Posts tagged science

In a long-term, large-scale population-based study of individuals aged 55 years or older in the general population researchers found that those diagnosed with mild cognitive impairment (MCI) had a four-fold increased risk of developing dementia or Alzheimer’s disease (AD) compared to cognitively healthy individuals. Several risk factors including older age, positive APOE-ɛ4 status, low total cholesterol levels, and stroke, as well as specific MRI findings were associated with an increased risk of developing MCI. The results are published in a supplement to the Journal of Alzheimer’s Disease.

“Mild cognitive impairment has been identified as the transitional stage between normal aging and dementia,” comments M. Arfan Ikram, MD, PhD, a neuroepidemiologist at Erasmus MC University Medical Center (Rotterdam). “Identifying persons at a higher risk of dementia could postpone or even prevent dementia by timely targeting modifiable risk factors.”

Unlike a clinical trial, the Rotterdam study is an observational cohort study focusing on the general population, instead of persons referred to a memory clinic. The Rotterdam study began in 1990, when almost 8,000 inhabitants of Rotterdam aged 55 years or older agreed to participate in the study. Ten years later, another 3,000 individuals were added. Participants undergo home interviews and examinations every four years.

“This important prospective study adds to the accumulating evidence that strokes, presumably related to so called ‘vascular’ risk factors, also contribute to the appearance of dementia in Alzheimer’s disease. This leads to the conclusion that starting at midlife people should minimize those risk factors. The recent results of the Finish FINGER study corroborate this idea. It should be remembered that delaying the onset of dementia by five years will reduce the prevalence of the disease by half. And of course, since there is no cure for AD, prevention is the best approach at present,” explains Professor Emeritus Amos D Korczyn, Tel Aviv University, Ramat Aviv, Israel, and Guest Editor of the Supplement.

To be diagnosed with MCI in the study, individuals were required to meet three criteria: a self-reported awareness of having problems with memory or everyday functioning; deficits detected on a battery of cognitive tests; and no evidence of dementia. They were categorized into those with memory problems (amnestic MCI) and those with normal memory (non-amnestic MCI).

Of 4,198 persons found to be eligible for the study, almost 10% were diagnosed with MCI. Of these, 163 had amnestic MCI and 254 had non-amnestic MCI.

The risk of dementia was especially high for people with amnestic MCI. Similar results were observed regarding the risk for Alzheimer’s disease. Those with MCI also faced a somewhat higher risk of death. 

The research team investigated possible determinants of MCI, considering factors such as age, APOE-ɛ status, waist circumference, hypertension, diabetes mellitus, total and HDL-cholesterol levels, smoking, and stroke. Only older age, being an APOE-ɛ4 carrier, low total cholesterol levels, and stroke at baseline were associated with developing MCI. Having the APOE-ɛ4 genotype and smoking were related only to amnestic MCI.

When the investigators analysed MRI studies of the brain, they found that participants with MCI, particularly those with non-amnestic MCI, had larger white matter lesion volumes and worse microstructural integrity of normal-appearing white matter compared to controls. They were also three-times more likely than controls to have lacunes (3 to 15 mm cerebrospinal fluid (CSF)-filled cavities in the basal ganglia or white matter, frequently observed when imaging older people). MCI was not associated with total brain volume, hippocampal volume, or cerebral microbleeds.

“Our results suggest that accumulating vascular damage plays a role in both amnestic and non-amnestic MCI,” says Dr. Ikram. “We propose that timely targeting of modifiable vascular risk factors might contribute to the prevention of MCI and dementia.”

Reference:

Determinants, MRI Correlates, and Prognosis of Mild Cognitive Impairment: The Rotterdam Study. Renée F.A.G. de Bruijn, Saloua Akoudad, Lotte G.M. Cremers, Albert Hofman, Wiro J. Niessen, Aad van der Lugt, Peter J. Koudstaal, Meike W. Vernooij, M. Arfan Ikram. Journal of Alzheimer’s Disease, Volume 42/Supplement 3 (August 2014): 2013 International Congress on Vascular Dementia (Guest Editor: Amos D. Korczyn)

(Source: iospress.nl)

The team studied elderly Americans who took part in the Cardiovascular Health Study. They discovered that adults in the study who were moderately deficient in vitamin D had a 53 per cent increased risk of developing dementia of any kind, and the risk increased to 125 per cent in those who were severely deficient.

Similar results were recorded for Alzheimer’s disease, with the moderately deficient group 69 per cent more likely to develop this type of dementia, jumping to a 122 per cent increased risk for those severely deficient.

The study was part-funded by the Alzheimer’s Association, and is published in August 6 2014 online issue of Neurology, the medical journal of the American Academy of Neurology. It looked at 1,658 adults aged 65 and over, who were able to walk unaided and were free from dementia, cardiovascular disease and stroke at the start of the study. The participants were then followed for six years to investigate who went on to develop Alzheimer’s disease and other forms of dementia.

Dr Llewellyn said: “We expected to find an association between low Vitamin D levels and the risk of dementia and Alzheimer’s disease, but the results were surprising – we actually found that the association was twice as strong as we anticipated.

“Clinical trials are now needed to establish whether eating foods such as oily fish or taking vitamin D supplements can delay or even prevent the onset of Alzheimer’s disease and dementia. We need to be cautious at this early stage and our latest results do not demonstrate that low vitamin D levels cause dementia. That said, our findings are very encouraging, and even if a small number of people could benefit, this would have enormous public health implications given the devastating and costly nature of dementia.”

Research collaborators included experts from Angers University Hospital, Florida International University, Columbia University, the University of Washington, the University of Pittsburgh and the University of Michigan. The study was supported by the Alzheimer’s Association, the Mary Kinross Charitable Trust, the James Tudor Foundation, the Halpin Trust, the Age Related Diseases and Health Trust, the Norman Family Charitable Trust, and the National Institute for Health Research Collaboration for Leadership in Applied Research and Care South West Peninsula (NIHR PenCLAHRC).

Dementia is one of the greatest challenges of our time, with 44 million cases worldwide – a number expected to triple by 2050 as a result of rapid population ageing. A billion people worldwide are thought to have low vitamin D levels and many older adults may experience poorer health as a result.

The research is the first large study to investigate the relationship between vitamin D and dementia risk where the diagnosis was made by an expert multidisciplinary team, using a wide range of information including neuroimaging. Previous research established that people with low vitamin D levels are more likely to go on to experience cognitive problems, but this study confirms that this translates into a substantial increase in the risk of Alzheimer’s disease and dementia.

Vitamin D comes from three main sources – exposure of skin to sunlight, foods such as oily fish, and supplements. Older people’s skin can be less efficient at converting sunlight into Vitamin D, making them more likely to be deficient and reliant on other sources. In many countries the amount of UVB radiation in winter is too low to allow vitamin D production.

The study also found evidence that there is a threshold level of Vitamin D circulating in the bloodstream below which the risk of developing dementia and Alzheimer’s disease increases.  The team had previously hypothesized that this might lie in the region of 25-50 nmol/L, and their new findings confirm that vitamin D levels above 50 nmol/L are most strongly associated with good brain health.

Commenting on the study, Dr Doug Brown, Director of Research and Development at Alzheimer’s Society said: “Shedding light on risk factors for dementia is one of the most important tasks facing today’s health researchers. While earlier studies have suggested that a lack of the sunshine vitamin is linked to an increased risk of Alzheimer’s disease, this study found that people with very low vitamin D levels were more than twice as likely to develop any kind of dementia.

“During this hottest of summers, hitting the beach for just 15 minutes of sunshine is enough to boost your vitamin D levels. However, we’re not quite ready to say that sunlight or vitamin D supplements will reduce your risk of dementia. Large scale clinical trials are needed to determine whether increasing vitamin D levels in those with deficiencies can help prevent the dementia from developing.”

(Source: exeter.ac.uk)

A Japanese research group led by Prof Norihiro Sadato, a professor of the National Institute for Physiological Sciences (NIPS), National Institutes of Natural Sciences (NINS), has found that people with autism spectrum disorders (ASD) have decreased activity in an area in the brain critical for understanding if his/her movement was imitated by others. These results will be published in Neuroscience Research.

The research group of Norihiro Sadato, a professor of NIPS, Hirotaka Kosaka, a specially-assigned associate professor of the University of Fukui, and Toshio Munesue, a professor of Kanazawa University measured brain activity by functional magnetic resonance imaging (fMRI) when one’s movement was imitated by others. The group studied brain activity when a subject saw his/her finger movement imitated or not imitated by others. Normal subjects have increased activity in the extrastriate body area (EBA) when they are imitated compared to when they are not being imitated. The EBA is a region in the visual cortex for visual processing that responds powerfully during the perception of human body parts. On the other hand, because this kind of activity in the EBA of subjects with ASD was not observed, it shows that the EBA of subjects with ASD is not working properly when imitated.

Persons with ASD are known to have difficulty in interpersonal communication and have trouble noticing that their movement was imitated. Behavioral intervention research to alleviate ASD is proceeding and indicates that training utilizing imitation is useful. The result of the above research not only provided clues to ASD, but also can be used in the evaluation of behavioral intervention to alleviate the disorder.

(Source: eurekalert.org)

(Source: med.stanford.edu)

In some women abnormally high levels of a common and pervasive chemical may lead to adverse effects in their offspring. The study, published recently in the Journal of Clinical Endocrinology & Metabolism, is the first of its kind to shed light on the possible harmful side effects of perchlorate in mothers and their children.

Using data from the Controlled Antenatal Thyroid Study (CATS) cohort, researchers at Boston University School of Medicine (BUSM) and Cardiff University studied the effect of perchlorate, an environmental contaminant found in many foods and in some drinking water supplies, and its effects on children born to mothers with above average levels of this substance in their system. They studied 487 mother-child pairs from women with underactive thyroid glands and in the 50 women with the highest levels of perchlorate in their body, their offspring had below average IQ levels when compared to other children.

"The reason people really care about perchlorate is because it is ubiquitous. It’s everywhere," said Elizabeth Pearce, MD, MSc, associate professor of medicine at BUSM. "Prior studies have already shown perchlorate, at low levels, can be found in each and every one of us."

Perchlorate is a compound known to affect the thyroid gland, an organ needed to help regulate hormone levels in humans. According to Pearce previous studies have attempted to implicate this anti-thyroid activity in pregnant mothers as a possible cause of hypothyroidism, or an underactive thyroid gland. Hypothyroidism in newborns and children can lead to an array of unwelcome side effects, including below average intelligence.

(Source: eurekalert.org)

Research at the University of Reading has provided a new understanding of how our brain processes information to change how we see the world.

Using a simple computer game, akin to a 3D version of the 80s game Pong, the researchers examined how the brain recalibrates its perception of slant in order to bounce a moving ball through a target hoop.

They found that the brain uses an internal simulation of the laws of physics to change its perception of slant in order to ‘score’ consistently.

The findings provide a unique insight into why humans are such an adaptable and skillful species. With the development of effective autonomous robots, engineers are starting to look at how humans’ sensory systems effortlessly achieve what is currently impossible for robotic systems.

The study, funded by the Engineering and Physical Sciences Research Council and the Wellcome Trust, saw participants play a 3D game where they had to adjust the slant of a surface so that a moving ball bounced off it and through a target hoop.

Part way through the game, without telling the participants, researchers altered the bounce of the ball so that the surface behaved differently to the slant signalled by visual cues. 

When faced with the altered bounce, participants changed their behaviour to continue scoring points. At the same time, their brain recalibrated their perception of slant - simulating the laws of physics to actually change how the slant looked. In a separate group, making the ball spin eliminated this recalibration.

Dr. Peter Scarfe from the School of Psychology and Clinical Language Sciences, who conducted the study with colleague Prof. Andrew Glennerster, said: “We take for granted our amazing ‘adaptability’ which allows us to enjoy such past-times as DIY or playing ball sports. However, little is known about the brain mechanisms that enable us to do these activities. Our research shows how our brains appear to have an intimate understanding of the laws of physics. In addition to aiding skillful action, this can change how we perceive the world around us.”

The researchers say understanding the basic mechanisms that allow the brain to calibrate sensory information will prove vital in the design of future autonomous robots.

Dr. Scarfe continued: “The human brain exhibits expert skill in making predictions about how the world behaves. For example, a child can bounce a ball off a wall and understand how spinning the ball alters its bounce. However, many of the fine motor skills of a young child are currently way beyond the capability of modern robots. Understanding how sensory systems adapt to feedback about the consequences of actions is likely to be key in solving this problem.”

Humans Use Predictive Kinematic Models to Calibrate Visual Cues to Three-Dimensional Surface Slant is published in the Journal of Neuroscience

(Source: reading.ac.uk)

Researchers at Yale School of Medicine have discovered a new drug compound that reverses the brain deficits of Alzheimer’s disease in an animal model. Their findings are published in the Aug. 5 issue of the journal PLoS Biology.

The compound, TC-2153, inhibits the negative effects of a protein called STtriatal-Enriched tyrosine Phosphatase (STEP), which is key to regulating learning and memory. These cognitive functions are impaired in Alzheimer’s.

"Decreasing STEP levels reversed the effects of Alzheimer’s disease in mice," said lead author Paul Lombroso, M.D., professor in the Yale Child Study Center and in the Departments of Neurobiology and Psychiatry at Yale School of Medicine.

Lombroso and co-authors studied thousands of small molecules, searching for those that would inhibit STEP activity. Once identified, those STEP-inhibiting compounds were tested in brain cells to examine how effectively they could halt the effects of STEP. They examined the most promising compound in a mouse model of Alzheimer’s disease, and found a reversal of deficits in several cognitive exercises that gauged the animals’ ability to remember previously seen objects.

High levels of STEP proteins keep synapses in the brain from strengthening. Synaptic strengthening is a process that is required for people to turn short-term memories into long-term memories. When STEP is elevated in the brain, it depletes receptors from synaptic sites, and inactivates other proteins that are necessary for proper cognitive function. This disruption can result in Alzheimer’s disease or a number of neuropsychiatric and neurodegenerative disorders, all marked by cognitive deficits.

"The small molecule inhibitor is the result of a five-year collaborative effort to search for STEP inhibitors," said Lombroso. "A single dose of the drug results in improved cognitive function in mice. Animals treated with TC compound were indistinguishable from a control group in several cognitive tasks."

The team is currently testing the TC compound in other animals with cognitive defects, including rats and non-human primates. “These studies will determine whether the compound can improve cognitive deficits in other animal models,” said Lombroso. “Successful results will bring us a step closer to testing a drug that improves cognition in humans.”

(Source: eurekalert.org)