Category Archives: Dementia & Carers

Circadian circuit may affect “Sundowning”

News Release
April 9, 2018 | Boston – Beth Israel Deaconess Medical Center

New Discovery May Calm ‘Sundowning’

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BOSTON – Patients with Alzheimer’s disease and other forms of dementia commonly experience the sundown syndrome – a sudden worsening of confusion, agitation and aggression at the end of the day. Its daily pattern suggested that “sundowning,” as the phenomenon is also known, may be governed by the body’s internal biological clock. Synchronized by light and darkness, the circadian clock exerts control over wake/sleep cycles, body temperature, digestion, hormonal cycles and other physiological and behavior patterns. But whether the circadian clock regulated aggressive behavior was unknown.

Now, for the first time, a team of neuroscientists at Beth Israel Deaconess Medical Center (BIDMC) has demonstrated circadian control of aggression in male mice and identified the specific neurons and circuitry regulating the daily pattern. The insight opens the door to potential opportunities for managing the evening-time agitation common in patients with degenerative neurological disorders. The study was published today in Nature Neuroscience.

“Sundowning is often the reason that patients have to be institutionalized, and if clinicians can control this circuit to minimize aggressiveness at the end of the day, patients may be able to live at home longer,” said senior author Clifford B. Saper, MD, Chair of the Department of Neurology at BIDMC. “We examined the biological clock’s brain circuitry and found a connection to a population of neurons known to cause violent attacks when stimulated in male mice. We wanted to know if this represented a propensity for violence at certain times of day.”

Saper and colleagues observed aggressive interactions between male mice – resident mice defending territory against intruders introduced to residents’ cages at different times throughout the day. Counting the intensity and frequency of residents’ attacks on intruders revealed for the first time that aggression in male mice exhibits a daily rhythm.

“The mice were more likely to be aggressive in the early evening around lights out, and least aggressive in the early morning, around lights on,” Saper said. “It looks like aggressiveness builds up in mice during the lights on period, and reaches a peak around the end of the light period.”

Next, the scientists used genetics-based tools to manipulate neurons known to regulate the central circadian clock. When Saper and colleagues inhibited these neurons by disabling their ability to produce a specific neurotransmitter, the mice lost the daily waxing and waning of their aggressive tendencies. These genetically manipulated mice were more aggressive overall, demonstrating a significant increase in total time attacking intruders.

Using optogenetics – a technique that uses light to activate or deactivate targeted brain cells – to map brain circuitry revealed two parallel pathways between the biological clock and a population of neurons in a sub-region of the hypothalamus (called the VMHvl) known to cause violent attacks when stimulated in male mice.

Taken together, the experiments showed that this circadian circuit kept aggressiveness in check in the early morning; stimulating it prevented attack, while inhibiting it promoted attack. Because stimulating the neurons in question cools off aggression, Saper suggests that controlling this circuit could potentially make animals – and perhaps people – less aggressive.

“Our results in mice mimic the patterns of increased aggression seen in patients during sundowning,” Saper said. “This new research suggests this pathway may be compromised in neurodegenerative diseases. Examining changes to this pathway in patients could provide insight into future interventions that could greatly improve the quality of life for patients and caregivers alike.”

In addition to Saper, investigators included co-first authors William D. Todd and Henning Fenselau, Joshua L. Wang, Natalia L. Machado, Anne Venner, Rebecca Broadhurst, Satvinder Kauer, Bradford B. Lowell, and Patrick M. Fuller, of BIDMC and Harvard Medical School; Rong Zhang, of Boston Children’s Hospital and Harvard Medical School; Timothy Lynagh of the University of Copenhagen; and David P. Olsen, of the University of Michigan, Ann Arbor.

This work was supported by the G. Harold and Leila Y. Mathers Foundation and the US National Institutes of Health (NIH) (grants NS072337, NS085477, AG09975, HL095491 NS073613, NS092652, NS103161, DK111401, DK075632, DK096010, DK089044, DK046200, DK057521, NS084582-01A1 and HL00701-15. Additional support came from the Alzheimer’s Association (AARF16-443613), CNPq (National Health Council for Scientific and Technological Development), and CAPES (Coordination for the Improvement of Higher Education Personnel).

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Never stop doing little things for others. Sometimes these little things occupy the biggest part of their hearts.

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Neglect common in English care homes

News Release
March 21, 2018 | London – Neglect common in English care homes

The largest-ever survey of care home staff in England, led by UCL researchers, has found that neglectful behaviours are widespread.

Elder care

For the study, published today in PLOS ONE, care home staff were asked anonymously about positive and negative behaviours they had done or had witnessed colleagues doing.

Dr Claudia Cooper (UCL Psychiatry), the study’s lead author, said: “We found low rates of verbal and physical abuse; the abusive behaviours reported were largely matters of neglect.

“These behaviours were most common in care homes that also had high rates of staff burnout, which suggests it’s a consequence of staff who are under pressure and unable to provide the level of care they would like to offer.”

From 92 care homes across England, 1,544 care home staff responded to the survey. The staff were asked whether they had, in the past three months, witnessed a range of positive and negative behaviours. Their responses were linked to data from each care home describing a measure of burnout in care home staff.

Some negative behaviours were categorised as ‘abusive’, using a standard definition,* and based on the behaviour reported, rather than the intention of the care home staff. The most common abusive behaviours were: making a resident wait for care (26% of staff reported that happening); avoiding a resident with challenging behaviour (25%); giving residents insufficient time for food (19%); and taking insufficient care when moving residents (11%). Verbal abuse was reported by 5% of respondents, and physical abuse by 1.1%.

At least some abuse was identified in 91 of the 92 care homes.

Positive behaviours were reported to be much more common than abusive behaviours, however some positive but time-consuming behaviours were notably infrequent.  For instance, more than one in three care home staff were rarely aware of a resident being taken outside of the home for their enjoyment, and 15% said activities were almost never planned around a resident’s interests.

“Most care homes, and their staff, strive to provide person-centred care, meaning that care is designed around a person’s needs, which requires getting to know the resident and their desires and values. But due to resources and organisational realities, care can often become more task-focused, despite intentions and aspirations to deliver person-centred care,” said co-author Dr Penny Rapaport (UCL Psychiatry).

“Carers can’t just be told that care should be person-centred – they need to be given the support and training that will enable them to deliver it,” she said.

The study is part of the UCL MARQUE cohort study, which is also looking into cost-effective interventions to improve the quality of care for people with dementia, and will be using this anonymous reporting as a measure of how well training interventions are working.

More than two thirds of care homes residents have dementia. Agitated behaviours such as pacing, shouting or lashing out are more common in dementia, and can make provision of person-centred care very challenging for care staff to deliver, often with minimal training and limited resources.

“With the right training, care home staff may be able to deliver more effective care that doesn’t need to be more expensive or time-consuming. If they understand and know how to respond to behaviour, they may be able to do more without greater resources,” said the study’s senior author, Professor Gill Livingston (UCL Psychiatry).

Dr Doug Brown, Chief Policy and Research Officer at Alzheimer’s Society, commented: “70% of people living in care homes have dementia, and it’s clear from these findings that they’re bearing the brunt of a chronically underfunded social care system.

“It’s upsetting but unsurprising that abusive behaviours were more common in homes with higher staff burnout. We’ve heard through our helpline of people with dementia not being fed, or not getting the drugs they need, because a carer isn’t properly trained, or a care home is too short-staffed.

“By 2021, a million people in the UK will have dementia. The government must act now, with meaningful investment and reform, or we risk the system collapsing completely and people with dementia continuing to suffer needlessly.”

The study was conducted by researchers at UCL and the Camden and Islington NHS Foundation Trust, and funded by the Economic and Social Research Council and the National Institute for Health Research.

Links

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Media contact

Chris Lane

Tel: +44 (0)20 7679 9222

Email: chris.lane [at] ucl.ac.uk

Tips to tackle family tension around alzheimer’s

family tips

A useful infographic for families.

Source: https://www.alz.org/documents_custom/ABAMInfographicTipsToTackleFamilyTension.pdf

How Alzheimer’s disease spreads throughout the brain

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Harmful tau protein spreads through networks.
Author provided

Thomas E Cope, University of Cambridge

Alzheimer’s disease is a devastating brain illness that affects an estimated 47m people worldwide. It is the most common cause of dementia in the Western world. Despite this, there are currently no treatments that are effective in curing Alzheimer’s disease or preventing its relentless progression.

Alzheimer’s disease is caused by the build-up of two abnormal proteins, beta-amyloid and tau. Tau is particularly important because it causes neurons and their connections to die, preventing brain regions from communicating with each other normally. In the majority of cases, tau pathology first appears in the memory centres of the brain, known as the entorhinal cortex and hippocampal formation. This has been shown to occur many years before patients have any symptoms of disease.

Over time, tau begins to appear in increasing quantities throughout the brain. This causes the characteristic progression of symptoms in Alzheimer’s diseases, where initial memory loss is followed by more widespread changes in thinking and behaviour that lead to a loss of independence. How this occurs has been controversial.

Transneuronal spread

In our study, published in Brain, we provide the first evidence from humans that tau spreads between connected neurons. This is an important step, because stopping this spread at an early stage might prevent or freeze the symptoms of Alzheimer’s disease.

This idea, called “transneuronal spread”, has been proposed before and is supported by studies in mice. If abnormal tau is injected into a healthy mouse brain, it quickly spreads and causes the mice to manifest dementia symptoms. However, it had not previously been shown that this same process occurs in humans. The evidence from mouse studies was controversial, as the amount of tau injected was relatively high, and disease progression occurred much more rapidly than it does in humans.

Artist’s impression of tau spreading between connected neurons.
Author provided

In our study, we combined two advanced brain imaging techniques. The first, positron emission tomography (PET), allows us to scan the brain for the presence of specific molecules. With this, we were able to directly observe the abnormal tau in living patients, to see exactly how much of it was present in each part of the brain.

The second, functional magnetic resonance imaging (fMRI), measures blood flow in the brain in real time. This allowed us to observe the activity produced by brain regions communicating with each other. For the first time, by scanning the same people with both methods, we were able to directly relate the connections of the brain to the distribution of abnormal tau in living humans with Alzheimer’s disease.

We used a mathematical technique called “graph analysis” to analyse brain connectivity. This technique involved splitting the brain up into 598 regions of equal size. We then treated the connectivity between regions like a social network, assessing factors such as the number of contacts a brain region had, how many “friendship” groups it took part in, and how many of a brain region’s contacts were also contacts of each other.

In a flu epidemic, people with a large number of social contacts are most likely to become infected and then to pass the infection on to others. Similarly, the transneuronal spread hypothesis predicts that strongly connected brain regions will accrue most tau. This is what we observed. This relationship was present within each brain network individually, as well as across the whole brain.

We were also able to exclude potential alternative explanations for the appearance of tau throughout the brain. It had previously been suggested that tau might appear at brain regions that were vulnerable because of high metabolic demand or a lack of support from their neighbours. While it is possible that these factors are important in neuronal death, our observations were not consistent with them being the primary drivers of the initial accumulation of abnormal tau.

In addition, by looking at patients with a range of disease severity, from mild cognitive impairment through to established Alzheimer’s disease, we were able to disentangle the causes of tau accumulation from its consequences. We showed that increasing amounts of tau in Alzheimer’s disease caused the brain to become less connected overall, and the connections that remained became increasingly random.

Long-range connections

Finally, we contrasted the findings in Alzheimer’s disease to a rarer condition called progressive supranuclear palsy (PSP), which affects approximately three in every 100,000 people. This condition is also caused by tau, but it remains confined to the base of the brain. We demonstrated that in PSP the evidence did not support transneuronal spread. This might be because of the different structure of abnormal tau pathology in the two diseases. In Alzheimer’s disease, tau is present in “paired helical filaments”, while in PSP it is in “straight filaments”.

Damaged communications.
Shutterstock

We showed that as PSP progresses, direct long-range connections are preferentially damaged, meaning that information had to take a more indirect route across the brain. This might explain why, when asked a question, patients with PSP usually respond slowly but correctly.

The ConversationOverall, evidence of transneuronal spread in humans with Alzheimer’s disease provides proof of concept for exciting new treatment strategies to lock up tau pathology before it can cause significant damage.

Thomas E Cope, Academic Clinical Fellow, University of Cambridge

This article was originally published on The Conversation. Read the original article.

The onset of Alzheimer’s disease: the importance of family history

News Release
February 26, 2018 | QUEBEC – The onset of Alzheimer’s disease: the importance of family history

You’re about to turn 60, and you’re fretting. Your mother has had Alzheimer’s disease since the age of 65. At what age will the disease strike you? A Canadian study published in JAMA Neurology shows that the closer a person gets to the age at which their parent exhibited the first signs of Alzheimer’s, the more likely they are to have amyloid plaques, the cause of the cognitive decline associated with the disease, in their brain.

In this study involving a cohort of 101 individuals, researcher Sylvia Villeneuve (Douglas Mental Health University Institute; CIUSSS de l’Ouest-de-l’Île-de-Montréal) shows that the difference between a person’s age and the age of their parent at the onset of the disease is a more important risk factor than their actual age.

A 60-year-old whose mother developed Alzheimer’s at age 63 would be more likely to have amyloid plaques in their brain than a 70-year-old whose mother developed the disease at age 85,” explains Villeneuve, an assistant professor at McGill University and a core faculty member at The Neuro’s McConnell Brain Imaging Centre.

Her team of scientists also found that the genetic impact of Alzheimer’s disease is much greater than previously thought.

“Upon examining changes in the amyloid biomarker in the cerebrospinal fluid samples from our subjects, we noticed that this link between parental age and amyloid deposits is stronger in women than in men. The link is also stronger in carriers of the ApoE4 gene, the so-called ‘Alzheimer’s gene’,” says Villeneuve.

Towards earlier detection of the disease

The researcher and her team successfully duplicated their results in two independent groups, one, consisting of 128 individuals from a University of Washington-St. Louis cohort, the other consisting of 135 individuals from a University of Wisconsin-Madison cohort. They also reproduced their results using an imaging technique that enables one to see amyloid plaques directly in the brains of living persons.

Their study is paving the way for the development of inexpensive methods for the early identification of people at risk for Alzheimer’s disease. According to the Alzheimer Society of Canada, 564,000 Canadians currently have Alzheimer’s disease or another form of dementia. The figure will be 937,000 within 15 years. Presently, there is no truly effective treatment for this disease.

This research was funded by grants from a Canadian research chair, the Canadian Institutes of Health Research, the Canadian Foundation for Innovation, the Canadian Brain Research Fund, the Alzheimer Society of Canada, and the Fonds de recherche du Québec — Santé.

The article entitled “Proximity to parental symptom onset and amyloid burden in sporadic Alzheimer’s disease” was published in JAMA Neurology on February 26, 2018. DOI:10.1001/jamaneurol.2017.5135

Source: http://www.douglas.qc.ca/?locale=en

Just the two of us: Holding hands can ease pain, sync brainwaves

News Release
Februarypexels-photo-325884.jpeg 28, 2018 | COLORADO – Just the two of us: Holding hands can ease pain, sync brainwaves

Reach for the hand of a loved one in pain and not only will your breathing and heart rate synchronize with theirs, your brain wave patterns will couple up too, according to a new study.

The study, by researchers with CU Boulder and University of Haifa and published in the journal Proceedings of the National Academy of Sciences (PNAS) this week, also found that the more empathy a comforting partner feels for a partner in pain, the more their brainwaves fall into sync. And the more those brain waves sync, the more the pain goes away.

Key takeaways
  • Holding the hand of a loved one in pain can synchronize breathing, heart rate and brain wave patterns.
  • The more empathy a comforting partner feels for a partner in pain, the more their brainwaves fall into sync.
  • Increased brain synchronization is associated with less pain.

“We have developed a lot of ways to communicate in the modern world and we have fewer physical interactions,” said lead author Pavel Goldstein, a postdoctoral pain researcher in the Cognitive and Affective Neuroscience Lab at CU Boulder. “This paper illustrates the power and importance of human touch.”

The study is the latest in a growing body of research exploring a phenomenon known as “interpersonal synchronization,” in which people physiologically mirror the people they are with. It is the first to look at brain wave synchronization in the context of pain, and offers new insight into the role brain-to-brain coupling may play in touch-induced analgesia, or healing touch.

Goldstein came up with the experiment after, during the delivery of his daughter, he discovered that when he held his wife’s hand, it eased her pain.

“I wanted to test it out in the lab: Can one really decrease pain with touch, and if so, how?”

He and his colleagues at University of Haifa recruited 22 heterosexual couples, age 23 to 32 who had been together for at least one year and put them through several two-minute scenarios as electroencephalography (EEG) caps measured their brainwave activity. The scenarios included sitting together not touching; sitting together holding hands; and sitting in separate rooms. Then they repeated the scenarios as the woman was subjected to mild heat pain on her arm.

Merely being in each other’s presence, with or without touch, was associated with some brain wave synchronicity in the alpha mu band, a wavelength associated with focused attention. If they held hands while she was in pain, the coupling increased the most.

Researchers also found that when she was in pain and he couldn’t touch her, the coupling of their brain waves diminished. This matched the findings from a previously published paper from the same experiment which found that heart rate and respiratory synchronization disappeared when the male study participant couldn’t hold her hand to ease her pain.

“It appears that pain totally interrupts this interpersonal synchronization between couples and touch brings it back,” says Goldstein.

Subsequent tests of the male partner’s level of empathy revealed that the more empathetic he was to her pain the more their brain activity synced. The more synchronized their brains, the more her pain subsided.

How exactly could coupling of brain activity with an empathetic partner kill pain? More studies are needed to find out, stressed Goldstein. But he and his co-authors offer a few possible explanations. Empathetic touch can make a person feel understood, which in turn – according to previous studies – could activate pain-killing reward mechanisms in the brain.

“Interpersonal touch may blur the borders between self and other,” the researchers wrote.

The study did not explore whether the same effect would occur with same-sex couples, or what happens in other kinds of relationships. The takeaway for now, Pavel said: Don’t underestimate the power of a hand-hold.

“You may express empathy for a partner’s pain, but without touch it may not be fully communicated,” he said.

Irit Weissman-Fogel, of University of Haifa, and Guillaume Dumas and Simone Shamay-Tsoory, of Florida Atlantic University, contributed to this study. It was supported with a grant from the Binational Science Foundation.

Source: https://www.colorado.edu/today/2018/02/28/just-two-us-holding-hands-can-ease-pain-sync-brainwaves?utm_source=colorado.edu&utm_medium=Hold%20hands%20to%20ease%20a%20lover%27s%20pain%2C%20and%20your%20brains%20couple%20up%2C%20too&utm_campaign=Homepage&utm_

Written by Lisa Ann Marshall.