Posts tagged neuroscience

The degeneration of a small, wishbone-shaped structure deep inside the brain may provide the earliest clues to future cognitive decline, long before healthy older people exhibit clinical symptoms of memory loss or dementia, a study by researchers with the UC Davis Alzheimer’s Disease Center has found.

The longitudinal study found that the only discernible brain differences between normal people who later developed cognitive impairment and those who did not were changes in their fornix, an organ that carries messages to and from the hippocampus, and that has long been known to play a role in memory.

“This could be a very early and useful marker for future incipient decline,” said Evan Fletcher, the study’s lead author and a project scientist with the UC Davis Alzheimer’s Disease Center.

“Our results suggest that fornix variables are measurable brain factors that precede the earliest clinically relevant deterioration of cognitive function among cognitively normal elderly individuals,” Fletcher said.

The research is published online today in JAMA Neurology.

Hippocampal atrophy occurs in the later stages of cognitive decline and is one of the most studied changes associated with the Alzheimer’s disease process. However, changes to the fornix and other regions of the brain structurally connected to the hippocampus have not been as closely examined. The study found that degeneration of the fornix in relation to cognition was detectable even earlier than changes in the hippocampus.

“Although hippocampal measures have been studied much more deeply in relation to cognitive decline, our direct comparison between fornix and hippocampus measures suggests that fornix properties have a superior ability to identify incipient cognitive decline among healthy individuals,” Fletcher said.

The study was conducted over five years in a group of 102 diverse, cognitively normal people with an average age of 73 who were recruited through community outreach at the Alzheimer’s Disease Center. The researchers conducted magnetic resonance imaging (MRI) studies of the participants’ brains that described their volumes and integrity. A different type of MRI was used to determine the integrity of the myelin, the fatty coating that sheaths and protects the axons. The axons are analogous to the copper wiring of the brain’s circuitry and the myelin is like the wiring’s plastic insulation.

Either one of those things being lost will “degrade the signal transmission” in the brain, Fletcher said.

The researchers also conducted psychological tests and cognitive evaluations of the study participants to gauge their level of cognitive functioning. The participants returned for updated MRIs and cognitive testing at approximately one-year intervals. At the outset, none of the study participants exhibited symptoms of cognitive decline. Over time about 20 percent began to show symptoms that led to diagnoses with either mild cognitive impairment (MCI) and, in a minority of cases, Alzheimer’s disease.

“We found that if you looked at various brain factors there was one — and only one — that seemed to be predictive of whether a person would have cognitive decline, and that was the degradation of the fornix,” Fletcher said.

The study measured two relevant fornix characteristics predicting future cognitive impairment — low fornix white matter volume and reduced axonal integrity. Each of these was stronger than any other brain factor in models predicting cognitive loss, Fletcher said. 

He said that routine MRI examination of the fornix could conceivably be used clinically in the future as a predictor of abnormal cognitive decline.

“Our findings suggest that if your fornix volume or integrity is within a certain range you’re at an increased risk of cognitive impairment down the road. But developing the use of the fornix as a predictor in a clinical setting will take some time, in the same way that it took time for evaluation of cholesterol levels to be used to predict future heart disease,” he said.

Fletcher also said that the finding may mark a paradigm shift toward evaluation of the brain’s white matter, rather than its gray matter, as among the very earliest indicators of developing cognitive loss. There is currently a strong research focus on understanding brain processes that lead eventually to Alzheimer’s disease. He said the current finding could fill in one piece of the picture and motivate new directions in research to understand why and how fornix and other white matter change is such an important harbinger of cognitive impairment. 

“The key importance of this finding is that it suggests that white matter tract measures may prove to be promising candidate biomarkers for predicting incipient cognitive decline among cognitively normal individuals in a clinical setting, possibly more so than gray matter measures,” he said.

(Source: ucdmc.ucdavis.edu)

Today’s primary tool for diagnosing Parkinson’s disease is the diagnostic ability of the physician, who can generally identify the clinical symptoms only when the disease is at a relatively advanced stage. A new joint study by researchers at the University of Haifa and Rambam Hospital that compared the handwriting of 40 sick and healthy subjects suggests an innovative and noninvasive method of diagnosing Parkinson’s at a fairly early stage.

“Identifying the changes in handwriting could lead to an early diagnosis of the illness and neurological intervention at a critical moment,” explains Prof. Sara Rosenblum, of the University of Haifa’s Department of Occupational Therapy, who initiated the study.

The methods for diagnosing Parkinson’s today are a physician evaluation or a test called SPECT, which uses radioactive material to image the brain. The latter, however, is no more effective in diagnosing the illness than an expert doctor and it exposes the patient to unnecessary radiation.

Studies from recent years show that there are unique and distinctive differences between the handwriting of patients with Parkinson’s disease and that of healthy people. However, most studies that to date have focused on handwriting focused on motor skills (such as the drawing of spirals) and not on writing that involves cognitive abilities, such as signing a check, copying addresses, etc.

According to Prof. Rosenblum, Parkinson’s patients report feeling a change in their cognitive abilities before detecting a change in their motor abilities and therefore a test of cognitive impairment like the one performed in this study could attest to the presence of the disease and offer a way to diagnose it earlier.

This research was conducted in cooperation with Dr. Ilana Schlesinger, head of the Center for Movement Disorders and Parkinson’s Disease at Haifa’s Rambam Medical Center and occupational therapists working in the hospital. In the study, the researchers asked the subjects to write their names and gave them addresses to copy, two everyday tasks that require cognitive abilities. Participants were 40 adults with at least 12 years of schooling, half healthy and half known to be in the early stages of Parkinson’s disease (before obvious motor signs are visible).

The writing was done on a regular piece of paper that was placed on electronic tablet, using a special pen with pressure-sensitive sensors operated by the pen when it hit the writing surface. A computerized analysis of the results compared a number of parameters: writing form (length, width and height of the letters), time required, and the pressure exerted on the surface while performing the assignment.

Analysis of the results showed significant differences between the patients and the healthy group, and all subjects, except one, had their status correctly diagnosed (97.5% accuracy). The Parkinson’s disease patients wrote smaller letters (“micrograph”), exerted less pressure on the writing surface, and took more time to complete the task. According to Prof. Rosenblum a particularly noticeable difference was the length of time the pen was in the air between the writing of each letter and each word.

“This finding is particularly important because while the patient holds the pen in the air, his mind is planning his next action in the writing process, and the need for more time reflects the subject’s reduced cognitive ability. Changes in handwriting can occur years before a clinical diagnosis and therefore can be an early signal of the approaching disease,” Prof. Rosenblum said.

According to Dr. Schlesinger, validating these findings in a broader study would allow this method to be used for a preliminary diagnosis of the disease in a safe and non-invasive fashion. “This study is a breakthrough toward an objective diagnosis of the disease,” said Dr. Schlesinger, adding, “Publication of the study in the journal of the European Neurological Society aroused great interest at the International Congress of Parkinson’s Disease and Movement held last week in Sydney, Australia.”

The researchers note that this diagnostic method has the added benefit of reducing the load on the health system, because the test can be performed by a professional other than a doctor. After the results are in, patients can be referred to a doctor for further treatment and testing if necessary. The researchers are currently using the method in a new experiment, in which they use handwriting analysis to evaluate the degree of Parkinson’s patients’ improved functioning after they have brain pacemakers implanted.

(Source: newswise.com)

Rodent research suggests feasibility of restoring neuron function

Research from the School of Medicine at The University of Texas Health Science Center at San Antonio suggests the exciting possibility of using cell transplants to treat schizophrenia.

Cells called “interneurons” inhibit activity within brain regions, but this braking or governing function is impaired in schizophrenia. Consequently, a group of nerve cells called the dopamine system go into overdrive. Different branches of the dopamine system are involved in cognition, movement and emotions.

“Since these cells are not functioning properly, our idea is to replace them,” said study senior author Daniel Lodge, Ph.D., assistant professor of pharmacology in the School of Medicine.

Transplant restored normal function

Dr. Lodge and lead author Stephanie Perez, graduate student in his laboratory, biopsied tissue from rat fetuses, isolated cells from the tissue and injected the cells into a brain center called the hippocampus. This center regulates the dopamine system and plays a role in learning, memory and executive functions such as decision making. Rats treated with the transplanted cells have restored hippocampal and dopamine function.

Stem cells are able to become different types of cells, and in this case interneurons were selected. “We put in a lot of cells and not all survived, but a significant portion did and restored hippocampal and dopamine function back to normal,” Dr. Lodge said.

‘You can essentially fix the problem’

Unlike traditional approaches to treating schizophrenia, such as medications and deep-brain stimulation, transplantation of interneurons potentially can produce a permanent solution. “You can essentially fix the problem,” Dr. Lodge said. “Ultimately, if this is translated to humans, we want to reprogram a patient’s own cells and use them.”

After meeting with other students, Perez brought the research idea to Dr. Lodge. “The students have journal club, and somebody had done a similar experiment to restore motor deficits and had good results,” Perez said. “We thought, why can’t we use it for schizophrenia and have good results, and so far we have.”

The study is in Molecular Psychiatry.

(Source: uthscsa.edu)

Subarachnoid haemorrhage (SAH) is one of the most devastating cerebrovascular catastrophes causing death in 40 to 50% of the cases. The most common cause of SAH is a rupture of an intracranial aneurysm. If the aneurysm is found, it can be treated before the possible rupture. However, some intracranial aneurysms will never rupture – the problem is that the doctors don’t know which aneurysms will and which will not. So, they don’t know which patients should be treated and who can safely be left untreated.

(Image: This picture shows: A middle cerebral artery bifurcation aneurysm. Credit: Miikka Korja)

A long-term, population-based Finnish study on SAH, which is based on the FINRISK health examination surveys, and published in PLOS ONE on 9th September, shows that the risk of SAH depends strongly on the combination of certain risk factors. The SAH incidence was shown to vary from 8 up to 171 per 100 000 person-years, depending on whether people had multiple risk factors for SAH – such as smoking, hypertension and female sex – or not.

Such an extreme risk factor -dependent variation in the incidence of any cardiovascular disease is exceptional, and may have significant clinical implications, says one of the main authors, Associate Professor Miikka Korja from the Helsinki University Central Hospital and Australian School of Advanced Medicine.

If smoking women with high systolic blood pressure values have 20 times higher rate of these brain bleeds than never-smoking men with low blood pressure values, it may very well be that these women diagnosed with unruptured intracranial aneurysms should be treated. On the other hand, never-smoking men with low blood pressure values and intracranial aneurysms may not need to be treated at all.

In this largest SAH risk factor study ever, the study group also identified three new risk factors for SAH: previous myocardial infarction, history of stroke in mother, and elevated cholesterol levels in men. The results revise the understanding of the epidemiology of SAH and indicate that the risk factors for SAH appear to be similar to those for other cardiovascular diseases.

We have previously shown that lifestyle risk factors affect significantly the life expectancy of SAH survivors, and now we have shown that the same risk factors also affect dramatically the risk of SAH itself. Thus, it appears quite clear that especially smoking cessation and hypertension treatment are important in preventing SAH and increasing life expectancy after SAH, clarifies one of the study group members, Academy Professor Jaakko Kaprio, from the University of Helsinki and National Institute for Health and Welfare, referring to their previous publication on cause-specific mortality on SAH survivors (Korja et al., Neurology, 2013).

The study group members have previously published also the largest twin study to date, confirming that heritability for SAH is very low (Korja et al., Stroke, 2010), and the first study on the incidence of SAH in type 1 diabetes, showing that the rate of non-aneurysmal SAHs in type 1 diabetes is unusually high (Korja et al., Diabetes Care, 2013).

Many of the previous studies on the epidemiology of SAH have relied on retrospective and single-center databases, which are unfortunately not very reliable data sources. Due to the unique health care system and common academic interest among doctors in Nordic countries, it has been possible to conduct high-quality and unbiased studies on SAH. We hope that our studies truly help doctors and patients, and are not only of interest in coffee tables on university campuses, says neurosurgeon Korja, and rushes to continue his working day in the operation room in Macquarie University Hospital, Sydney, which is one of his current appointments.

(Source: eurekalert.org)

Ever tried beetroot custard? Probably not, but your brain can imagine how it might taste by reactivating old memories in a new pattern.

Helen Barron and her colleagues at University College London and Oxford University wondered if our brains combine existing memories to help us decide whether to try something new.

So the team used an fMRI scanner to look at the brains of 19 volunteers who were asked to remember specific foods they had tried.

Each volunteer was then given a menu of 13 unusual food combinations – including beetroot custard, tea jelly, and coffee yoghurt – and asked to imagine how good or bad they would taste, and whether or not they would eat them.

"Tea jelly was popular," says Barron. "Beetroot custard not so much."

When each volunteer imagined a new combination, they showed brain activity associated with each of the known ingredients at the same time. It is the first evidence to suggest that we use memory combination to make decisions, says Barron.

(Source: newscientist.com)

A consortium of scientists from 20 countries, including researchers from The University of Western Australia, has made a major breakthrough in understanding the genetic basis of the debilitating disorder, schizophrenia.

More than 175 scientists from 99 institutions across Europe, the United States of America and Australia contributed to a genome-wide association analysis which identified 13 new risk loci for schizophrenia.

In an article published in the journal, Nature Genetics, the study authors write that the results provide deeper insight into the genetic architecture of schizophrenia than ever before achieved, and provide a pathway to further research.

"For the first time, there is a clear path to increased knowledge of the etiology of schizophrenia through the application of standard, off-the-shelf genomic technologies for elucidating the effects of common variation," the authors wrote.

Schizophrenia is a complex mental disorder which affects about one per cent of people over their lifetime, leading to prolonged or recurrent episodes that impair severely social functioning and quality of life.

In terms of the ‘global burden of disease and disability’ index, developed by the World Health Organization, it ranks among the top 10 disorders, along with cancer, heart disease, diabetes and other non-communicable diseases.

Winthrop Professor Assen Jablensky, director of UWA’s Centre for Clinical Research in Neuropsychiatry (CCRN) at Graylands Hospital, and Professor Luba Kalaydjieva, of the UWA-affiliated Western Australian Institute for Medical Research (WAIMR), led the UWA research team which took part in the study.

Professor Jablensky said that while a strong genetic component in the causation of schizophrenia had been well established, the role of specific genes and the mechanisms of their regulation remained largely unknown.

"Until recently, results of genetic linkage and association studies could explain only a small fraction of the estimated heritability of the disorder and of its ‘genetic architecture’," Professor Jablensky said.

However recent technological advances, enabling efficient coverage of the entire human genome with millions of single nucleotide polymorphisms (SNPs) as genetic markers, had given rise to a new generation of genome-wide association studies (GWAS), which trace the DNA differences between people affected with the disease and healthy control individuals.

"Since the effects of individual SNPs are quite tiny, their reliable measurement requires very large samples of adequately diagnosed patients and controls," Professor Jablensky said.

"This recent study reports on a major breakthrough in the understanding of the genetic basis of schizophrenia, achieved through meta-analysis of GWAS datasets contributed by a large international Psychiatric Genomics Consortium (PGC) - which includes the UWA research team."

A WA case-control sample consisting of 893 schizophrenia patients and healthy controls was part of a collection of 21,246 schizophrenia cases and 38,072 controls from 19 research centres and consortia across Europe, Australia and the USA.

The study found that a total of 8300 SNPs contribute to the risk for schizophrenia and account for at least 32 per cent of the variance in liability.

"A particularly important result of this study is that many of these SNPs are located on a molecular pathway involved in neuronal calcium signalling, which suggests a novel pathogenetic link in the causation of schizophrenia and possibly other psychotic disorders," Professor Jablensky said.

He said ongoing and future studies by the UWA research team would aim to further refine the genetic analyses of the WA schizophrenia study (which at present includes 1259 persons), and to test neurobiological hypotheses about the treatment responses of genetically defined subsets of patients. 

(Source: news.uwa.edu.au)