Posts Tagged ‘dementia’

The majority of the cells in the brain are no neurons, but Glia (from “glue”) cells, that support the structure and function of the brain. Astrocytes (“start cells”) are star-shaped glial cells providing many supportive functions for the neurons surrounding them, such as the provision of nutrients and the regulation of their chemical environment. Newer studies showed that astrocytes also monitor and modulate neuronal activity. For example, these studies have shown that astrocytes are necessary for the ability of neurons to change the strength of the connections between them, the process underlying learning and memory, and indeed astrocytes are also necessary for normal cognitive function. However, it is still unknown whether astrocytic activity is only necessary, or is it may also be sufficient to induce synaptic potentiation and enhance cognitive performance.

In a new study published in Cell, two graduate students, Adar Adamsky and Adi Kol, from Inbal Goshen’s lab, employed chemogenetic and optogenetic tools that allow specific activation of astrocytes in behaving mice, to explore their role in synaptic activity and memory performance. They found that astrocytic activation in the hippocampus, a brain region that plays an important role in memory acquisition and consolidation, potentiated the synaptic connections in this region, measured in brain slices. Moreover, in the intact brain, astrocytic activation enhanced hippocampal neuronal activity in a task-dependent way: i.e. only during when it was combined with memory acquisition, but not when mice were at their home cage with no meaningful stimuli. The ability of astrocytes to increase neuronal activity during memory acquisition had a significant effect on cognitive function: Specifically, astrocytic activation during learning resulted in enhanced memory in two memory tests. In contrast, direct neuronal activation in the hippocampus induced a non-selective increase in activity (during learning or in the home cage), and thus resulted in drastic memory impairment.

The results suggest that the memory enhancement induced by astrocytic activation during learning is not simply a result of a general increase in hippocampal neuronal activity. Rather, the astrocytes, which sense and respond to changes in the surrounding neuronal activity, can detect and specifically enhance only the neuronal activity involved in learning, without affecting the general activity. This may explain why general astrocytic activation improves memory performance, whereas a similar activation of neurons impairs it.

Memory is not a binary process (remember/don’t remember); the strength of a memory can vary greatly, either for the same memory or between different memories. Here, we show that activating astrocytes in mice with intact cognition improves their memory performance. This finding has important clinical implications for cognitive augmentation treatments. Furthermore, the ability of astrocytes to strengthen neuronal communication and improve memory performance supports the claim that astrocytes are able to take an active part in the neuronal processes underlying cognitive function. This perspective expands the definition of the role of astrocytes, from passive support cells to active cells that can modulate neural activity and thus shape behavior.

Link: https://www.cell.com/cell/pdf/S0092-8674(18)30575-0.pdf

https://elsc.huji.ac.il/content/article-month-june-2018-goshens-lab

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Neuroscientists at Indiana University have reported the first evidence that non-human animals can mentally replay past events from memory. The discovery could help advance the development of new drugs to treat Alzheimer’s disease.

The study, led by IU professor Jonathon Crystal, appears today in the journal Current Biology.

“The reason we’re interested in animal memory isn’t only to understand animals, but rather to develop new models of memory that match up with the types of memory impaired in human diseases such as Alzheimer’s disease,” said Crystal, a professor in the IU Bloomington College of Arts and Sciences’ Department of Psychological and Brain Sciences and director of the IU Bloomington Program in Neuroscience.

Under the current paradigm, Crystal said most preclinical studies on potential new Alzheimer’s drugs examine how these compounds affect spatial memory, one of the easiest types of memory to assess in animals. But spatial memory is not the type of memory whose loss causes the most debilitating effects of Alzheimer’s disease.

“If your grandmother is suffering from Alzheimer’s, one of the most heartbreaking aspects of the disease is that she can’t remember what you told her about what’s happening in your life the last time you saw her,” said Danielle Panoz-Brown, an IU Ph.D. student who is the first author on the study. “We’re interested in episodic memory — and episodic memory replay — because it declines in Alzheimer’s disease, and in aging in general.”

Episodic memory is the ability to remember specific events. For example, if a person loses their car keys, they might try to recall every single step — or “episode” — in their trip from the car to their current location. The ability to replay these events in order is known as “episodic memory replay.” People wouldn’t be able to make sense of most scenarios if they couldn’t remember the order in which they occurred, Crystal said.

To assess animals’ ability to replay past events from memory, Crystal’s lab spent nearly a year working with 13 rats, which they trained to memorize a list of up to 12 different odors. The rats were placed inside an “arena” with different odors and rewarded when they identified the second-to-last odor or fourth-to-last odor in the list.

The team changed the number of odors in the list before each test to confirm the odors were identified based upon their position in the list, not by scent alone, proving the animals were relying on their ability to recall the whole list in order. Arenas with different patterns were used to communicate to the rats which of the two options was sought.

After their training, Crystal said, the animals successfully completed their task about 87 percent of the time across all trials. The results are strong evidence the animals were employing episodic memory replay.

Additional experiments confirmed the rats’ memories were long-lasting and resistant to “interference” from other memories, both hallmarks of episodic memory. They also ran tests that temporarily suppressed activity in the hippocampus — the site of episodic memory — to confirm the rats were using this part of their brain to perform their tasks.

Crystal said the need to find reliable ways to test episodic memory replay in rats is urgent since new genetic tools are enabling scientists to create rats with neurological conditions similar to Alzheimer’s disease. Until recently, only mice were available with the genetic modifications needed to study the effect of new drugs on these symptoms.

“We’re really trying push the boundaries of animal models of memory to something that’s increasingly similar to how these memories work in people,” he said. “If we want to eliminate Alzheimer’s disease, we really need to make sure we’re trying to protect the right type of memory.”

https://news.iu.edu/stories/2018/05/iub/releases/10-scientists-find-first-evidence-animals-can-mentally-replay-past-events.html

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Researchers reported on Monday in the journal JAMA Neurology that dementia was a possible complication following concussion even if the patient did not lose consciousness.

Scientists from the University of California, San Francisco (UCSF) tracked more than one-third of a million American veterans, and found that the likelihood of dementia more than doubled following concussion.

After adjusting for age, sex, race, education and other health conditions, they found that concussion without loss of consciousness led to 2.36 times the risk for dementia.

According to the study, these risks were slightly elevated for those in the loss-of-consciousness bracket (2.51 times) and were nearly four times higher (3.77 times) for those with the more serious moderate-to-severe traumatic brain injury.

In the total of 357,558 participants, whose average age was 49, half had been diagnosed with traumatic brain injury, of which 54 percent had concussion. The study followed participants for an average of 4.2 years, and 91 percent were male and 72 percent were white.

“There are several mechanisms that may explain the association between traumatic brain injury and dementia,” said the study’s senior author Kristine Yaffe, professor with the UCSF departments of neurology, psychiatry, and epidemiology and biostatistics.

“There’s something about trauma that may hasten the development of neurodegenerative conditions. One theory is that brain injury induces or accelerates the accumulation of abnormal proteins that lead to neuronal death associated with conditions like Alzheimer’s disease,” said Yaffe.

“It’s also possible that trauma leaves the brain more vulnerable to other injuries or aging processes,” said Yaffe, “but we need more work in this area.”

http://www.xinhuanet.com/english/2018-05/08/c_137162226.htm


Psychological sciences doctoral student Marci Horn (left) conducts a name-face memory test as part of a study at the Center for Vital Longevity.

New research from the Center for Vital Longevity (CVL) at The University of Texas at Dallas suggests that subjective complaints about poor memory performance, especially in people over 60, could be a useful early marker for the onset of mild cognitive decline, which sometimes foreshadows Alzheimer’s disease.

Subjective memory is a person’s unscientific self-evaluation of how good his or her memory is, and whether, in that person’s opinion, there has been any worsening of memory through age. While some changes may be undetectable to others and are often too subtle to register on cognitive tests, the person subjectively believes that memory is slipping.

Published recently in Psychology and Aging, the research from Dr. Karen Rodrigue’s lab at CVL examined subjective memory complaints in nearly 200 healthy adults, ages 20 to 94. Previous studies suggest that subjective memory complaints are not necessarily indicative of cognitive decline, and may stem from underlying conditions such as anxiety and depression, which have been shown to impede memory.

The current study measured mood and screened out depressed individuals. Researchers also measured participants for known risk factors for memory loss and Alzheimer’s, such as higher levels of beta-amyloid in the brain and the presence of a gene variant called ApoE4. These factors were taken into account to examine whether subjective memory alone was a reliable correlate of actual memory ability.

The study focused on associative memory — for example, remembering word pairs and name-face pairs. This type of memory is particularly sensitive to age-related decline, and the most common complaint of aging individuals.

The study found that a person’s intuitive or intrinsic assessment of his or her own memory was actually a reliable predictor of performance on the laboratory memory assessment. This result was particularly true for individuals with genetic risk for memory loss.

“Our findings show that subjective memory can be a reliable indicator of memory performance, even in cognitively healthy adults,” said psychological sciences doctoral student Marci Horn, the lead author of the study. “The same people who self-report memory problems may also have other risk factors associated with increased risk of Alzheimer’s disease.”

The researchers also found that men who had higher amyloid levels reported the most subjective memory complaints in the study. Previous studies had not uncovered a sex-specific relationship, nor did they account for the genetic and amyloid risk factors in these associations, the researchers said.

The strongest correlation of subjective memory complaints with actual cognitive performance was in study participants older than 60, when people are generally at greater risk for Alzheimer’s disease.

“It seems that awareness of memory changes may be a reliable indicator of one’s current memory ability, and may serve as another harbinger of future loss, as this relationship was strongest in those with known risk factors for Alzheimer’s disease, namely ApoE4 genotype and beta-amyloid burden in the brain,” said Rodrigue, the senior author of the study and assistant professor in the School of Behavioral and Brain Sciences (BBS). “We are following these individuals over time to further test this idea.”

Dr. Kristen Kennedy, an assistant professor in BBS, also was an author of the study. The research was funded in part by grants from the National Institutes of Health.

https://www.utdallas.edu/news/2018/4/30-32929_Subjective-Memory-May-Play-Role-in-Signaling-Cogni_story-wide.html?WT.mc_id=NewsHomePageCenterColumn

Ever get chills listening to a particularly moving piece of music? You can thank the salience network of the brain for that emotional joint. Surprisingly, this region also remains an island of remembrance that is spared from the ravages of Alzheimer’s disease. Researchers at the University of Utah Health are looking to this region of the brain to develop music-based treatments to help alleviate anxiety in patients with dementia. Their research will appear in the April online issue of The Journal of Prevention of Alzheimer’s Disease.

“People with dementia are confronted by a world that is unfamiliar to them, which causes disorientation and anxiety” said Jeff Anderson, M.D., Ph.D., associate professor in Radiology at U of U Health and contributing author on the study.“We believe music will tap into the salience network of the brain that is still relatively functioning.”

Previous work demonstrated the effect of a personalized music program on mood for dementia patients. This study set out to examine a mechanism that activates the attentional network in the salience region of the brain. The results offer a new way to approach anxiety, depression and agitation in patients with dementia. Activation of neighboring regions of the brain may also offer opportunities to delay the continued decline caused by the disease.

For three weeks, the researchers helped participants select meaningful songs and trained the patient and caregiver on how to use a portable media player loaded with the self-selected collection of music.

“When you put headphones on dementia patients and play familiar music, they come alive,” said Jace King, a graduate student in the Brain Network Lab and first author on the paper. “Music is like an anchor, grounding the patient back in reality.”

Using a functional MRI, the researchers scanned the patients to image the regions of the brain that lit up when they listened to 20-second clips of music versus silence. The researchers played eight clips of music from the patient’s music collection, eight clips of the same music played in reverse and eight blocks of silence. The researchers compared the images from each scan.

The researchers found that music activates the brain, causing whole regions to communicate. By listening to the personal soundtrack, the visual network, the salience network, the executive network and the cerebellar and corticocerebellar network pairs all showed significantly higher functional connectivity.

“This is objective evidence from brain imaging that shows personally meaningful music is an alternative route for communicating with patients who have Alzheimer’s disease,” said Norman Foster, M.D., Director of the Center for Alzheimer’s Care at U of U Health and senior author on the paper.“Language and visual memory pathways are damaged early as the disease progresses, but personalized music programs can activate the brain, especially for patients who are losing contact with their environment.”

However, these results are by no means conclusive. The researchers note the small sample size (17 participants) for this study. In addition, the study only included a single imaging session for each patient. It is remains unclear whether the effects identified in this study persist beyond a brief period of stimulation or whether other areas of memory or mood are enhanced by changes in neural activation and connectivity for the long term.

“In our society, the diagnoses of dementia are snowballing and are taxing resources to the max,” Anderson said. “No one says playing music will be a cure for Alzheimer’s disease, but it might make the symptoms more manageable, decrease the cost of care and improve a patient’s quality of life.”

https://www.technologynetworks.com/neuroscience/news/music-activation-of-salience-network-could-alleviate-anxiety-in-alzheimers-disease-300268?utm_campaign=Newsletter_TN_BreakingScienceNews&utm_source=hs_email&utm_medium=email&utm_content=62522460&_hsenc=p2ANqtz-9ihWyFIxhX4_ZqRqTTeOrNwa0ZHtTKERWsL_8k0sb5boN7jUkYGkdh9HwUwTgNxQfBVCpLL2CkwNk4uJpbMDlvKJPNJw&_hsmi=62522460


The study simulated long-term consumption of three cups of coffee a day.

It is well known that memory problems are the hallmarks of Alzheimer’s disease. However, this dementia is also characterized by neuro-psychiatric symptoms, which may be strongly present already in the first stages of the disorder. Known as Behavioural and Psychological Symptoms of Dementia (BPSD), this array of symptoms — including anxiety, apathy, depression, hallucinations, paranoia and sundowning (or late-day confusion) — are manifested in different manners depending on the individual patient, and are considered the strongest source of distress for patients and caregivers.


Coffee and caffeine: good or bad for dementia?

Caffeine has recently been suggested as a strategy to prevent dementia, both in patients with Alzheimer’s disease and in normal ageing processes. This is due to its action in blocking molecules — adenosine receptors — which may cause dysfunctions and diseases in old age. However, there is some evidence that once cognitive and neuro-psychiatric symptoms develop, caffeine may exert opposite effects.

To investigate this further, researchers from Spain and Sweden conducted a study with normal ageing mice and familial Alzheimer’s models. The research, published in Frontiers in Pharmacology, was conducted from the onset of the disease up to more advanced stages, as well as in healthy age-matched mice.

“The mice develop Alzheimer’s disease in a very close manner to human patients with early-onset form of the disease,” explains first author Raquel Baeta-Corral, from Universitat Autònoma de Barcelona, Spain. “They not only exhibit the typical cognitive problems but also a number of BPSD-like symptoms. This makes them a valuable model to address whether the benefits of caffeine will be able to compensate its putative negative effects.”

“We had previously demonstrated the importance of the adenosine A1 receptor as the cause of some of caffeine’s adverse effects,” explains Dr. Björn Johansson, a researcher and physician at the Karolinska University Hospital, Sweden.

“In this study, we simulated a long oral treatment with a very low dose of caffeine (0.3 mg/mL) — equivalent to three cups of coffee a day for a human — to answer a question which is relevant for patients with Alzheimer’s, but also for the ageing population in general, and that in people would take years to be solved since we would need to wait until the patients were aged.”

Worsened Alzheimer’s symptoms outweigh cognition benefits

The results indicate that caffeine alters the behavior of healthy mice and worsens the neuropsychiatric symptoms of mice with Alzheimer’s disease. The researchers discovered significant effects in the majority of the study variables — and especially in relation to neophobia (a fear of everything new), anxiety-related behaviors, and emotional and cognitive flexibility.

In mice with Alzheimer’s disease, the increase in neophobia and anxiety-related behaviours exacerbates their BPSD-like profile. Learning and memory, strongly influenced by anxiety, got little benefit from caffeine.

“Our observations of adverse caffeine effects in an Alzheimer’s disease model, together with previous clinical observations, suggest that an exacerbation of BPSD-like symptoms may partly interfere with the beneficial cognitive effects of caffeine. These results are relevant when coffee-derived new potential treatments for dementia are to be devised and tested,” says Dr. Lydia Giménez-Llort, researcher from the INc-UAB Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, and lead researcher of the project.

The results of the study form part of the PhD thesis of Raquel Baeta-Corral, first author of the article, and are the product of a research led by Lydia Giménez-Llort, Director of the Medical Psychology Unit, Department of Psychiatry and Legal Medicine and researcher at the UAB Institute of Neuroscience, together with Dr Björn Johansson, Researcher at the Department of Molecular Medicine and Surgery, Karolinska Institutet and the Department of Geriatrics, Karolinska University Hospital, Sweden, under the framework of the Health Research Fund project of the Institute of Health Carlos III.

Long-term caffeine worsens symptoms associated with Alzheimer’s disease

A group of genes and genetic switches involved in age-related brain deterioration have been identified by scientists at the Babraham Institute, Cambridge and Sapienza University, Rome. The research, published online today (5th March) in Aging Cell, found that changes to one of these genes, called Dbx2, could prematurely age brain stem cells, causing them to grow more slowly. The study was led jointly by Giuseppe Lupo and Emanuele Cacci in Italy and Peter Rugg-Gunn in the UK.

Cells in the brain are constantly dying and being replaced with new ones produced by brain stem cells. As we age, it becomes harder for these stem cells to produce new brain cells and so the brain slowly deteriorates. By comparing the genetic activity in brain cells from old and young mice, the scientists identified over 250 genes that changed their level of activity with age. Older cells turn some genes, including Dbx2, on and they turn other genes off.

By increasing the activity of Dbx2 in young brain stem cells, the team were able to make them behave more like older cells. Changes to the activity of this one gene slowed the growth of brain stem cells. These prematurely aged stem cells are not the same as old stem cells but have many key similarities. This means that many of the genes identified in this study are likely to have important roles in brain ageing.

The research also identified changes in several epigenetic marks – a type of genetic switch – in the older stem cells that might contribute to their deterioration with age. Epigenetic marks are chemical tags attached to the genome that affect the activity of certain genes. The placement of these marks in the genome change as we age and this alters how the cells behave. The researchers think that some of these changes that happen in the brain may alter causing brain stem cells to grow more slowly.

First author on the paper, Dr Giuseppe Lupo, Assistant Professor at Sapienza University said: “The genes and gene regulators that we identified are corrupted in neural stem cells from older mice. By studying the Dbx2 gene we have shown that these changes may contribute to ageing in the brain by slowing the growth of brain stem cells and by switching on the activity of other age-associated genes.”

Co-lead scientist Dr Peter Rugg-Gunn at the Babraham Institute said: “Ageing ultimately affects all of us and the societal and healthcare burden of neurodegenerative diseases is enormous. By understanding how ageing affects the brain, at least in mice, we hope to identify ways to spot neural stem cell decline. Eventually, we may find ways to slow or even reverse brain deterioration – potentially by resetting the epigenetic switches – helping more of us to stay mentally agile for longer into old age.”

Co-lead scientist Dr Emanuele Cacci at Sapienza University said: “We hope this research will lead to benefits for human health. We have succeeded in accelerating parts of the ageing process in neural stem cells. By studying these genes more closely, we now plan to try turning back the clock for older cells. If we can do this in mice, then the same thing could also be possible for humans.”

This article has been republished from materials provided by the Babraham Institute. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference: Lupo, G., Nisi, P. S., Esteve, P., Paul, Y.-L., Novo, C. L., Sidders, B., … Rugg-Gunn, P. J. (n.d.). Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age-associated neurogenic decline. Aging Cell, n/a-n/a. https://doi.org/10.1111/acel.12745

https://www.technologynetworks.com/genomics/news/these-genes-are-involved-in-age-linked-brain-deterioration-298221?utm_campaign=Newsletter_TN_BreakingScienceNews&utm_source=hs_email&utm_medium=email&utm_content=61138279&_hsenc=p2ANqtz-_FeiFbqi-SP5EqlFOOosvK1dViRCt4fG_ztTzGnpct1WLd4sY0BUbdkcuE7-2clIdZwQsKU1fdtv-8HDaJoh76WD9KwA&_hsmi=61138279