maze again, those that had been injured took approximately 25 percent longer than the non-injured rats to solve it.

    To learn how the rats’ genes had changed in response to the brain injury, the researchers analyzed genes from five animals in each group. Specifically, they drew RNA from the hippocampus, which is the part of the brain that helps regulate learning and memory, and from leukocytes, white blood cells that play a key role in the immune system.

    In the rats that had sustained brain injuries, there was a core group of 268 genes in the hippocampus that the researchers found had been altered, and a core group of 1,215 genes in the leukocytes that they found to have been changed.

    “A surprise was how many major changes occurred to genes in the blood cells,” Yang said. “The changes in the brain were less surprising. It’s such a critical region, so it makes sense that when it’s damaged, it signals to the body that it’s under attack.”

    Nearly two dozen of the altered genes are present in both the hippocampus and the blood, which presents the possibility that scientists could develop a gene-based blood test to determine whether a brain injury has occurred, and that measuring some of those genes could help doctors predict whether a person is likely to develop Alzheimer’s or other disorders. The research could also lead to a better way to diagnose mild traumatic brain injury.

    More than 100 of the genes that changed after the brain injury have counterparts in humans that have been linked to neurological and psychiatric disorders, the researchers report. For example, 16 of the genes affected in the rats have analogs in humans, and those genes are linked to a predisposition for Alzheimer’s, the study reports. The researchers also found that four of the affected genes in the hippocampus and one in leukocytes are similar to genes in humans that are linked to PTSD.

    Yang said the study not only indicated which genes are affected by traumatic brain injury and linked to serious disease, but also might point to the genes that govern metabolism, cell communication and inflammation — which might make them the best targets for new treatments for brain disorders.

    The researchers now are studying some of the master genes to determine whether modifying them also causes changes in large numbers of other genes. If so, the master genes would be even more promising as targets for new treatments. They also plan to study the phenomenon in people who have suffered traumatic brain injury.

    In a 2016 study, Yang, Gomez-Pinilla and colleagues reported that hundreds of genes can be damaged by fructose and that an omega-3 fatty acid called docosahexaenoic acid, or DHA, seems to reverse the harmful changes produced by fructose. One of the genes they identified in that study, Fmod, also was among the master regulator genes identified in the new research.

    Not everyone with traumatic brain injuries develops the same diseases, but more severe injuries can damage more genes, said Gomez-Pinilla, who also is a member of UCLA’s Brain Injury Research Center.

     


  9. Rapid blood pressure drops in middle age linked to dementia in old age

    March 14, 2017 by Ashley

    From the Johns Hopkins University Bloomberg School of Public Health media release:

    Middle-aged people who experience temporary blood pressure drops that often cause dizziness upon standing up may be at an increased risk of developing cognitive decline and dementia 20 years later, new Johns Hopkins Bloomberg School of Public Health research suggests.

    The findings, being presented March 10 at the American Heart Association’s EPI|LIFESTYLE 2017 Scientific Sessions in Portland, Ore., suggest that these temporary episodes — known as orthostatic hypotension — may cause lasting damage, possibly because they reduce needed blood flow to the brain. Previous research has suggested a connection between orthostatic hypotension and cognitive decline in older people, but this appears to be the first to look at long-term associations.

    “Even though these episodes are fleeting, they may have impacts that are long lasting,” says study leader Andreea Rawlings, PhD, MS, a post-doctoral researcher in the Department of Epidemiology at the Bloomberg School. “We found that those people who suffered from orthostatic hypotension in middle age were 40 percent more likely to develop dementia than those who did not. It’s a significant finding and we need to better understand just what is happening.”

    An estimated four million to five million Americans currently have dementia and, as the population ages, that number is only expected to grow. There currently is no treatment and no cure for the condition.

    For the study, the researchers analyzed data from the Atherosclerosis Risk in Communities (ARIC) cohort, a study of 15,792 residents in four communities in the United States, who were between the ages of 45 and 64 when the study began in 1987. For this study, they focused on the 11,503 participants at visit one who had no history of coronary heart disease or stroke. After 20 minutes lying down, researchers took the participants’ blood pressure upon standing. Orthostatic hypotension was defined as a drop of 20 mmHg or more in systolic blood pressure or 10 mmHg or more in diastolic blood pressure. Roughly six percent of participants, or 703 people, met the definition.

    These participants, who were on average 54 years old upon enrolling in the study, continued to be followed over the next 20 or more years. People with orthostatic hypotension at the first visit were 40 percent more likely to develop dementia than those who did not have it. They had 15 percent more cognitive decline.

    Rawlings says it is not possible to tease out for certain whether the orthostatic hypotension was an indicator of some other underlying disease or whether the drop in blood pressure itself is the cause, though it is likely that the reduction in blood flow to the brain, however temporary, could have lasting consequences.

    It also wasn’t clear, she says, whether these participants had repeated problems with orthostatic hypotension over many years or whether they had just a brief episode of orthostatic hypotension at the original enrollment visit, as patients were not retested over time.

    “Identifying risk factors for cognitive decline and dementia is important for understanding disease progression, and being able to identify those most at risk gives us possible strategies for prevention and intervention,” Rawlings says. “This is one of those factors worth more investigation.”


  10. Benzodiazepines, related drugs increase stroke risk among persons with Alzheimer’s disease

    January 25, 2017 by Ashley

    From the University of Eastern Finland media release:

    memory lossThe use of benzodiazepines and benzodiazepine-like drugs was associated with a 20 per cent increased risk of stroke among persons with Alzheimer’s disease, shows a recent study from the University of Eastern Finland. Benzodiazepines were associated with a similar risk of stroke as benzodiazepine-like drugs.

    The use of benzodiazepines and benzodiazepine-like drugs was associated with an increased risk of any stroke and ischemic stroke, whereas the association with hemorrhagic stroke was not significant. However, due to the small number of hemorrhagic stroke events in the study population, the possibility of such an association cannot be excluded. The findings are important, as benzodiazepines and benzodiazepine-like drugs were not previously known to predispose to strokes or other cerebrovascular events. Cardiovascular risk factors were taken into account in the analysis and they did not explain the association.

    The findings encourage a careful consideration of the use of benzodiazepines and benzodiazepine-like drugs among persons with Alzheimer’s disease, as stroke is one of the leading causes of death in this population group. Earlier, the researchers have also shown that these drugs are associated with an increased risk of hip fracture.

    The study was based on data from a nationwide register-based study (MEDALZ) conducted at the University of Eastern Finland in 2005-2011. The study population included 45,050 persons diagnosed with Alzheimer’s disease, and 22 per cent of them started using benzodiazepines or benzodiazepine-like drugs.

    The findings were published in International Clinical Psychopharmacology.