Wednesday, December 13, 2017

Detecting anxiety in individuals with Parkinson disease: A systematic review

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Wednesday, 13 December 2017

Detecting anxiety in individuals with Parkinson disease: A systematic review

This is a new systematic review of studies assessing the diagnostic accuracy of anxiety scales in people with PD. It is important because anxiety is a common feature of Parkinson's both before and after the diagnosis. The authors found that overall 30% of people with Parkinson's meet the criteria for anxiety, but I have to say that in my experience I would put it closer to 50%. Maybe this reflects a bias in the patients I see??

The properties of the scales available for assessing anxiety are important. At the beginning of PREDICT-PD, we went through a pain-staking process of selection and in the end arrived at the Hospital Anxiety Depression Scale (HADS). In fact, at that time we knew that it was not the very best Anxiety scale or the very best Depression scale in terms of diagnostic accuracy, but it did combine assessment of both problems in one validated questionnaire, it was feasible to self-administer and it was relatively short. Nearly seven years on I am still happy with that decision but we may now test other scales within the PREDICT-PD programme too. Depression and anxiety are two features that are likely to pre-date a diagnosis of PD by a long time and it is critically important to be using the best tools to identify them both. They also have a dramatic impact on quality of life and are treatable, which are two good reasons to be trying to pick them up in people that don't have a diagnosis because there are likely to be significant health benefits...

Alastair Noyce

Neurology. 2017 Dec 6. pii: 10.1212/WNL.0000000000004771. doi: 10.1212/WNL.0000000000004771. [Epub ahead of print]
Mele B, Holroyd-Leduc J, Smith EE, Pringsheim T, Ismail Z, Goodarzi Z.

OBJECTIVE: To examine diagnostic accuracy of anxiety detection tools compared with a gold standard in outpatient settings among adults with Parkinson disease (PD).

METHODS: A systematic review was conducted. MEDLINE, EMABASE, PsycINFO, and Cochrane Database of Systematic Reviews were searched to April 7, 2017. Prevalence of anxiety and diagnostic accuracy measures including sensitivity, specificity, and likelihood ratios were gathered. Pooled prevalence of anxiety was calculated using Mantel-Haenszel-weighted DerSimonian and Laird models.

RESULTS: A total of 6,300 citations were reviewed with 6 full-text articles included for synthesis. Tools included within this study were the Beck Anxiety Inventory, Geriatric Anxiety Inventory (GAI), Hamilton Anxiety Rating Scale, Hospital Anxiety and Depression Scale-Anxiety, Parkinson's Anxiety Scale (PAS), and Mini-Social Phobia Inventory. Anxiety diagnoses made included generalized anxiety disorder, social phobia, and any anxiety type. Pooled prevalence of anxiety was 30.1% (95% confidence interval 26.1%-34.0%). The GAI had the best-reported sensitivity of 0.86 and specificity of 0.88. The observer-rated PAS had a sensitivity of 0.71 and the highest specificity of 0.91.

CONCLUSIONS: While there are 6 tools validated for anxiety screening in PD populations, most tools are only validated in single studies. The GAI is brief and easy to use, with a good balance of sensitivity and specificity. The PAS was specifically developed for PD, is brief, and has self-/observer-rated scales, but with lower sensitivity. Health care practitioners involved in PD care need to be aware of available validated tools and choose one that fits their practice.

Tuesday, December 12, 2017

Drug lowers deadly Huntington’s disease protein

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Drug lowers deadly Huntington’s disease protein

11 December 2017
The first drug targeting the cause of Huntington’s disease was safe and well-tolerated in its first human trial led by UCL scientists. It successfully lowered the level of the harmful huntingtin protein in the nervous system.
After over a decade in pre-clinical development, this first human trial of huntingtin-lowering drug began in late 2015, led by Professor Sarah Tabrizi (UCL Institute of Neurology) and sponsored by Ionis Pharmaceuticals.
The trial involved enrolling 46 patients with early Huntington’s disease at nine study centres in the UK, Germany and Canada.
Each patient received four doses of either IONIS-HTTRx or placebo, given by injection into the spinal fluid to enable it to reach the brain. As the phase 1/2a trial progressed, the dose of IONIS-HTTRx was increased several times according to the ascending-dose trial design. 
Patient safety was monitored throughout the study by an independent safety committee.
Today’s announcement at completion of the trial confirms that IONIS-HTTRx was well-tolerated by the trial participants and its safety profile supports further testing in patients.
Professor Tabrizi, Director of the UCL Huntington’s Disease Centre and IONIS-HTTRx Global Chief Investigator, said: “The results of this trial are of ground-breaking importance for Huntington’s disease patients and families. For the first time a drug has lowered the level of the toxic disease-causing protein in the nervous system, and the drug was safe and well-tolerated. The key now is to move quickly to a larger trial to test whether the drug slows disease progression.”
A major unknown was whether the trial would show that IONIS-HTTRx could lower the level of mutant huntingtin protein in the nervous system. Using an ultra-sensitive assay, concentrations of the protein were measured in each patient’s spinal fluid before and after treatment.
As hoped, IONIS-HTTRx­ produced significant, dose-dependent lowering of the level of mutant huntingtin – the first time the protein known to cause Huntington’s has been lowered in the nervous system of patients.
As a result of these successful outcomes, Ionis’ partner, Roche, has exercised its option to license IONIS-HTTRx and assumes responsibility for further development, regulatory activities and commercialization activities.   Meanwhile, Ionis announced in June that all patients in the completed trial would be offered a place in an open-label extension to receive IONIS-HTTRx.
The results of the trial and plans for the ongoing IONIS-HTTRx programme will be presented in detail at forthcoming scientific meetings and prepared for peer-reviewed publication.
The research is supported by The National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research CentreThe centre is a partnership between UCL and University College London Hospitals NHS Foundation Trust funded by the NIHR to translate scientific breakthroughs into better patient treatments.


Media contact

Margaret-Anne Orgill

Tel: +44 (0)20 3108 8515
Email: m.orgill [at]

Friday, December 8, 2017

Out of the mouths of babes and sucklings: gut to PD

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Out of the mouths of babes and sucklings

There is an ongoing debate about where Parkinson’s starts. The most accepted hypothesis of Braak and colleagues suggests that it starts outside the brian, either in the olfactory (smelling) nerve, or potentially in the gut. Some evidence suggested that people who had had surgery to cut the nerve to their stomach to treat stomach ulcers were at lower risk of Parkinson’s, which added weight to the theory that Parkinson’s might ‘ascend’ through the nerves of the gut to the brain. This fits nicely with the theory that changes in the microbiome (the overall ecosystem of bacteria and other microorganisms) in the gut plays a part in Parkinson’s. However, this finding has been disputed by other studies.

A report published this month, continues the story elsewhere in the digestive tract. Using the highly reliable public health records of the Danish health and civil registration scheme, they tried to find a relationship between having a tonsillectomy and future risk of Parkinson’s. They examined ther records of over a million people, including 195,000 who’d had tonsillectomy, primarily in childhood. They found 100 people who developed Parkinson’s from the tonsillectomy group at a rate of 0.31 (true figure in the region of 0.22-0.34) cases of Parkinson’s per 100,000 person-years, and 568 cases of Parkinson’s in the comparison group at 0.27 (true figure in the region of 0.29-0.34) cases of Parkinson’s per 100,000 person-years. There was no significant difference between the two groups. Therefore, there is no evidence of any effect of tonsillectomy on the risk of developing Parkinson’s.

This is an important negative finding, and the editor of Movement Disorders should be congratulated on publishing it. It is notoriously difficult to publish ‘negative’ studies, as they rarely make headlines in the broadsheets (when was the last time you read that X had no effect on Y, compared to the last story you read claiming that your favourite food put you at risk of …) Although they found no evidence of an effect, that still isn’t quite the same of finding evidence of no effect; and so the debate rages on.


Tonsillectomy and Risk of Parkinson’s Disease: A Danish Nationwide Population-Based Study
Svensson E1,2Henderson VW1,3,4Szépligeti S1Stokholm MG5Klug TE6Sørensen HT1,3Borghammer P5.

Background: We hypothesized that tonsillectomy modifies the risk of PD.
Objectives: To test the hypothesis in a nationwide population-based cohort study.
Methods: We used Danish medical registries to construct a cohort of all patients in Denmark with an operation code of tonsillectomy 1980-2010 (n = 195,169) and a matched age and sex general population comparison cohort (n = 975,845). Patients were followed until PD diagnosis, death, censoring, or end of follow-up 30 November 2013. Using Cox regression, we computed hazard ratios for PD and corresponding 95% confidence intervals, adjusting for age and sex by study design, and potential confounders.
Results: We identified 100 and 568 patients diagnosed with PD among the tonsillectomy and general population comparison cohort, respectively, finding similar risks of PD (adjusted hazard ratio = 0.95 [95% confidence interval: 0.76-1.19]; for > 20 years' follow-up (adjusted hazard ratio = 0.96 [95% confidence interval: 0.64-1.41]).
Conclusion: Tonsillectomy is not associated with risk of PD, especially early-onset PD. © 2017 International Parkinson and Movement Disorder Society

Tuesday, November 28, 2017

Neuroscience says it's good to daydream

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Neuroscience says it's good to daydream

If your thoughts drift to daydreams of a vacation, neuroscientists say go for it.
If your thoughts drift to daydreams of a vacation, neuroscientists say go for it. (Shutterstock)
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Poets and philosophers have long talked about the quiet, contemplative times of reflection in our lives. Now neuroscientists are finding our brains are really on fire during these restful periods when the brain daydreams.
People had assumed that since we're not doing anything during daydreams that the brain would be on idle.
In fact, a network of activity takes place during daydreams.
The neuroscientists say, daydreams reflect the brain's default mode network — the attentional system when you're not in control of your thoughts and they drift loosely from one to another.  It's when much of our creativity and problem solving occurs.
Dr. Daniel Levitin, an emeritus professor of neuroscience and music at McGill University in Montreal, saw it when he scanned the brain of Grammy winner Sting.
To study brain activity, Levitin uses EEG and a functional magnetic resonance imaging (fMRI) scanner, a machine that noninvasively measures brain activity by detecting changes in blood flow.
Sting and Daniel Levitin
Daniel Levitin shows Sting his cerebellum. ( Owen Egan/McGill University)
When Sting composed in the scanner, Levitin was surprised to find the musician's visual cortex at the back of his head was active. Normally, scientists only see activity there when a subject is watching a movie or dreaming of a scene.
"I asked him about it and he said that when he composes music, he thinks of music as architecture as having different levels of structure and buttresses," Levitin tells CBC Radio Quirks & Quarks host Bob McDonald. "He thinks of it in a very visual, spatial way." 
Levitin says we're experiencing daydreams when the brain drifts as we read, as our eyes seem to get ahead of us and we don't know what we just took in, or when a driver misses an exit on the highway as the conscious part of the brain fails to pay attention.
Dr. Kalina Christoff
Unbridled freedom of thought and spontaneity could be hugely important for creativity but it's only half the story, says Dr. Kalina Christoff. (University of British Columbia)
To neuroscientists, the daydream or default brain network isn't a physical place in the brain. It's a network of brain circuits connected together.
Like Levitin, Dr. Kalina Christoff is drawn to the study of how the default brain network fuels creativity. Christoff is a professor of psychology and Peter Wall scholar at the University of British Columbia in Vancouver.
Christoff first became interested in daydreams during her childhood growing up in Bulgaria. She spent the summers physically wandering through orchards and fields, where she found that letting her mind wander was extremely enjoyable.
As an adult, she realized this resting state of the brain baffled psychologists because they couldn't explain it.
Christoff says most creative people, regardless of the type of art, flip flop between spontaneously brain storming and appraising the results.
"Unbridled freedom of thought and spontaneity could be hugely important for creativity but it's only half of what's necessary," Christoff says. "The other half is to be incredibly critically and in a very constrained way evaluate the products."
But when people show extremes in that range between freedom and constraints in their thoughts, mental illnesses can occur, Christoff says. 
Daydreaming brain
A daydreaming brain: the yellow areas depict the default mode network from three different perspectives; the coloured fibres show the connections amongst each other and with the remainder of the brain. (Max Planck Institute for Human Development )
For instance, she says extreme freedom of thought correlates with the disordered thoughts of psychosis. In depression and obsession, thoughts are extremely constrained.
She says healthy, creative people reach those extremes, but they don't get stuck there.
In contrast in rumination, our thoughts become fixated on a particular worry, such as an argument with a friend.
Christoff collaborates with Dr. Zach Irving of the University of Virginia.
'People with ADHD tend to have more creative achievements than their age-matched peers.'- Dr. Zach Irving
Irving is an assistant professor of philosophy with a personal interest in attention deficit hyperactivity disorder. He was diagnosed as being on the spectrum for ADHD as an adult and was drawn to study how his mind works differently from others.
In ADHD, daydreams or mind wandering is exaggerated, Irving says. It can have costs in terms of not being able to concentrate in class, but it also has benefits.
"People with ADHD tend to have more creative achievements than their age-matched peers," Irving says.
He acknowledges there's been a bit of a pushback from some in the ADHD community with more severe forms who don't want the debilitating aspects of the illness to be characterized as a positive. It's important to consider how ADHD affects someone's life, Irving says.
Irving sees the limitations of research that fails to distinguish between concepts like mind wandering and rumination. It's why he and Christoff published what he calls a dynamic framework for mind wandering in a recent issue of Nature Reviews Neuroscience.
At her lab, Christoff continues to study how people talk their way through puzzles that have no obvious answer. The puzzles offer a non-technological way for her to explore how creativity relates to spontaneous thought.
Other neuroscientists are exploring how daydreams contribute to intelligence.
Last month, Christine Godwin, a PhD candidate at the Georgia Institute of Technology, published a study based on brain pattern measurements of more than 100 people who laid in a MRI machine.
Those who reported more frequent daydreams scored higher on intellectual and creative ability and had more efficient brain systems as measured in the MRI, Godwin found.

Thursday, November 23, 2017

The Circadian Clock in Your Nose

The Circadian Clock in Your Nose

A new study found that your sense of smell may fluctuate in tune with your circadian clock.CreditBrian Harkin for The New York Times
When people tell you, “wake up and smell the roses,” they might be giving you bad advice. Your sense of smell may fluctuate in sensitivity over the course of 24 hours, in tune with our circadian clocks, with your nose best able to do its job during the hours before you go to sleep, according to a study published last month.
The work, reported in the journal Chemical Senses, is part of a larger push to explore whether adolescents’ senses of taste and smell influence obesity. Rachel Herz, a sensory researcher at Brown University, and her colleagues designed this study to see if there might be times of day when the sense of smell was more powerful — perhaps making food smell particularly inviting.
For the experiment, 37 adolescents ranging in age from 12 to 15 came into a lab for a very long sleepover party. For nine days, they followed a strict schedule to allow researchers to focus on the circadian clock, which helps control wake and sleep, but also influences other processes in the body, including metabolism.
While more research is needed to test whether the results fully apply to adults, Dr. Herz says that as you grow up, the makeup of the smell receptors inside your nose doesn’t seem to change, although there is evidence your body clock may.
The team kept track of where the teenagers were in their circadian cycle by measuring their saliva’s levels of melatonin, a hormone that rises and falls regularly over the course of the day. Every few hours, the children took a scent test, sniffing different concentrations of a chemical that smells like roses. The researchers recorded the lowest concentration they could detect at each time point.
When the results were tallied up, the researchers saw a range of responses. “Nobody has the same nose,” Dr. Herz said. Some adolescents had only very mild changes in sensitivity, while sensitivity altered dramatically in others.
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Averaged together, however, the results showed that overall the circadian clock does affect smell, and that the times when the children’s noses were most sensitive tended to correspond to the evening, with an average peak of 9 p.m.
“The results make sense — the circadian clock affects virtually every organ system in the body,” writes Dr. Leslie Vosshall, a researcher at Rockefeller University who studies smell and was not involved in the study, in an email.
Smell was at its lowest ebb, intriguingly, from about 2 a.m. to 10 a.m.
It is already known that when we are asleep, a strong smell won’t disturb us the way a loud noise or a bright light will. Perhaps the biological machinery behind smell shuts itself down for the night, at least in some people. But Dr. Herz speculates that having stronger olfactory abilities as dusk fell might have helped our ancestors survive.
“It really underscores the importance of auditory fire alarms,” she said.
Still, the experiment was designed to test the effect of the circadian clock, and that is not the only factor involved in smell sensitivity. Researchers have already found that another big player is how long someone has been awake and what variety of smells they have been exposed to. It’s likely that all of these have a role in determining when, in real life outside the lab, our sense of smell works best.
A version of this article appears in print on , on Page D2 of the New York edition with the headline: Your Nose Knows: Circadian Clocks And Sense of Smell Go Hand in HandOrder Reprints | Today’s PaperSubscribe