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Canada’s National Newspaper of the CNS Sciences n August 2018 n The Chronicle is committed to maintaining leadership in environmentally sustainable policies, and to encouraging the adoption of “greenaware” practices in healthcare. We invite your comments via e-mail, at: email@example.com
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Editorial: Connecting weight and cognitive function..................3 Off-label meds mainstay in treating pediatric headaches ..........10 High cortisol reactivity increases risk of anxiety diagnosis ......15
Biomarking holds untapped potential for dementia care Alzheimer’s disease
Link driven by genes, environment
n Increased depression, worse physical health
by Bianca Quijano,
Assistant Editor, The Chronicle
riteria for diagnosing
g o dc
the different types of dementia vary in the extent to which they involve biomarking. this may explain why biomarkers are not utilized as extensively in treating this patient population compared to those with other conditions such as cancer, according to dr. sandra Black, the executive director of the toronto dementia research alliance. “advances in our field are allowing us to understand genetic risk markers and biochemical abnormalities at birth
n o i ni t
and throughout life,” said dr. Black during a presentation at the 9th Canadian Conference on dementia in toronto. “But the problem is that it has not been easy to have everybody agree on standardization. for example, in scandinavia, alzheimer biomarkers and cerebrospinal fluid are regularly obtained. in north america and some parts of europe, that is not the case.” dr. Black, who is also the director of the Hurvitz Brain sciences research Program at sunnybrook research institute in toronto, said that current —please turn to page 6
Annual CPA conference coming in September the Canada Psychiatric association’s 68th annual conference Conference
please turn to page 12
Wellness poorly assessed in patients
is scheduled to have an added focus on current key issues facing patients and their families, such as mental health initiatives for military personnel. this year’s congress, sept. 27 to sept. 29, will be held in toronto. —see page 11
n Gap caused by gender bias in clinic visits, few treatment options by John Evans, Associate Editor, The Chronicle
ellness issues in Patients witH MultiPle sClerosis (Ms), including dietrelated factors as well as quality-of-life matters related to bladder, bowel, and sexual symptoms, are not being addressed as well as clinicians might hope, according to data from two surveys of participants in the north american research Committee on Ms (narCoMs) registry. the survey data were published in two papers: treatment satisfaction and bothersome bladder, bowel, sexual symptoms in multiple sclerosis (Multiple Sclerosis and —please turn to page 9 Related Disorders feb. 2018; 20:16–
This issue’s Chronicle Vitae profiles Dr. Tom Feasby, who has been named to the Order of Canada. He is the founder of the country’s leading stroke research and treatment program. See page 18
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“We think sometimes we’re only drawn to the good, but we’re actually drawn to the authentic. We like people who are real more than those who hide their true selves under layers of artificial niceties.”
—Dr. Elizabeth Kübler-Ross, American-Swiss psychiatrist (1926–2004)
Guest editorial: Connecting weight and cognitive function He days wHen (HealtHy) skePtiCisM CHallenged
the link between obesity and cognitive function are over. large, longitudinal studies have now provided strong evidence supporting a link between markers of obesity, such as body-mass index (BMi), waist-to-hip ratio, and cognitive performance. for instance, the 1946 British Birth Cohort study found that young/mid-life adults with higher BMi and waist circumference displayed worse memory and psychomotor speed 20 years later (Masi, et al, 2018). these findings are consistent with another large, 20-year follow-up study showing that obesity during midlife was an Dr. Frey independent predictor of both mild cognitive impairment and dementia later in life (knopman, et al, 2018). the fact that obesity in adulthood is a risk factor for late life cognitive dysfunction is particularly worrisome to countries like Canada, where almost 30% of adults are clinically obese (statistics Canada. table 13–10–0794–01 Measured adult body mass index (BMi) (world Health organization classification), by age group and sex, Canada and provinces, Canadian Community Health survey—nutrition).
SURVEYING CURRENT HYPOTHESES However, an important question that remains unanswered is: “what are the mechanisms behind obesity and cognitive dysfunction?” Many hypotheses have been proposed to explain such a link, including genetic predisposition, inflammation, sleep disturbances (e.g., sleep apnea), hormonal factors (e.g., insulin signalling), changes in brain structure and function (e.g., loss of grey matter in certain brain regions), metabolic dysfunction, depression, and alterations in the “gut-brain axis.” this exciting area of current research has revealed biological pathways that will hopefully help the development of effective
ABOUT THE AUTHOR Dr. Frey is an associate professor at the Department of Psychiatry and Behavioural Neurosciences at McMaster University in Hamilton and Academic Head of the Mood Disorders Program, and Director of the Women’s Health Concerns Clinic at St. Joseph’s Healthcare in Hamilton. His research interests include: the cerebral mechanisms involved in the neurobiology of bipolar and major depressive disorder, with an emphasis in female-related psychiatric conditions; development of brain imaging and peripheral biomarkers to understand the course and treatment of mood disorders; and the role of circadian rhythms in postpartum depression and anxiety.
new therapeutics. for instance, a recent study including 1,255 participants found that higher BMi and alterations in the white matter microstructure in the corpus callosum, left arcuate thalamic radiation, and left superior longitudinal fasciculus were associated with poorer performance in executive function and processing speed (Zhang, et al, 2018). another recent study found that obese individuals were less efficient during an implicit learning performance task and such “cognitive inefficiency” was associated with less connectivity between the striatum and premotor and its associative areas (Mathar, et al, 2017). together, these studies highlight changes in brain structure and function in obese individuals that lead to poorer cognitive performance. OBESITY AND PSYCHIATRIC DISORDERS Perhaps the impact of obesity on cognitive performance may be particularly relevant for individuals with psychiatric disorders, given that certain disorders such as depression, bipolar disorder and schizophrenia, are associated with a much greater risk for obesity and metabolic dysfunction. for instance, a longitudinal study of six years of follow-up showed that obesity (as measured by BMi) was an independent predictor of poorer cognitive performance in individuals with bipolar disorder (Mora, et al, 2017). interestingly, in a study of 120 individuals with first-episode psychosis, being obese or overweight was associated with “advanced brain age” (kolenic, et al, 2018). However, it is still uncertain whether these brain and cognitive abnormalities associated with obesity in individuals with psychiatric disorders can be attenuated or corrected with treatment or changes in life style. in conclusion, obesity, a major public health concern, is strongly associated with cognitive impairment and risk for late life dementia. new research suggests several possible mechanisms linking obesity with cognitive dysfunction. Peripheral changes in pro-inflammatory cytokines, stress hormones, alterations in the gut-brain axis may lead to abnormalities in brain structure and function. these abnormalities presumably underlie the alterations in executive function, learning, and memory observed in obese subjects. while we hope that these exciting data will guide the development of new targeted treatments, one should not forget the importance of healthy diet and exercise. a recent update on behavioural interventions to improve cognition and school achievement in obese children and adolescents found that both dietary and physical interventions significantly improved cognitive function and school achievement (Martin, et al, 2018). notably, obese children with better physical fitness displayed better academic performance and greater gray matter volumes in frontal, temporal, and limbic brain regions (esteban-Cornejo, et al, 2017). so let’s not forget the basics! think weight!
The Chronicle of Neurology & Psychiatry is published six times annually by the proprietor, Chronicle Information Resources Ltd., with offices at 555 Burnhamthorpe Rd., Ste. 306, Toronto, Ont. M9C 2Y3 Canada. Telephone: 416.916.2476; Fax. 416.352.6199. E-mail: firstname.lastname@example.org. Contents © Chronicle Information Resources Ltd., 2018, except where noted. All rights reserved worldwide. The Publisher prohibits reproduction in any form, including print, broadcast, and electronic, without written permissions. Printed in Canada. Mail subscriptions: $72 per year in Canada, $125 per year in all other countries. Single copies: $12 per issue (plus 13% HST) Canada Post Canadian Publications Mail Sales Product Agreement Number 40016917 The Publisher certifies that advertising placed in this publication meets Revenue Canada requirements for tax deductibility. Volume 21, Number 2 published August 2018 ISSN 1209-0565
n In a study aiming to investigate the
relation of diet quality with structural brain tissue volume and focal vascular lesions, it was concluded that better diet quality related to larger brain volume, grey matter, white matter, and hippocampal volume. These findings suggest nutrition may affect brain structure via neurodegeneration. This study was published online ahead of print in Neurology (May 16, 2018). —Find more info at goo.gl/Qwr2xg
n Researchers identified variants in the
same pathway for childhood-onset schizophrenia (COS) in the ATP1A3 gene and in certain cases an association with rare variants in the FXYD gene family. ATP1A3 has previously been linked with COS in only one case report. This association is novel and highlights the interest of exploring these genes in COS. This is according to a study published online ahead of print in Molecular Psychiatry (June 12, 2018). —Discover more info at goo.gl/eksBe6
n In a case-control pharmacoepidemi-
logical study researchers sought to quantify the association of extrapyramidal symptoms (EPSs) with different antidepressants. In the study published online ahead of print in J Clin Psychpharmacol (June 12, 2018), researchers found a harmful association between the incidence of Parkinson’s disease or associated EPSs and use of certain antidepressants. —Learn more at goo.gl/74eptL n Researchers developed an automated technique to identify and analyze laminar structure within the high resolution 3D histological BigBrain. By bridging high resolution 2D cytoarchitecture and in vivo 3D neuroimaging, researchers were able to map cross-cortical patterns of laminar architecture in histological section. These findings offer possibilities for more precise characterizations of the nature of structural changes associated with neuropsychiatric conditions and for lining such characterizations to functional disturbances (Cerebral Cortex July 2018; 28(7):2551-2562). —Learn more at goo.gl/Hfe16u August 2018 n 3
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This image was created by an artist in her late 80s who attends an art therapy group for people living with early-to-mid-stage dementia and their care partners. This was her first time using modelling clay, and as a group we explored the medium by viewing and discussing the artwork of contemporary artists who work with this material, and then creating our own relief images. “It’s every little bird on every little tree,” said the artist who created this image. With this piece, she expressed the pure joy she finds in watching birds, and connected with her memory of feeding birds in her own backyard. Her daughter-inlaw, who accompanies her in the group, noted the pride that her mother-in-law felt after creating this piece. Exploring a new art medium helped her to not only connect with her emotions and her past experiences, but also to reconnect with her identity as an artist. —Brianna Kestle, Registered Psychotherapist (Qualifying), Art Therapist —More information at www.briannakestle.com
n Dementia: Cognitive enhancers considered safe and effective for alzheimer’s disease (p. 7) n MS: Health Canada approves new medication for primary progressive multiple sclerosis (p. 8) n Headache: off-label medication use mainstay in treating youth (p. 10) n Anxiety: Children with behavioural inhibition at greater risk of social anxiety diagnosis (p. 14) n TBI: identifying risk factors for Cte (p. 16) n TBI: forecasting outcomes for concussion in children (p. 17) Photo courtesy of CAMIMH
s Quick-start guide to The Chronicle, August 2018:
J. J. Warsh,
Sarah A. Morrow,
Roger S. McIntyre,
Editor, Innovation in the Mind Sciences Editorial Director
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4 n August 2018
Images from the world of neurological and psychiatric medicine: we invite you to submit your photographs for tHe CHroniCle of neurology + PsyCHiatry. send original high-resolution (2 megapixels and higher) JPgs to: email@example.com.
The seven Champions of Mental Health award winners were recognized by the Canadian Alliance on Mental Illness and Mental Health (CAMIMH) and Bell Canada’s Let's Talk initiative at a gala in Ottawa on May 8, 2018. The winners were Kristin Legault-Donkers (the Sharon Johnston Champion of Mental Health Award for Youth; fifth from right), Traci Melchor (Media; right photo), Linda Corkum (Workplace Mental Health; fourth from right), the British Columbia Aboriginal Network on Disability Society (Community Organization; represented by Ray McGuire, far left), Josee Parent (Community Individual; second from left), Majid Jowhari (Parliamentarian), and Dr. Stanley Kutcher (Innovation by a Researcher or Clinician, far right). Kristin Legault-Donkers received the award for her four written and published books, the Children's Mental Health Series, which is currently being used in over 100 elementary schools. Broadcaster Traci Melchor was recognized with the Champions award in the Media category for using her platform at Bell Media to reduce the stigma of mental disorders.
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“The stronger person is not the one making
the most noise but the one who can quietly direct the conversation toward defining and solving problems.” —Dr. Aaron T. Beck, American psychiatrist
Brain “fingerprint” Excess self-criticism in young children can predict efficacy raises risk of OCD diagnosis later in life of medications n Inclination also linked to anorexia, social anxiety, other disorders
with tendencies toward perfectionism and excessive self-control are approximately twice as likely to develop obsessivecompulsive disorder (OCD) by their teenage years, researchers report in a new study from the Washington University School of Medicine in St. Louis. Published in JAMA Psychiatry (July 18, 2018, online ahead of print), the research was inspired in part by earlier observations that the anterior cingulate cortex (ACC), which is implicated in the pathogenesis of OCD, is also associated with performance monitoring. The investigators aimed to see if an observed indicator of heightened performance monitoring during preschool age was associated with later onset OCD and altered dorsal ACC (dACC) volume through adolescence.
TRAITS OF EXCESS SELF-CRITICISM “Having a lot of self-control and striving for perfection often are considered by parents and society as good because they can eliminate mistakes, but excessive self-control and perfectionism raise a red flag,” said the study's lead author, Kirsten E. Gilbert, PhD, in a press release from the university. “In adolescents and adults, these characteristics are associated with OCD and other disorders, such as anorexia and social anxiety. We’ve now been able to link this to OCD risk in children.” Dr. Gilbert is an instructor in child psychiatry at Washington University. The longitudinal, observational cohort study was conducted at a single academic medical centre as part of the Preschool Depression Study. A sample of 292 children oversampled for depression between Sept. 22, 2003 and May 12, 2005 completed a performance-based observational task, in which they received persistent negative evaluation. Blind raters then behaviourally coded the children’s performance monitoring. Participants completed annual
n Researchers report Canadians
with PTSD who use medical cannabis are 60 to 65% less likely to have major depressive episodes or thoughts of suicide compared to those who do not use medical marijuana. The observational study using cross-country data from Statistics Canada was reported by The Globe and Mail (May 31, 2018). —Find more information at goo.gl/BpbcYP
n New research finds, despite
diagnostic assessments over the following 12 years. From the original sample, 133 children completed the final behavioural follow-up, and 152 children contributed one to three magnetic resonance imaging (MRI) scans. A final follow-up was completed on Aug. 14, 2017. PERFORMANCE MONITORING The researchers found that among the 292 children who had completed the baseline evaluation (51.4% male, mean [SD] age, 4.5 [0.8] years), after controlling for both demographic and clinical indicators, the children with observed heightened performance monitoring were twice as likely to develop OCD within the following 12 years (odds ratio, 2.00; 95% CI, 1.06-3.78; p=0.03). As well, multilevel modelling of dACC volume across three scan waves in the 152 children who provided MRI scans revealed that heightened performance monitoring was also associated with a smaller right dACC volume (intercept estimate, -0.14; SE, 0.07; t=-2.17; p=0.03). “One of my interests, ideally, is to create therapies geared toward prevention,” Dr. Gilbert said. “We also want to look at the role of parenting, because if one of these kids has a parent who is always saying, ‘That is not good enough!', you can see how this problem could spiral.” —More information at goo.gl/mS7Xc9
observing improved psychiatric and behavioural states, commonly-prescribed antipsychotic pills derail metabolism in teens and raise their diabetes risk. Children on certain ADHD medications gained weight and fat tissue, and became more insulin sensitive in just 12 weeks. These findings were reported by the Daily Mail (June 13, 2018). —Read this article at goo.gl/AHg1zc
Copyright-free photo from Max Pixel via goo.gl/fLZ9oi
INTERVENTION Fingerprint (pTIF) is a newly developed form of personalized medicine that researchers are using to predict the effectiveness of targeting specific biological factors to control the progression of disease. Researchers studied specific biological factors including, brain amyloid/tau deposition, inflammation, and neuronal dysregulation (NeuroImage June 14, 2018). Investigators used computational brain modelling and artificial intelligence techniques to analyze neurological data from 331 patients with Alzheimer's disease and healthy controls. Data was collected using positron emission tomography (PET) and magnetic resonance imaging (MRI) to categorize patients into TIF subtypes. These subtypes were classified according to the potentially most beneficial factor-specific interventions which were verified for relevance using the patient's genetic profile. It was discovered that patients within the same pTIF subtype had similar gene expression, indicating similar physiological mechanisms. Since the targeted medications were tailored to different disease progression based on genetic expression and brain properties, different treatments for pTIF subtypes in Alzheimer's patients was predicted to be more effective compared to the same treatment for all subtypes. “In keeping with the tenets of personalized medicine, the introduced framework could lead to more effective medical care, decreased undesired secondary effects, and substantial reduction of pharmaceutical/clinical costs associated with clinical trials, thereby accelerating the creation-evaluation cycle of new therapeutic agents,” said first author Dr. Yasser Iturria-Medina, assistant professor in the Department of Neurology and Neurosurgery at McGill University in Montreal. Knowing this link between pTIF subtypes and therapeutic response can lead to medications that are designed based on patients’ genetic profiles. —Read more information at goo.gl/ncfH97 HERAPEUTIC
In the news . . .
n The World Health Organization
recently announced compulsive video game playing now classifies as a mental health condition in an effort to help governments, families, and health care workers be more vigilant and prepared to identify the risks. The Toronto Star (June 18, 2018) reports psychiatrists are treating gaming addictions with psychological therapies and in some cases using medication to overcome the addiction. —Read more at goo.gl/gBqLyr
n After examining the caudate and
putamen brain regions, researchers report that a stronger response is observed when participants are presented both fats and carbohydrates together compared to either one independently. Results indicate that these foods trigger stronger cravings reports Forbes (June 14, 2018). —More information at goo.gl/XAPcGM August 2018 n 5
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Identifying risk for dementia diagnosis using biomarkers
—Continued from page 1
ning patterns. results were published in the journal diagnostic measures for dementia, such as the national NeuroImage (sept. 2017; 28(17):98–108). the researchers compared brain scans from two groups institute of neurological and Communicative disorders and of elderly patients—those with high blood pressure and stroke and the alzheimer’s disease and related disorders those without high blood pressure. the trial suggested that association (ninCds-adrda) alzheimer’s Criteria, are high blood pressure caused cortical thinning in vulnerable being updated to implement biomarker requirements. watershed brain areas. BENEFITS OF BIOMARKING furthermore, dr. Black pointed out that vascular vulnerBiomarkers indicate the presence, severity, or progression of ability in these brain areas coincide with hubs involved in neta disease. they are typically identified through measures of work degeneration in ad. cellular and biochemical analyses of body fluids and tissues “severe periventricular white matter disease is related to or brain and body imaging techniques. venous collagenosis involving the deep periventricular veins according to dr. Black, biomarkers are needed to help [in the cerebrum],” said dr. Black, clinicians identify individual pathoreferring to a study published in logical profiles and target personalthe journal Stroke (Mar. 2009; ized treatment options. [Biomarkers are] the way to 40(3):48–52 and more comprehen“we are making the invisible vissively in the Journal of move towards precision ible,” said dr. Black. “we are starting Neuropathology and Experimental to know what is not good to have, medicine, which will help us Neurology (apr. 2017; 76(4):299– but we may not know exactly what to 312). do about it.” take into account the extent to which other since identifying biomarkers pathologies, such as diabetes and individual variability in allows clinicians to see pathological high blood pressure, increase vaschanges for the full spectrum of discular vulnerabilities and impact genetic, endophenotypic, ease, including pre-symptomatic dementia diagnoses can be and environmental factors, explored using neuroimaging biostages, they may also help clinicians utilize prophylactic measures that can in the treatment of various markers according to dr. Black. delay or prevent disease onset. “Hypertension and physical “[Biomarkers are] the way to medical disorders activity are emerging as extremely move towards precision medicine, —Dr. Sandra Black, executive director important for brain health,” she which will help us take into account of the Toronto Dementia Research Alliance said. “older subjects with demenindividual variability in genetic, and director of the Hurvitz Brain Sciences tia often have mixed pathologies. endophenotypic, and environmental Research Program at Sunnybrook there seems to be a combined factors, in the treatment of various Research Institute in Toronto. attack on the aging brain.” medical disorders,” said dr. Black. genetic factors may also impact imaging biomarkers in dementia the diagnosis of these vascular disinclude magnetic resonance imaging eases, which can be further informed by genetic profiles. (Mri) and Positron emission technology. dr. Black noted that in the future, biomarking may also utilize wearable tech- USE IN CLINICAL PRACTICE nologies that measure mobility, cardiac, and circadian although primarily used for research investigations, to the present time, neurodegeneration and visible vasculopathy rhythms. markers can be used in clinical practice. SUCCESS IN ACADEMIC RESEARCH amyloid positron imaging tomography (Pet) has been Biomarker research has been effective in identifying possible used successfully in clinical drug trials to show target engagegenetic markers for dementia. ment, though not yet clinical efficacy. dr. Black noted a study of fetuses which showed that dr. Black cited a study that tested the efficacy of bapbrain development differed in apolipoprotein e4 (apoe4) ineuzumab, published in The Lancet Neurology (Mar. 2012; carriers compared to non-apoe4 carriers. the investigation 11(3):241–249). the drug did show reduction in amyloid suggests that apoe4 is not only an important risk factor for burden in some treated cases but without clinical benefit. alzheimer’s disease (ad) in late life, but the drug was also associated with amyloid-related imaging one that is at work from birth. results abnormalities (aria) in 17% of participants in whom Mri were published in the journal JAMA signal abnormalities suggestive of vasogenic oedema and Neurology (Jan. 2014; 71(1):11–22). cortical microbleeds (aria-H) were noted during treatthrough Mri scans and other imag- ment with bapineuzumab. ing techniques, clinicians can look for and she cited another study that tested the anti-amyloid antiidentify brain signatures and network body, aducanumab, published in Nature (sept. 2016; degradation patterns that may indicate or 537(7618):50–56). in patients with prodromal or mild ad, Dr. Black one year of monthly intravenous infusions of aducanumab show propensity for disease. for example, neuroimaging biomarkers were used to reduced amyloid-β (aβ) plaques with positive effects on show a link between high blood pressure and cortical thin- the Clinical dementia rating—please turn to page 10
6 n August 2018
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Cognitive enhancers considered safe and effective for Alzheimer’s disease
n Donepezil shows highest chance of efficacy, although the therapeutic option is associated with more negative side-effects Copyright-free photo from pixabay.com via goo.gl/SxZaEa
by John Evans,
Associate Editor, The Chronicle
LITERATURE REVIEW OF THE USE OF COGNITIVE
enhancers in Alzheimer’s disease (AD) has found that in general the medications have small, but clinically significant, effects on cognition, and they appear to be safe. These findings were published in the Journal of the American Geriatrics Society (2018; 66(1):170-178). The review included 142 studies—110 randomized controlled trials, 21 non-randomized controlled trials, and 11 cohort studies—that had investigated any combination of donepezil, rivastigmine, galantamine, or memantine used in the treatment of patients with AD. Part of the impetus behind the study came from interest from both geriatricians and health policymakers, including the Ontario Public Drug Policy Research Network, said lead author Andrea C. Tricco, PhD, in an interview with THE CHRONICLE OF NEUROLOGY + PSYCHIATRY.
DONEPEZIL MOST LIKELY TO BE EFFECTIVE “We found that donepezil was the most likely to be effective, especially in improving cognition,” said Dr. Tricco. “However, we saw that there were some sideeffects with donepezil—side-effects such as nausea, vomiting, and diarrhea.” “Donepezil has been around for a long time and I think that [these findings] were consistent with clinical insight that donepezil would likely be the superior medication. However, there are some side effects that one would have to consider if they were potentially thinking about taking these medications,” she said. A Bayesian network metaanalysis of the included papers revealed that donepezil, donepezil plus memantine, galantamine, and transdermal rivastigmine improved cognition more than placebo. Donepezil plus memantine Dr. Tricco improved behaviour more than placebo. Donepezil, donepezil plus memantine, oral rivastigmine, and galantamine all improved global status more than placebo, and galantamine also decreased patients’ odds of mortality.
INTERPRETING THE FINDINGS These findings are consistent with the findings of other analyses, said Dr. Serge Gauthier, director of the Alzheimer’s Disease Research Unit at the McGill Centre for Studies in Aging in Montreal, in an interview with THE CHRONICLE OF NEUROLOGY + PSYCHIATRY. “There is a detectable clinical benefit, and this is reflective of the outcomes of the clinical trials [in the existing literature],” he said. However, Dr. Gauthier notes that there has been a change in the placebo groups over the 10 years of data collection this meta-analysis encompasses. “There is
the term ‘cohort effect’ or ‘generation effect.’ Patients are in better health, even with Alzheimer’s disease, at the end of 10 years when the data was collected.” he said. “The care for people with dementia has improved a lot. We prevent strokes, we control diabetes correctly, and we treat depression very well.” This makes it harder to show AD stabilization with medication, he said.
TREATMENT SAFETY None of the agents examined in the review raised patients’ risks of severe adverse events, falls, or bradycardia. However, it is important to note that very few of the included studies reported on these important adverse events. Some increased risk was seen for headache (oral rivastigmine), diarrhea (oral rivastigmine, donepezil), nausea (oral rivastigmine, donepezil, galantamine), and vomiting (oral rivastigmine, donepezil, galantamine). These safety findings were surprising, but welcome, said Dr. Gauthier. “They found the medicaDr. Gauthier tions are fairly safe. They did not pick up an effect on heart rate and syncope. So that is reassuring,” he said. “If you compare this analysis with older ones from which people may have got the message that the medications can be harmful—causing people to faint and then break a leg—that did not come out at all in [Dr. Tricco and colleagues’] analysis.” The measure of effect used in this meta-analysis— minimal clinically important difference, defined in the paper as a 3.50- to 3.95-point increase in Mini-Mental State Examination (MMSE) score—is not typical, said
Dr. Gauthier. “In Canada, usually to assess treatment effects we use the Cohen index . . . That is something that clinicians and, I think, the people who pay for medications—health economists—are used to.” “The Cohen index would be a more generalizable type of tool to reflect success,” he said.
FUTURE RESEARCH DIRECTIONS It is importanr that researchers such as Dr. Tricco and her colleagues continue to have an interest in looking at the available data on AD medications and examining efficacy, safety, and effect size, said Dr. Gauthier. He said research such as this meta-analysis will be of use in the evaluation of future medications, to assess the efficacy, safety, and cost-benefit for the next generation of medications. “We will have models to work with, based on the old [medications].” Dr. Tricco and her colleagues have reached out to 103 authors and five sponsors of the randomized controlled trials included in their review that reported selected outcomes of interest for a future study. Their goal is to collect individual patient data for each randomized study, and to perform an analysis on factors such as age, sex, and severity of symptoms. “We are attempting to do an individual patient data Network Meta-Analysis to actually see how we can specifically tailor treatment to specific patient characteristics,” she said. Non-proprietary and brand names of therapies: ketamine (Ketalar, ERFA Canada); midazolam (Midalozam Injections, Pfizer Canada Inc.); donepezil (no branded products); memantine (no branded products); galantamine (no branded products); rivastigmine (no branded products).
August 2018 n 7
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Ocrelizumab: New therapy for primary progressive MS n Medication reduced confirmed disease disability progression and hyperintense lesions
by Kyra White,
Editorial Intern, The Chronicle
MEDICATION ALSO REDUCES T2 LESIONS ocrelizumab is a humanized monoclonal antibody that targets the Cd20 antigen found on certain B cells of the immune system. the medication is administered by intravenous infusion every six months. Patients’ first two doses of 300 mg are given two weeks apart, followed by subsequent doses of a single 600 mg infusion. Previously, Ms was thought to be driven by t cells, however due to improved understanding of the pathology, treating Ms with a B cell depleting therapy, such as ocrelizumab, became a possibility. the therapy’s effectiveness was measured using the expanded disability status scaled (edss) to quantify physical deterioration. researchers found a 24% relative risk reduction in confirmed disability progression (CdP) compared to placebo, as measured by the edss (p=0.03). lastly, it was found that over 120 weeks, there was a 3.4% reduction of total volume of brain hyperintense t2 lesions compared with a 7.4% increase in placebo-treated patients (p<0.001). ocrelizumab’s safety was evaluated in the oratorio study, which was a randomized, double-blind, global multicentre study that assessed 486 patients and noted the most common adverse drug reactions (adr). these adrs included: infusion-related reactions, upper respiratory tract infections, and influenza, compared to placebo. “you always have to
8 n August 2018
Copyright-free photo from Wikimedia Commons via goo.gl/VJSs22
ealtH Canada Has aPProved tHe first MediCation, ocrelizumab, for patients living with primary progressive multiple sclerosis (PPMs). PPMs impacts 10 to 15% of Canadians living with the rare condition, and until now, these patients had no promising treatment options. “this is exciting news for the multiple sclerosis community,” said dr. karen lee, vice-president of research at the Multiple sclerosis society of Canada, in a press release. Dr. Lee it is estimated that 100,000 Canadians are living with multiple sclerosis (Ms), one of the highest prevalence rates in the world. Because of the high number of cases, the disease is commonly referred to as “Canada’s disease.” PPMs is a debilitating form of the condition which can result in difficulty walking among many other symptoms. unlike relapsing-remitting multiple sclerosis (rrMs) which makes up 85% of Ms cases, PPMs is characterized by the steady worsening of neurological function, without periods of remission and relapse. “we tried in the past a number of different drugs, but unfortunately all of them were negative, and finally this drug ocrelizumab . . . has demonstrated a positive effect on PPMs for the first time ever,” said dr. Xavier Montalban, professor of medicine and the department division director, neurology, at the university of toronto and director of the Barlo Multiple sclerosis Centre at st. Michael’s Hospital, in an interview with tHe CHroniCle of neurology & PsyCHiatry.
check the risk-to-benefit ratio and make a decision. the older you are the higher risk you have, of course,” said dr. Montalban. despite the adrs, ocrelizumab is a game-changer for the PPMs community, noted dr. Montalban. “we are now modifying the natural history of the disease. if you compare what happened to cohorts we studied 25 years ago with what happened to the modern cohort of patients, the history is completely different,” he said. dr. Montalban also noted the importance of managing patient expectations. “in Ms there are a number of patients who unfortunately have a very serious condition, and they have quite a high degree of disability. Because of the neurode-
generative process there is nothing [we can] do,” he said. dr. Montalban explained that patients may have different endpoints relative to their particular degree of disability to which the therapy can provide relief. it is important that patients have realistic expectations and be aware that the drug may not be successful in certain instances. ocrelizumab offers eligible PPMs patients the opportunity to delay disease progression and psychological support in the form of hope for the future. ocrelizumab is not a cure, but a step Dr. in the right direction, explained dr. Montalban Montalban. Patients living with PPMs and physicians are hopeful this drug will help control and slow the progression of the disease. “Hopefully, this is the beginning of many more treatment options for people living with Ms,” said dr. lee.
Non-proprietary and brand name of therapy: ocrelizumab (Ocrevus, Hoffmann-La Roche Limited).
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Few treatments available for MS patients with bladder, bowel, sexual problems Copyright-free photo from pixabay.com via goo.gl/J1Ge81
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21), and Diet quality is associated with disability and symptom severity in multiple sclerosis (Neurology Jan. 2, 2018; 90(1):e1-e11). “One of the things we like to do with this registry [NARCOMS] is tackle issues that may be not as well dealt with or discussed as much, to try to see how much they are affecting individuals with MS and to raise awareness about the concerns,” said Dr. Ruth Ann Marrie in an interview with THE CHRONICLE OF NEUROLOGY + PSYCHIATRY. Dr. Marrie, who was the senior author on the diet paper and a contributing author on the other paper, is a professor in the departments of internal medicine (neurology) and community health sciences at the University of Manitoba in Winnipeg, as well as the director of the university’s MS clinic. BLADDER, BOWEL, SEXUAL SYMPTOMS The symptom paper included data from 9,341 respondents, 77.4% women, with a mean (SD) age of 50.3 (10.5) years. Among the respondents, 91% were mildly, moderately, or severely bothered by bladder, bowel, or sexual symptoms. Medical providers are aware of these symptoms, which are associated with spinal cord involvement in MS, but the patient survey showed low patient satisfaction with the treatments for those symptoms, said Dr. Marrie. She said that is likely partly due to the fact that while there are some treatment options for these symptoms, there are not as many options as practitioners might want, and the existing therapies often have undesirable side-effects. The observed low satisfaction rate with available therapies for these symptoms was discouraging to Dr. Marrie. “In some ways that is not a surprise, given we still have some limited options for those treatments. But Dr. Marrie it is important, and unfortunate after all this time, knowing that people have these symptoms, that we have not managed to find more effective therapies for these affected individuals,” she said. As well, not all care providers were asking about these symptoms. Only 62.1% of respondents said their practitioner had asked them about bladder problems, 51.1% said they’d been asked about bowel problems, and 20.6% had been asked about sexual problems. “The other thing that is striking is the gender difference in terms of asking about the degree of bother about symptoms, and whether or not providers are asking about them,” Dr. Marrie said. Male respondents were twice as likely to report that their healthcare provider had asked them about sexual dysfunction. “But women also have sexual dysfunction,” said Dr. Marrie. “So there seems to be potential provider-based gender biases in terms of asking about some of these
symptoms. This means we are probably not dealing with the symptoms in women as well as we could be.” These types of biases are typically unconscious, she said, but practitioners need to become aware of them so that they can avoid them. The interest in the role of diet in MS disability and symptom severity arose from an increase in attention among patients with MS on wellness and the potential for lifestyle changes to improve overall health, Dr. Marrie said. “As healthcare providers we also want to be able to encourage behaviour change. There has not been a great deal of high quality literature about the effect of diet on multiple sclerosis.”
DIET REDUCES DISABILITY There were 7,639 respondents to the diet survey, of whom 6,989 reported physician-diagnosed MS and also provided dietary information. The data showed that those participants who had diet quality scores in the highest quintile had lower levels of disability as measured using Patient-Determined Disease Steps (PDDS)—proportional odds ratio [OR] for quintile five vs. quintile one =0.80; 95% confidence interval [CI] 0.69–0.93. That quintile also had lower depression scores—proportional OR for quintile five vs quintile one 0.82; 95% CI 0.70–0.97. Those who reported a composite healthy lifestyle also had lower odds of reporting severe fatigue (0.69; 95% CI 0.59–0.81), depression (0.53; 95% CI 0.43–0.66), pain (0.56; 95% CI 0.48–0.67), or cognitive impairment (0.67; 95% CI 0.55–0.79). The diet findings “are consistent with what we might have predicted based on what we are seeing in other diseases,” said Dr. Marrie. “Healthier diets, particularly when coupled with healthy behaviours, are associated with people feeling better. The findings were particularly interest-
ing for fatigue [and depression] that can be particularly debilitating for people with MS.” While the survey data were corrected based on annual household income as a measure of socio-economic status, it was not equipped to evaluate factors such as access to good quality food or exercise facilities, Dr. Marrie noted. With the evidence that diet quality may play a role in reducing disability and symptom severity in MS, the question of how to ensure patient diet is of high quality arises, she said. Practitioners “need to make sure they are actually asking [patients] what they are doing in terms of their physical activity and their diet,” Dr. Marrie said. “To try and ensure we offer the appropriate education about what we think may be helpful in terms of management of the disease.” This includes having conversations with patients about what barriers to good diet they might be experiencing, and possible management strategies. If a patient is too tired at the end of the day to make a good quality meal, they might use a slow-cooker to pre-prepare batch meals on weekends when they are more able to rest, for example. Diet is an important wellness area to focus on because of the wide scope of its benefits, Dr. Marrie said. “If we can improve MS and also improve all of the other things that go with a healthy diet, then other positive health benefits such as lower risk of cancer and heart disease, then it will have been a worthwhile thing to have spent time on.” It is important to remember that the cross-sectional nature of this survey means it is not possible to say why some patients are doing better, Dr. Marrie said. “But I think it is consistent with our feeling that we need to be looking at this area [diet] more.” August 2018 n 9
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Off-label use of medication is a mainstay of treating headaches in children
n Lack of published scientific studies on efficacy of treatments in pediatric populations means that physicians often turn to alternatives
by Bianca Quijano,
Assistant Editor, The Chronicle
if pediatric patients are still not responsive to triptans or higher dosages, dr. Callen recommends moving on to adolescent-graded medications or even mental health therapies that may be able to discern other issues that are contributing to their headaches. in the emergency room setting, it is protocol to place pediatric patients in a dark quiet room and giving them intravenous fluids. this likely is not harmful and is not evidenced-based, said dr. Callen.
who experience migraines and other types of headaches is not evidence-based. since there is very little scientific literature on the effectiveness of certain medications, physicians and neurologists often go off-label when treating children, dr. david Callen reported during a presentation at the annual Paediatric update PLACEBO EFFECT, ALTERNATIVE INTERVENTIONS Conference in toronto. Holistic interventions can be recommended to patients because the placebo effect is ibuprofen, for example, a mainstay therapy for pediprofound in the pediatric migraine and headache populaatric headaches, has been studied at doses of 10 mg/kg, yet tion. most neurologists including dr. Callen, prescribe it at 20 Patients have seen a 30 to 60% reduction in headache mg/kg (Expert Opin Pharmacother 2002; 3(10):1433–1442). When we look at those red furthermore, the efficacy of acetaminophen, another comwith placebo, making it an effective treatment for flags and other treatment decreasing the frequency of migraine (J Pediatr oct. 2014; mon medicine used for headaches, has only been analyzed once in a 1997 study (Neurology 1997; 48(1):103–107). it was in addition, studies have shown that factors, all those things that 165(4):659–665). found to be 1.3 times more effective than placebo. current medications (i.e., valproic acid, topiramate, acetaminophen is also often combined with other medica- we used to believe, we should amitriptyline) produce results no better than placebo (N tions, but the study did not investigate its efficacy when Engl J Med Jan. 2017; 376(2):115–124). not necessarily believe. used in this context. “i get migraines myself. i have a hard time believing “i was flabbergasted at just how little evidence there is that i am psychologically developing this and that i have A lot of these come from out there for medications that we use all the time, especially a placebo effect when i take medication. But this is what adult cases. evidence specifically in children,” said dr. Callen, program the evidence shows me,” said dr. Callen. director of the Pediatric neurology residency and active interventions such as music therapy, cognitive —Dr. David Callen, program director fellowship training Program at McMaster university in behavioural therapy, and weekly relaxation therapy have of the Pediatric Neurology Residency Hamilton. “But that lack of evidence does not mean that also been proven to cause a substantial decrease in the and Fellowship Training Program at these treatments do not work.” frequency of headaches over time (Pain May 1986; McMaster University in Hamilton. 25(2):195–203). PEARLS FOR PRESCRIBING MEDICATIONS OFF-LABEL “it is just difficult for us to be able to do these cogdespite the lack of evidence supporting the efficacy of medicines, dr. Callen has nitive interventions because of a lack of resources in our system. at times, i wish developed a specific treatment strategy for children with headaches. i could prescribe placebo because it would do no harm and could potentially be these medications should not be taken more than three beneficial. But we do not really have that option at this point,” said dr. Callen. times per week to avoid medication overuse headaches. at the uCH of wHat is PraCtiCed in tHe treatMent of PediatriC Patients
beginning of a headache, he prescribes 20 mg/kg to a maximum of 3,200 mg per day of ibuprofen as an abortive therapy. He recommends that patients take this with acetaminophen 20 mg/kg to a daily maximum of 4,000 mg. “Has this been studied? absolutely not. does it seem to work? yes. nobody has come back to me saying that this is terriDr. Callen ble for them because there is not a lot of side effects. i am probably going to stick with this for a while,” said dr. Callen. the next line of abortive medications for headaches are triptans. However, dr. Callen rarely prescribes them because of associated side effects and bad taste of nasal spray formulations. variations that he prescribes on occasion are zolmitriptan and rizatriptan. “usually if we nip the headache with the high dose of acetaminophen, that is good enough. at the beginning we always talk about, Hit it hard, hit it fast,” he said. trying higher dosages of these medications can also improve efficacy. “if a patient, for example, fails to see results with ibuprofen, they usually have not used a big enough dose or they usually have not used it with acetaminophen,” said dr. Callen.
RED FLAGS FOR CHILDREN similar to the treatment options, there is little evidence showing that established red flags of migraines and headaches are accurate indicators of conditions. additional considerations must also be taken when assessting medical therapies for pediatric patients. for instance, physicians know that further interventions are needed when patients report experiencing the “worst headache of their life.” Patients who say this are most likely adults who have had a lifetime of experience with varying degrees of headaches. Children on the other hand would not be able to properly verbalize the severity of their symptoms. “when we look at those red flags and other treatment factors, all those things that we used to believe, we should not necessarily believe. a lot of these come from adult cases,” said dr. Callen.
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of dementia disorders. dr. Black emphasized that there is tremendous opportunity for molecular imaging, cerebrospinal fluid (Csf) biomarking, as well as proteomic biomarking through cheek swabs, salivary, and blood analyses. with or without biomarkers, dr. Black stressed that treating neurodegenerative diseases, particularly the different types of dementia, will always be a unique challenge compared to other conditions. “the brain has special ways of being heterogenous,” explained dr. Black. “there are only so many ways you can hurt a heart or a lung. there are a lot of ways you can hurt different brain networks with very different resulting clinical manifestations.”
Non-proprietary and brand names of therapies: acetaminophen (Tylenol, Johnson & Johnson); amitriptyline (Elavil, AA Pharma Inc); propranolol (Inderal, Sandoz Canada); zolmitriptan (no branded products); rizatriptan (no branded products); ibuprofen (Advil, Wyeth).
More biomarking techniques in development for Alzheimer’s disease therapy
sum of Boxes (Cdr-sB) and Mini Mental state examination (MMse) scores. “amyloid imaging is now becoming a requirement to credential patients for entry into anti-amyloid antibody clinical [drug] trials,” said dr. Black. she added that there need to be new endpoints for clinical trials in the presymptomatic stage of ad. for example, many of the scales used in current ad trials are not geared specifically for people in the very early stages of the disease. a standing clinical trial infrastructure that allows for rapid testing, consistent high-quality data, and prompt data uploads is also needed.
POTENTIAL FOR PROTEOMIC BIOMARKING, OTHER TECHNIQUES More biomarking techniques are being developed for treating the wide spectrum 10 n August 2018
Non-proprietary and brand names of therapies: bapineuzumab (not licensed in Canada); aducanumab (not licensed in Canada).
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Toronto to host the 68th annual Canadian Psychiatric Association conference
n This year’s educational Congress runs from September 27 to 29 and will feature current key issues facing patients and their families Copyright-free photo from pixabay.com
by Kyra White,
Editorial Intern, The Chronicle
Canadian PsyCHiatriC association (CPa) is hosting its 68th annual conference in toronto, sept. 27 to 29 at the westin Harbour Castle. this year’s conference will include national and international speakers, with topics ranging from the integration of technology into the world of psychiatry to the burden of mental health in military, veterans, and public safety personnel. “we are excited about the range of topics, and being responsive to our mental health providers, but also the current key issues that are facing our patients and their families,” said dr. sanjeev sockalingam in an interview with tHe CHroniCle of neurology + PsyCHiatry. dr. sockalingam is a psychiatrist and associate professor at the university of toronto and the chair of the CPa annual conference program subcommittee. “this a very relevant conference and an opportunity to learn from experts about current practices and how to navigate some of the challenging but relevant topics in mental health and addiction,” said dr. sockalingam. He
CPA AT THE MOVIES “alice Cares” will be the feature film at this year’s CPa conference and will be screened sept. 28 from 4:30 p.m. to 6 p.m. “this is something that continues to be a mainstay of our program . . . this year we have a particularly relevant movie because it focuses on a robot providing support to another individual,” said dr. sockalingam. the film addresses the role of robots and technology in mental health support for individuals and opens a dialogue on how these advances will be incorporated into future clinical practices. the event will be hosted by dr. Harry karlinsky, a clinical professor in the department of Psychiatry at the university of British Columbia in vancouver. CPA ACADEMY UPDATE COURSES a longstanding conference symposium is the CPa expert Psychiatry series, presented this year in partnership with the Canadian academy of Psychiatry and the law, noted dr. sockalingam. leaders in the field drs. Joel watts, Philip klassen, and Brad Booth will present a practical approach to assessing and presenting evidence on different levels of patient capacity. “one of the things we continue to expand on is our specialty areas in psychiatry. the Canadian academy of Psychosomatic Medicine, Child and adolescent Psychiatry, and geriatric Psychiatry are all providing updates on what is new and cutting edge,” said dr. sockalingam.
SPECIAL ACTIVITIES FOR RESIDENTS the CPa will be hosting special activities for residents at this year’s annual conference. on sept. 27 a resident’s competition will take place, giving residents an opportunity to partake in friendly competition and showcase their knowledge, explained dr. sockalingam. following the competition, residents may partake in a “Meet your Members-in-training section executive” and share ideas to promote the interest of Canadian psychiatric trainees and fellows. the day will conclude with a social networking event for residents, fellows, and medical students from across Canada.
HOST CITY AND SOCIAL ACTIVITIES as a torontonian, dr. sockalingam believes the host city, toronto, provides attendees a great opportunity to immerse in the diverse night life, world renowned cuisine, and lively theatre district that the metro has to offer. “there are a lot of entertainment opportuPhoto of 2017 CPA Conference from goo.gl/8TSYdW
ALL-DELEGATE KEYNOTE PLENARY with many new faces and returning favourites, the keynote plenary sessions will be one of many highlights at the conference, noted dr. sockalingam. on sept. 27 the topic of technology and the future of mental health with perspectives on care and compassion will be presented by dr. Brian Hodges and dr. lisa Marsch. the presentation will discuss advances in technology and how psychiatrists can integrate and leverage technology in their everyday practice. dr. Hodges is a professor in the faculty of Medicine at the university of toronto, the richard and elizabeth Currie Chair in Health Professions education research at the wilson Dr. Sockalingam Centre, and executive-vice President of education at the university Health network. dr. Marsch is the director of the Center for technology and Behavioural Health and the andrew g. wallace Professor at the geisel school of Medicine at dartmouth College, Hanover, n.H. dr. don richardson, dr. andrea tuka, and dr. nicholas Carleton will present about mental health in military, veterans, and public safety personnel with approaches to psychiatric assessment and care delivery on sept. 28. the presentation will include an overview, will review treatment of military-related Ptsd, and discuss the importance of treating comorbidity to improve outcomes. dr. richardson is a consultant psychiatrist and Physician Clinical lead at the Parkwood operational stress injury Clinic in london, ontario. dr. tuka is the Clinical leader at the operational trauma stress support Center at the royal Canadian navy Base in esquimalt, B.C. dr. Carleton is a profes-
sor of Clinical Psychology, a doctoral clinical psychologist in saskatchewan, and is currently serving as the scientific director for the Canadian institute for Public safety research and treatment. dr. Phil tibbo will present the topic of cannabis on sept. 29 with a focus on how it relates to mental health disorders. dr. tibbo is a professor in the department of Psychiatry at dalhousie university in Halifax.
nities to supplement the valuable learning that people will experience,” he said. for those who wish to attend, the conference will also be hosting a gala dinner the evening of sept. 28. August 2018 n 11
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Bi-directional relationship exists between brain health and
Associate Editor, The Chronicle
Besity and iMPaired Cognition
interact in a mutually reinforcing way that can also involve mood disorder and systemic inflammation. these links can make treatment more challenging and contribute to poorer outcomes and shorter life expectancies, according to new evidence. “science has taken us in a direction where we have learned there is a bidirectional, two-way street between the brain and obesity,” said dr. roger Mcintyre in an interview with tHe CHroniCle of neurology + PsyCHiatry. dr. Mcintyre is a professor of psychiatry and pharmacology at the university of toronto, and head of the Mood disorders Psychopharmacology unit at the university Health network (uHn), toronto. “once someone has accumulated excess weight and adiposity, we begin to see changes occurring in their brain,” he said. as well, abnormalities in the brain and brain function have been shown to lead to obesity. “what is really interesting is that the brain regions that are affected by obesity, and the brain regions that result in obesity, are similar regions,” dr. Mcintyre said. these include the regions involved in reward and in cognitive control. dr. Mcintyre said that some of the best evidence for this connection is that cognitive improvements have been observed in patients who have undergone bariatric surgery to treat obesity. a literature review was conducted (Psychosomatics May/June 2017; 58(3):217-227) of studies that looked at various neurocognitive domains, including attention and executive function, memory, and language, after bariatric surgery to treat obesity. the review authors noted that each of the 10 included studies documented statistically significant improvements in at least one cognitive domain, though the differences in study design and outcome measures made meta-analysis impossible. limitations the authors listed also included a lack of a standardized comprehensive neurocognitive assessment modality for bariatric surgery patients, the potential that studies with negative results were not published biasing the data, and that only two of the included studies examined the potential impact of adipokines on neurocognitive changes after bariatric surgery--which made it difficult to quantify neurocognitive changes in the domains of interest.
WIDER RECOGNITION OF LINK NEEDED the relationship between excess weight or obesity and neurological health is quite well established scientifically, but is not as well recognized in clinical practice, said
12 n August 2018
dr. rodrigo Mansur, speaking with tHe CHroniCle. “when we talk about depression and obesity, some people are still surprised by the association.” dr. Mansur is a staff psychiatrist at uHn in toronto and an assistant professor, brain and thera-
peutics, in the department of Psychiatry at the university of toronto. His research focus is on the interaction between metabolic and mood disorders. in a review where he was lead author (Neuroscience and Biobehavioural Reviews 2015; 52:89–104), dr. Mansur and his colleagues concluded that there was accumulating evidence in the literature of a consistent association of multiple abnormalities in neuropsychological constructs, as well as corresponding brain abnormalities, with metabolic dysfunction. among the papers included in that review, some specifically looked at a link between cognition and weight or metabolism, including: “Cognitive dysfunction associated with metabolic syndrome” (Obesity Reviews sept. 2007; 8(5):409–418), “longitudinal examination of obesity and cognitive function: results from the Baltimore longitudinal study of aging”
(Neuroepidemiology May 2010; 34(4):222– 229), and “elevated body mass index is associated with executive dysfunction in otherwise healthy adults” (Comprehensive Psychiatry Jan.-feb. 2007; 48(1):57–61). “in neurology i think [the link between metabolic conditions and cognitive issues] is strongest in alzheimer’s disease,” said dr. Mansur. “diabetes, for example, is a well-known risk factor for alzheimer’s, though there is also some evidence for Parkinson’s disease.”
Photo by Jennifer Burk via unsplash.com (https://goo.gl/4eCbJw)
by John Evans,
EXCESS WEIGHT, COGNITION, MOOD DISORDERS the risk of comorbid obesity appears to increase with the severity of mental illness as well, noted dr. valerie taylor. “[obesity] is over-represented in depression, but rates of obesity are higher in bipolar than they are in depression, and they are higher in schizophrenia than they are in bipolar.” dr. taylor is Psychiatrist-in-Chief at women’s College Hospital in toronto, and an associate professor in the department of psychiatry at the university of toronto. “obesity is separately, independently related to problems with cognition,” dr. taylor said. “there have been a number of studies showing that being overweight or obese in mid-life or later life is a risk factor for not just vascular dementia but for alzheimer’s dementia as well.” this link is through mechanisms such as hypertension, stroke, and white matter changes in the brain, and also separately through increased deposit of the plaques and tangles associated with alzheimer’s dementia, she said. “and, of course, mental illness is associated with cognitive changes as you get older,” said dr. taylor. “so when you have both mental illness and obesity, cognitive risk increases even more.”
LESS WEIGHT IMPROVES COGNITION another significant piece of evidence that obesity and cognition are tied together comes from research into outcomes after bariatric surgery, said dr. Mcintyre. “if [a patient] goes for bariatric surgery, which is an effective treatment for morbid obesity, in addition to having significant adipose tissue loss, what one also observes is corrective changes in the brain structure.” from a scientific perspective, showing that obesity results in cognitive impairment is compelling, said dr. Mcintyre. showing that removal of obesity results in a restoration of cognitive performance is even more compelling that this is not merely an association, but a cause. dr. Mcintyre notes as well that children and adults with untreated attention-deficit/hyperactivity disorder (adHd) are more likely to be obese than the
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POTENTIAL MEDIATORS DESCRIBED There are a number of potential mediating factors that might have a role in this inter-relationship between obesity and neurological health. “What we are implicating more and more are changes in inflammation and changes in insulin resistance,” said Dr. McIntyre. “As your adipose tissue becomes larger, the adipose tissue is producing pro-inflammation [molecules], which itself has a negative effect on the brain’s structure and function.” Genetic factors may also play a role, said Dr. Mansur. "Metabolic and mood disorders share some genetic vulnerabilities." While he said that this should not be surprising—both are complex and heterogenous—this suggestion of genetic pleiotropy could indicate that there is a mechanistic connection between the two types of disorders, and may inform researchers about the specific biological pathways involved and reveal new targets to explore for therapy in the future. This shows that both gene and gene-environment interactions play a role. Lifestyle, including physical exercise, dietary patterns, and sleep patterns can also play a role, Dr. Mansur said, as well as medical-related factors. “The main discussed [medical factors] are medications. Some—though not all—medications used in the treatment of mental health problems can and do affect metabolism and weight in general.” Weight gain from medication use is not sufficient to explain the association on its own, he said, as there is data from first episode studies that individuals first diagnosed with mental illness, but not yet medicated, have higher rates of obesity than the general population.
ORBITAL FRONTAL CORTEX DAMAGE, OTHER CORRELATES OF COGNITIVE CHANGE There is ongoing research into the changes that occur in the brain related to obesity. Stephanie Borgland, PhD is an associate professor at the Hotchkiss Brain Institute at the University of Calgary who with her colleagues is investigating in animal models how areas of the brain involved in reward and motivated behaviour change in response to different diets or exposure to addictive Dr. Borgland drugs. In an interview with THE CHRONICLE OF NEUROLOGY + PSYCHIATRY she explained that one area of the brain of interest to their research is the orbital frontal cortex. “In humans, that area of the brain is very important for decision making, especially decision-making in an emotional context,” she said. “People with ablations in that area of the brain have a hard time making decisions.” The orbital frontal cortex has been shown in previous research to be involved in sensory-specific satiety. This is the ‘buffet effect’ or ‘turkey dinner’ effect, where an individual is receiving physiological satiety signals from having eaten enough, but find themselves motivated to eat further when encountering a highvalue food item, such as dessert after a large meal. “Some of our preliminary findings have been that obese rodents are less sensitive to sensory-specific satiety,” she said. “So [the rodents] will continue to consume or engage in actions to get food, even though they have been pre-sated on that type of food.”
S o m e humans who have frontot e m p o r a l dementia, with neurodegeneration in the frontal cortex, may be aware of satiety but have trouble inhibiting themselves from continuing to eat food, Dr. Borgland said. The rodent studies of sensory-specific satiety have shown that the affected animals have changes in the inhibitory control of pyramidal neurons, making them more excitable. “How that specifically controls behaviour, we are still trying to figure out,” she said. “We have shown that if you artificially inhibit that inhibitory control of the pyramidal neurons, then lean mice will also become insensitive to this sensory-specific satietytype devaluation.” As well, obesity leads to a release of the cytokine lep-
“I think there is resistance
in the field to accept mental illnesses as full-body illnesses . . . Even though we have learned over the decades that brain and body are connected—everything that affects the brain affects the body, and vice-versa,”
—Dr. Rodrigo Mansur, assistant professor of Brain and Therapeutics in the Department of Psychiatry at the University of Toronto and staff psychiatrist at the University Health Network in Toronto. .
tin from adipose tissue, which has been shown to influence the hypothalamus, Dr. Borgland said. “The hypothalamus is the area of the brain that can control motivated behaviour, but can also control a variety of homeostatic behaviours such as temperature, food intake, and satiety.” INTER-DISCIPLINARY APPROACH A challenge to addressing this association is there is a bit of a siloing of expertise, said Dr. Taylor. “Sometimes as mental healthcare providers we want to focus on what it is we are trained to treat. If someone comes to us and they are now diabetic, or they are starting to gain weight, we assume that is going to be taken care of, or is the role of, a different specialist. “I think we need to understand that these things actually are important for us too, as mental healthcare
providers, because they have direct impact on the way in which a lot of the mental illnesses play out in terms of their symptom profile and in terms of how people respond to treatment.” Noting that prevention is easier than treatment, Dr. Taylor said that if a patient starts a pharmaceutical therapy for a mood disorder and begins to gain weight, have an abnormal lipid profile, or have their blood glucose increase, she would consider switching to a different medication. If the current medication is working well for the patient’s mental health, however, she would seek to integrate with the patient’s primary care doctor or with other specialists to develop strategies to manage the weight gain and lipid abnormalities. “I think there is resistance in the field to accept mental illnesses as full-body illnesses,” said Dr. Mansur. “Which I think is a key concept that even psychiatry itself resists. There is this classical, historical idea that psychiatric illnesses are different, they are separate. Even though we have learned over the decades that brain and body are connected—everything that affects the brain affects the body, and vice-versa.” PUBLIC HEALTH IMPLICATIONS There are also public health implications to the connections between weight and neurological health. “We have a lot of data, quite consistent as well, that individuals with mood and psychotic disorders die much earlier than the general population,” said Dr. Mansur. “Their life expectancy is between ten and fifteen years lower. There are many reasons for that, but one reason is they face a lot of barriers to access healthcare. They are more likely to have heart attacks, but they are less likely to receive adequate prevention for it.” These patients are less likely to be prescribed anti-blood pressure medication, less likely to be diagnosed with heart attack, and less likely to receive adequate treatment for such an attack, he said. Treatment adherence, too, is impacted, said Dr. Taylor. “Weight gain as a consequence of psychiatric treatment is one of the top reasons why people stop taking their medications. People really feel as if they are being forced to choose between which chronic illness they want to have. That is really an impossible situation to put our patients in.” If mental health practitioners do not take these patients’ weight concerns seriously, the patients will often seek alternative solutions on their own, she said. They may purchase unsafe or unhelpful products from the internet that may be prohibitively expensive, and failure to lose weight on these programs can have additional impact on mood.
August 2018 n 13
Photo by Sandra Cohen-Rose and Colin Rose via flickr.com (goo.gl/1JwGvR)
general population. “In part, one reason that we think that is the case is that the brain’s cognitive control networks are abnormal. And the abnormal cognitive control networks, the networks responsible for regulating normative eating, are in fact aberrant, abnormal. So the person is eating to excess.”
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Children with BI at greater risk of social anxiety diagnosis n Link is specific to social type of anxiety, tendency to dwell on errors also a contributing factor important as well,” she said.
by Bianca Quijano,
Assistant Editor, The Chronicle
WEIGHING TREATMENT OPTIONS the study stresses the importance of taking a developmental eHavioural inHiBition (Bi) in CHildHood can predict the later development of social anxiety in adolescence, approach to understanding social anxiety. Parents and cliniaccording to a study published in J Am Acad Child Adolesc cians should pay closer attention to children with Bi, who are Psychiatry (2017; 56(12):1097–1105). in a subset of 268 partic- at a higher risk of developing social anxiety. “social anxiety is not just something that appears in your ipants, investigators concluded that children with Bi who office one day when you are an adult or already an adolescent,” dwell or become pre-occupied with errors they have made are said dr. Buzzell. at a higher risk of developing social anxiety later in life. that being said, dr. Henderson stressed that not all chil“if they are slowing down [after error detection] is that dren with Bi will develop social anxiety. making them more accurate on the next task? if it is cautious“the connection between ness, slowing down should improve behavioural inhibition and social anxtheir accuracy,” said senior study iety is not one-to-one,” she said. “it is author george a. Buzzell, Phd, Clinically what results really important to remember that postdoctoral fellow at the university many toddlers who are behaviourally of Maryland in College Park, Md. suggest is that children’s inhibited and fearful of social situa“But in our data set we checked that attention is getting stuck tions—many of them turn out just and it was not leading to improved accuracy. so, we took the tentative when they are experiencing fine. and that is with no intervention, that is just through living their interpretation that perhaps they are life as they normally would and learnsocial anxiety. They have a not being more cautious, rather, they ing how to manage their error preocare ruminating on their errors— hard time shifting their cupations through experience.” something that we see in children Parents with children who have attention away from with social anxiety.” Bi do not, at the outset, need to enroll STUDY METHOD DESCRIBED potential mistakes that their children in therapy or a psychithe researchers assessed Bi in chilatric assessment. treatment action is they have made. dren who were two and three years of only necessary when Bi symptoms —Dr. Heather Henderson, professor in the age. Children were videotaped and escalate and persist over time, to the Department of Psychology at the monitored through an electroenpoint that they interfere with the University of Waterloo in Waterloo, Ont. cephalogram while performing an child’s ability to function in their daily eriksen flanker task under two conenvironment (i.e., school) or their abilditions—first while knowing that they were being observed by ity to maintain decent quality friendships with at least a few their peers and once while believing that they were not being other children. observed. this novel technique targeted “we can think about this at a more preventative level. changes in brain activity (error monitoring) Parents can start by talking to their children about attention and behaviour (slowing down after error and talking about mistakes as an enormous and transformative detection) specific to social situations. part of everyone’s life. this may prevent kids from ever going at 12 years old, social anxiety sympdown the pathway of social anxiety,” said dr. Henderson. toms and social anxiety diagnoses of the participants were recorded through self- SOCIAL ANXIETY AFTER ADOLESCENCE reports from children and parents, as well drs. Buzzell and Henderson’s investigation is part of an ongoDr. Buzzell as clinician interviews. results illustrated ing longitudinal research program lead by dr. nathan fox, senthat social error-related negativity changes ior study author and professor, institute for Child study and explained relations between Bi and social anxiety symptoms department of Human development at the university of (n=107) and diagnosis (n=92). Maryland. the researchers are continuing to follow this cohort of children as they IMPLICATIONS OF RESULTS grow older, to see how their error monitor“Clinically what results suggest is that children’s attention is geting brain and behavioural activities evolve ting stuck when they are experiencing social anxiety. they have over time. the participants are performing a hard time shifting their attention away from potential mistakes similar tasks, but now they are being that they have made,” said study co-author Heather Henderson, observed as they interact with other Phd, professor at the university of waterloo in waterloo, ont. Dr. teenagers who they have never met before. dr. Henderson highlighted that although it is hypotheHenderson “we are bringing them in to get a comsized that error responses precede manifestations of anxiety, it could also be that anxious children are particularly prone to prehensive assessment of not only how they report their feelings, but also so that we can observe what they are actually like pay attention to their errors. “it could be the other way around . . . for clinicians, think- when they are with children that they are unfamiliar with,” said ing through what is the chicken and what is the egg in this is dr. Henderson.
14 n August 2018
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Parental anxiety and high cortisol reactivity increases pediatric anxiety risk
n Administering early psychiatric intervention among guardians with social anxiety may prevent onset of diagnosis in their children
Assistant Editor, The Chronicle
HILDREN WITH SOCIALLY ANXIOUS
parents and increased cortisol reactivity are more likely to develop persistent and clinically significant social anxiety, according to a study published in J Abnorm Child Psychol (Aug. 2018; 46(6):1309–1319). The findings suggest a joint influence of familial vulnerability and biological stress reactivity on social anxiety. Researchers say this illustrates the importance of considering interactions between biological and contextual factors in tackling the development, maintenance, and therapeutic options for children with social anxiety. Specifically, considering not only child-level biobehavioural factors but also the environmental influences surrounding the child, is key in treating children with anxiety. “In addition to biological risk, there is also an interacting influence of the child’s environment,” said lead author Kristie Poole, doctoral graduate student in the Department of Psychology, Neuroscience, Behaviour at McMaster University in Hamilton. “Clinicians must consider the context in which the child is residing, including both the family context as well as additional social contexts—so peers and school as well.” This may entail a more proactive approach when it comes to treating and, in turn, preventing child social anxiety. “For clinicians, if a parent does present with social anxiety disorder it is important to try to treat them because treatment may not only have a positive impact on the parent, it may also have the potential to improve things for the child, whether it is in terms of social anxiety or other diagnoses,” said co-author Dr. Ryan J. Van Lieshout, psychiatrist at the Women’s Health Concerns Clinic at St. Joseph’s Hospital and associate professor at the Department of Psychiatry and Behavioural Neurosciences at McMaster University.
SPEECH TASK METHOD A total of 112 children (57 males, 55 females) were observed over three visits spanning approximately three years. Their parents’ social anxiety was assessed using the Social Phobia and Anxiety Inventory. Children’s social anxiety was assessed at all three visits using the parent-reported Screen for Child Related Emotional Disorders (SCARED). A speech task was used to measure children’s behaviour and salivary cortisol reactivity. Children’s initial salivary cortisol levels were calcu-
lated during a baseline task. Then they had to deliver a speech about their most recent birthday while standing in front of a camera. They were told that other children would later watch their video. This was designed to induce social evaluative stress. About 15 minutes after the delivery of their speeches, researchers collected a second saliva sample to see if the children’s cortisol levels increased from baseline. Trajectories of child social anxiety were calculated through a growth curve analysis.
Dr. Van Lieshout
“Not every child of a socially anxious parent is going to develop social anxiety disorder,” said Dr. Van Lieshout. “We saw that it required both the cortisol reactivity and the social anxiety difficulties in the parents to produce clinically significant risk in the children.” HOW FACTORS INCREASE ANXIETY RISK Physiologically, there are some children who cannot regulate stress as well as others. This manifests in increased cortisol levels during stressors, according to the researchers. Furthermore, in this study parental social anxiety is considered as an environmental factor, as well as a genetic factor. That being said, it is important to note that there are multiple pathways to the development of social anxiety in children beyond cortisol reactivity and parental social anxiety. These are just two factors of many
that were examined in the present study, said Poole. For example, social modelling—where the parent displays socially anxious behaviours, inadvertently conveying to the child that social situations are fearful—can be one mechanism that explains why parental influences are so strong in these cases. “Maybe the parent is avoiding social situations . . . and the child may view their parents’ socially-anxious behaviours and then actually model their own behaviours in a similar way,” said Poole. Thus, children who already have a biological propensity for anxiety and are raised by guardians who are unable to teach them how to deal as effectively with stressors, are more likely to develop persistent social anxiety. “[These children] are at the greatest risk because they are not only prone to having poor physiological regulation, but they might also have less opportunities to engage in situations that may help to develop their social competence and confidence—key social skills that can lower social anxiety,” said Poole.
IMPLICATIONS FOR CURRENT TREATMENTS Although social anxiety can be caused by factors other than parental social anxiety, it can be recommended that clinicians implement treatments earlier and more aggressively in parents with social anxiety, in order to prevent diagnoses in their children. “We need to roll out more ways to try to manage the parent’s anxiety early on, because we know that early in life how the parent models his or her behaviour can influence the child,” said study co-author Louis A. Schmidt, PhD, director of the Child Emotion Laboratory and professor in the Department of Psychology, Neuroscience, and Behaviour at McMaster University. “The downstream effects of those interventions are ultimately going to influence the child’s behaviour. We can adjust and deal with it early in the process.” Proactive interventions can be taken in socially anxious patients with children but at this point, parental social anxiety and cortisol reactivity are not yet ready to be used for solid clinical predictions. “This is one of the first studies to show this . . . More work is needed before we can start to determine which children of socially anxious parents are at highest risk. Results need to be replicated,” said Dr. Van Lieshout. Following these children earlier and longer in life can also help determine whether parental social anxiety and cortisol reactivity levels are clinically relevant tests to apply in practice, added Dr. Schmidt.
August 2018 n 15
Copyright-free photo from pixabay.com via goo.gl/c4oMkk
by Bianca Quijano,
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Identifying risk factors for CTE and clinical presentations
n Neurodegenerative condition has no specific symptoms, more research needed for insight
by Louise Gagnon,
Correspondent, The Chronicle
ball or hockey or rugby would develop Cte if that were the case. “that doesn’t happen,” he said.
GENETICS AND CTE encephalopathy (Cte) continues to accumulate and is some of the unknowns that surround Cte, which had been suggesting that Cte is its own distinct entity, according referred to as dementia pugilistica and was thought to be limto the former assistant medical director at Burke rehabilitation ited to boxers, include factors which modify risk, according to dr. Jordan. “factors such as exposure [to repetitive brain trauHospital in white Plains, n.y. “Cte is probably a distinct neuropathological entity that ma], and genetic predisposition may modify risk [of developing Cte],” said dr. Jordan. is strongly associated with repetithe presence of apolipoprotive traumatic brain injury,” said tein e4 allele (apo e) has been dr. Barry d. Jordan, attending examined with respect to Cte. neurologist at Burke Factors such as early research involving 30 boxrehabilitation Hospital, the hosexposure [to repetitive ers had shown that possession of pital’s director of an aPoe epsilon4 allele may be neurorehabilitation and director brain trauma], and linked to heightened severity of of the Memory evaluation chronic neurologic deficits in genetic predisposition treatment service, and an associboxers who were deemed high ate professor of clinical neurolomay modify risk exposure, that is those who had gy at weill Medical College of participated in at least 12 or more [of developing CTE]. Cornell university. professional bouts (JAMA 1997; discussing Cte at the 2018 —Dr. Barry D. Jordan, attending neurologist, 278(2):136–140). rotman research institute Director of Neurorehabilitation, However, a recent study of Conference in late March in and Director of the Memory Evaluation college athletes from 23 different toronto—the theme of which Treatment Service at Burke Rehabilitation sites who participated in sports like was traumatic brain injury and Hospital in White Plains, N.Y. football, soccer, basketball, softconcussion—dr. Jordan noted ball, wrestling, and rugby found a that the definitive diagnosis of significant positive association between the presence of il-6r Cte is only made on autopsy. “the true prevalence is unknown,” said dr. Jordan, CC and the risk of concussion and a negative association explaining that Cte comes under the between the presence of aPoe4 and the risk of concussion. umbrella of chronic traumatic brain injury More specifically, il-6r CC was associated with a three-fold as do other conditions such as post-con- greater risk of concussion while aPoe4 was associated with cussion syndrome and chronic neurocogni- a 40% decreased risk (Br J Sports Med 2018; 52(3):192–198). tive impairment. ACCUMULATION OF TAU one early investigation of profession- depositions of phosphorylated tau have been identified in al boxers found 17% developed Cte after the brains of athletes who have been diagnosed with Cte, repetitive concussion or mild traumatic Dr. Jordan brain injury (J Neurol Neurosurg Psychiatry but the significance of these depositions remains unclear, explained dr. Jordan. “we need to determine the role of tau 1990; 53:373–378). in this disease,” he said.
CLINICAL PRESENTATION OF CTE dr. Jordan pointed to research that has described two variants of Cte, with one being a behaviour/mood variant that afflicts subjects at a younger age and the other being a cognitive variant that afflicts subjects at an older age (Neurology sept. 2013; 81(13):1122–1129). the symptoms of Cte are not specific, and there is no specific biomarker to make the diagnosis of Cte, noted dr. Jordan. in addition, there is overlap with other neurodegenerative diseases such as alzheimer’s disease and frontotemporal dementia (Curr Neurol Neurosci Rep 2015; 15(5):23). it has been observed that athletes who, in retrosepect, have been thought to have Cte experience periods in their life where they are symptom-free, noted dr. Jordan. repetitive brain trauma is not sufficient for the development of Cte, stressed dr. Jordan, noting that all athletes who experience repetitive brain trauma in contact sports like foot16 n August 2018
tau depositions are not unique to individuals with Cte; they have also been observed in individuals who have temporal lobe epilepsy (tle). research suggests the difference in the tau depositions between Cte brains and tle brains may lie in molecular weight: one analysis showed a Cte brain had high molecular weight tangle-associated tau while a brain with tle had low molecular weight tau (Brain Res 2016; 1630:225–240).
CONCLUSION advances in neuro-imaging are likely to provide more insights about Cte, highlighting what areas of the brain are most affected by the condition, according to dr. Jordan. neuropsychological testing should also be performed to detect if patients with Cte have deficits in cognition or motor skills, said dr. Jordan, noting patients with Cte can also have behavioural and mood disturbances, so clinicians need to be alert to detect those symptoms as well.
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Forecasting range of outcomes after concussion among pediatric patients
n Psychosocial factors such as home environment and even caregiver psychological distress can affect persistance of symptoms Correspondent, The Chronicle ultiPle
affect whether a child who has experienced a concussion will persist in having symptoms months afterward, according to the ronald and irene ward Chair in Pediatric Brain injury at the university of Calgary. during a presentation at the 2018 rotman research institute Conference in toronto in March, keith owen yeates, Phd, pointed out clinical advances have occurred with respect to appreciating the potential gravity of the impact of concussion on children.
IMPACT OF CONCUSSIONS “we used to think of concussion as a benign injury 20 years ago,” said dr. yeates, professor in the departments of Psychology, Pediatrics, and Clinical neurosciences at the university of Calgary. He also leads the university’s integrated Concussion research Program, the traumatic Brain injury neuroteam at the Hotchkiss Brain institute, and the Behaviour and the developing Brain theme at the alberta Children’s Hospital research institute. “although the majority of kids with concussions recover, there are really potential disastrous outcomes [due to concussion], and even some that are not quite so disastrous, but nonetheless have a significant impact on quality of life. Because it is such a common injury, even if only a small percentage of kids have persistent negative outcomes, it still represents a significant public health burden.” Dr. Yeates traumatic brain injury (tBi) is a major cause of pediatric morbidity and mortality, with more than 650,000 children experiencing head trauma resulting in hospital visits annually in the u.s. Concussion represents a burden to hospital emergency rooms, noted dr. yeates, adding that postinjury, families of pediatric patients may have to deal with a child’s motor problems, deficits in cognition, and behavioural challenges. FACTORS THAT AFFECT LINGERING SYMPTOMS Children can display a range of symptoms post-concussion, chief among them being headache, noted dr.
yeates. investigators have used tools such as the Health and Behavior inventory, which is available in a parent and child version, to gather information about various symptoms that are cognitive, somatic, emotional, and behavioural in nature from pediatric patients and their parents. dr. yeates has studied the effect of variables such as general family functioning, caregiver psychological distress, and home environment on long-term executive functioning subsequent to early childhood brain injury. He found that while home environment did not consistently predict executive functioning in the longterm, home environment affected group differences in executive functioning, in particular following complicated mild-to-moderate tBi (Int J Dev Neurosci May 2012; 30(3):231-237). specifically, the role of socio-economic status (ses) has been found to influence outcomes, such that children who come from a lower ses and have experienced mild tBi experience cognitive symptoms that persist out to 12 months, relative to children with mild tBi who come from a higher ses, according to dr. yeates. apart from injury severity and environmental characteristics, a child’s characteristics also can influence outcomes following a concussion, said dr. yeates. for instance, children with less effective coping skills
PREDICTING OUTCOMES in response to an absence of a clinical paradigm to predict the persistence of post-concussive symptoms, Canadian investigators participated in the 5P study (Predicting and Preventing Post-concussive Problems in Pediatrics), which involved nine Canadian pediatric emergency departments and employed a postconcussion symptom inventory. Patient symptoms were assessed at one, two, four, eight, and 12 weeks subsequent to injury (BMJ Open aug. 2013; 3(8)). study investigators collected information such as gender, age, prior history of concussion, the presence of migraine, and maintaining physical balance to generate a score that would predict the risk of persistence of symptoms after concussion. lower scores would mean a lower risk of persistent symptoms and higher scores would mean an increased risk, explained dr. yeates. still, a challenge remains in accurately estimating risk for the individual pediatric patient, said dr. yeates. “we need to get much better at individual predictions,” he said. “Providing group statistics does not help us to tell the patient’s [parent(s)] in front of us if their child will have persistent symptoms or not.” imaging data is also being incorporated in research undertakings to predict persistence of post-concussive symptoms, noted dr. yeates. More tools and scales are emerging to help refine risk prediction of symptoms. the Balance error scoring system (Bess) is used to assess balance, but other assessment tools such as the Center of Pressure (CoP) may detect balance deficits not captured by Bess (Orthop J Sports Med Mar. 2017; 5(3):2325967117695507). with the various data collected for the objective of prediction of symptoms after concussion in a given child, it is not likely that prediction will be achieved through something as simple as doing a blood test, said dr. yeates. “it won’t be reduced to a simple biomarker,” he said. “there are a lot of risk modifiers that include things like injury characteristics.” August 2018 n 17
Photo by Staff Sgt. Jim Araos (goo.gl/A3S5di) via U.S. Air Force
report more post-concussive symptoms (J Int Neuropsychol Soc Mar. 2011; 17(2):317-26).
by Louise Gagnon,
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“If the clinician, as observer, wishes to see things as they really are, he must make a tabula rasa of his mind and proceed without any preconceived notions whatsoever.”
—Dr. Jean-Martin Charcot, French neurologist (1825–1893)
Dr. Tom Feasby
Just named to the Order of Canada, the Albertabased leader in academic neurology is founder of an eminent stroke research and treatment program he former dean of the Cumming School of Medicine (CSM) at the University of Calgary, Dr. Tom Feasby, has been named to the Order of Canada. He was the founder of the country’s leading stroke research and treatment program. He also established the Calgary Neuromuscular and ALS Clinics and helped found the O’Brien Institute for Public Health at the CSM with Dr. Tom Noseworthy. Dr. Feasby has published over 100 research papers throughout his career with his research supported by the CIHR and the Heart and Stroke Foundation of Canada. Recently, Dr. Feasby has directed his focus toward health services research, the analysis of how people obtain access to care and the overuse of healthcare interventions. He recently served as the CEO of the Airdrie & Area Health Benefits Co-op in Airdrie, Alta., a community-owned healthcare hub. The initiative empowers residents to own their health and to improve the health of the community overall by focussing on the social determinants of health. Dr. Feasby is now facilitating the Airdrie Mental Health Task Force, a community-led group that is planning for an improved approach to mental health problems in Airdrie. tHe CHroniCle’s Bianca Quijano spoke with Dr. Feasby about being named to the Order of Canada, his career, and his thoughts on the future of neurologic medicine.
How did you feel after finding out about being named to the Order of Canada? it was surprising and exciting. i’m honoured, of course. i feel humbled to be included amongst these outstanding Canadians.
Why did you decide to specialize in neurology and neuromuscular diseases? when i was a medical student i found the brain the most interesting organ. i also had a couple of interesting mentors—neurologists and other surgeons—who i found interesting. i used to go to their weekly rounds and that inspired me to consider going into neurology. there was a neurosurgeon named dr. dwight Parkinson in winnipeg when i was a medical student, and later a neurologist in toronto named dr. Bob lee who certainly had a major role in my choice of career. Bob really enjoyed what he did. He was very interested in his patients. i found him an excellent role model.
18 n August 2018
You have accomplished so much in your career. What achievement are you most proud of? one of the things i’m most proud of is starting the Calgary stroke Program in the mid 1990s. this was a time when we weren’t doing much for stroke. we decided that we had to make a big effort to be involved in stroke, even though there wasn’t at that point a lot of light at the end of the tunnel. we started the stroke program and i was the director in the beginning. then we recruited a key leader, dr. alastair Buchan from ottawa, and he built it into what i think is perhaps the best stroke program in the world.
What was it about stroke research and treatment at that time that made it such a pivotal era? stroke was a really prevalent problem, but we had this sense of despair that there was so little we could do for patients with stroke. it was a very discouraging business. in many places neurologists didn’t even look after stroke patients. we thought, we have to take some action in this. the first thing to do was to create a focus on stroke. Part of that was creating a stroke prevention clinic, getting involved in stroke clinical trials, and recruiting a leader for it. at that time, fortunately, it was found that tissue plasminogen activator (tPa), the clotbusting drug, was effective in at least a portion of people with acute stroke. that gave us a tool to work with. tremendous advances in imaging also developed during the 1990s and thereafter. all these factors together provided tools that made the stroke program fly. But the key ingredients were the people we recruited, starting with alastair Buchan.
What do you think are some novel research and developments in neurology? one area that is going to be really interesting is empowerment of patients with information technology. we all refer facetiously to dr. google right now, but it’s going to become a much more powerful technique. the watson computer, for instance, which can beat chess masters and Jeopardy! champions, is also going to be able to beat the diagnosticians in terms of diagnosing medical illness. we’re going to find a tremendous increase in the use of information technology. i think
it’s going to transform medicine.
What lead you into health services research? when i was at mid-career i took a sabbatical and worked at the rand Corporation in santa Monica, Calif., a non-profit that helps improve policy-making through research. i spent a year there learning how to do health services research. when i finished that, i came back to Calgary and pursued a career direction in health services research with a particular interest in the appropriateness of healthcare interventions and the overuse of healthcare interventions, because it’s a pervasive problem here in Canada. there are all kinds of things we do more than we should do. it’s as big a problem as underuse. for example, one of the studies we did was on Mri of the lumbar spine. almost half the Mris of the lumbar spine don’t need to be done (JAMA Intern Med May 2013; 173(9):823–825).
Can you provide some updates about the Airdrie Health Co-op’s projects, such as the health park design concept? the idea of the airdrie Health Co-op was to do something to improve the health of the community by working mostly upstream from the healthcare system. we know that the social determinants of health are responsible for about 70 per cent of health. the healthcare system itself is probably responsible for less than 25 per cent. i’ve gotten involved in mental health and helping to direct the mental health taskforce to improve the mental healthcare in the community. that’s a more recent offshoot that i’m working on. What advice would you like to share with your colleagues who are just starting their careers in neurology? neurology offers a tremendous wealth of opportunity, different areas of interest. i would encourage young people to pick an area of interest, focus on it to develop some expertise, and then run with it. once they get their hands dirty and really dig into a subject, they’ll find it fascinating and that will carry them forward.
—Who’s making a difference near you? Tell The Chronicle, so we can tell our readers. Write us at firstname.lastname@example.org
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TECFIDERA (dimethyl fumarate) is indicated as monother therapy for the treatmen nt of relapsing remitting g multiple sclerosis (RRMS) to reduce the frequency of clinical exac x erbations and to dela ay the progression of disability sability. Consult the product monograph at https://pdf.hres.ca/dpd_pm/00042726.PDF a DF for contraindicationss, warnings, precautions, adverse reactions, interactions, dosing, and conditions of clinicall use. The product monogr ograph is also available by contacting Biogen Canada Inc. at 1-866-35 59-2502. * Based on worldwide post-market data, accurate as of January 2018. Reference: 1. Biogen Inc. TECFIDERA Exposure Letter Confirmation for Data Through 30 January 2018. March, 2018.
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Dr. Richard Gladstone, Founding Editor, Dr. J.J. Warsh, Psychiatry Editor, Dr. Sarah A. Morrow, Editor, Neurology Editor, Dr. Roger S. McInt...
Published on Sep 13, 2018
Dr. Richard Gladstone, Founding Editor, Dr. J.J. Warsh, Psychiatry Editor, Dr. Sarah A. Morrow, Editor, Neurology Editor, Dr. Roger S. McInt...