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. ; https://doi.org/10. 1101 /2020 Simon Ducharme: Study concept and design, interpretation of the data, revising the manuscript. D. ...doi:10.1101/2020.11.25.398305 fatcat:nbetbwow4rcazo2b3fjqwzmqem
ABSTRACTObjectiveTo objectively quantify how cerebral volume loss could assist with clinical diagnosis and clinical trial design in the behavioural variant of frontotemporal dementia (bvFTD).MethodsWe applied deformation-based morphometric analyses with robust registration to precisely quantify the magnitude and pattern of atrophy in patients with bvFTD as compared to cognitively normal controls (CNCs), to assess the progression of atrophy over one year follow up and to generate clinical trialdoi:10.1101/670646 fatcat:z6u3hzdmcfdajhyivzmgrst47u
more »... ample size estimates to detect differences for the structures most sensitive to change. This study included 203 subjects - 70 bvFTD and 133 CNCs - with a total of 482 timepoints from the Frontotemporal Lobar Degeneration Neuroimaging Initiative.ResultsDeformation based morphometry (DBM) revealed significant atrophy in the frontal lobes, insula, medial and anterior temporal regions bilaterally in bvFTD subjects compared to controls with outstanding subcortical involvement. We provide detailed information on regional changes per year. In both cross-sectional analysis and over a one-year follow-up period, ventricle expansion was the most prominent differentiator of bvFTD from controls and a sensitive marker of disease progression.ConclusionsAutomated measurement of ventricular expansion is a sensitive and reliable marker of disease progression in bvFTD to be used in clinical trials for potential disease modifying drugs, as well as possibly to implement in clinical practice. Ventricular expansion measured with DBM provides the lowest published estimated sample size for clinical trial design to detect significant differences over one and two years.
To review the current evidence on buprenorphine-naloxone for the treatment of opioid-related disorders, with a focus on primary care settings. MEDLINE and the Cochrane Database of Systematic Reviews were searched. Evidence is mainly level I. Buprenorphine is a partial μ-opioid agonist and κ-opioid antagonist with a long half-life and less abuse potential than methadone. For detoxification, buprenorphine is at least equivalent to methadone and is superior to clonidine. For maintenance treatment,pmid:22267618 pmcid:PMC3264008 fatcat:gy3uecbjxfglxja65hqitcsawa
more »... buprenorphine is clearly superior to placebo. Methadone has a slight advantage in terms of retention in treatment, but a stepped approach with initial use of buprenorphine-naloxone is as efficacious. Use of buprenorphine in the primary care setting is feasible, safe, and effective. Authorization to prescribe buprenorphine can be obtained after completing online training. Buprenorphine is a safe and effective agent for detoxification from opioids. It can be used as a first-line agent in maintenance programs, owing to its lower abuse potential relative to other opioids. Its effectiveness in primary care settings makes it a useful therapeutic tool for family physicians.
Ducharme receives salary funding from the Fonds de Recherche du Québec -Santé. Dr. Ducharme is the co-founder of Arctic Fox AI (brain analytics). ...doi:10.1016/j.nicl.2019.102079 pmid:31795051 pmcid:PMC6879994 fatcat:kry2suqygnbzxokewbvs4rbucq
ABSTRACT:Objectives: To evaluate the attitudes and perceptions of psychiatrists and psychiatry residents regarding neurosurgical procedures for treating psychiatric disorders and to identify potential barriers to patient referral. Methods: A survey consisting of 25 questions was created using SurveyMonkey and was distributed to psychiatrists and psychiatry residents in Quebec. The study was approved by the McGill University Health Center's Research Ethics Board. Descriptive statistics anddoi:10.1017/cjn.2019.5 pmid:30975240 fatcat:ynganiclijglfjwe532hphhize
more »... an's test were performed using SPSS software. Results: A total of 99 participants, including 64 residents and 35 psychiatrists, completed more than 75% of the survey and were included in data analysis. Overall, participants were significantly (p < 0.0005) more comfortable in referring patients suffering from treatment-resistant obsessive–compulsive disorder than from treatment-resistant major depressive disorder and preferred to refer patients for deep brain stimulation (DBS) rather than for anterior cingulotomy/capsulotomy (AC). Only 11.43% of psychiatrists had ever referred a patient for AC or DBS, and 34.69% of respondents felt that these procedures were dangerous. Lack of knowledge (82.83%) was viewed as the principal limiting factor, and 57.58% of respondents identified ≥6 different barriers to patient referral. The majority of participants (69.39%) were interested in improving their knowledge on psychiatric neurosurgery, and 82.65% felt that this subject should be included in the psychiatry residency curriculum. Conclusion: Overall, participants acknowledged having many limitations to referring patients for neurosurgical interventions. While informative conferences discussing neuromodulation/neuroablation could easily address many barriers, further studies are required to assess how these could change attitudes and patterns of referral.
Simon Ducharme: Conceptualization, Methodology, Validation. Alan Evans: Funding acquisition, Supervision. Mallar M. ... After excluding problematic outputs, we then applied the same quality control procedure used by Ducharme et al. (2016) . ...doi:10.1016/j.neuroimage.2021.117974 pmid:33766753 fatcat:df62c6zbmjgrtp65wcmy2yllhe
Ducharme receives salary funding from the Fonds de Recherche du Québec-Santé. This project was not supported by a research grant. ... diagnosis of FTD currently poses a significant challenge for clinicians as the presenting symptoms overlap considerably with other diseases including primary psychiatric disorders and other dementias (Ducharme ...doi:10.1016/j.nicl.2018.08.028 pmid:30218900 pmcid:PMC6140291 fatcat:e3sidwg75nbyxkcahz3vuxk5vq
Predicting cognitive decline and the eventual onset of dementia in patients with Mild Cognitive Impairment (MCI) is of high value for patient management and potential cohort enrichment in pharmaceutical trials. We used cognitive scores and MRI biomarkers from a single baseline visit to predict the onset of dementia in an MCI population over a nine-year follow-up period. Method: All MCI subjects from ADNI1, ADNI2, and ADNI-GO with available baseline cognitive scores and T1w MRI were included indoi:10.1101/567867 fatcat:xf6tfz25vrgdjmqixliyuwckju
more »... he study (n=756). We built a Naive Bayes classifier for every year over a 9-year follow-up period and tested each one with Leave one out cross validation. Results: We reached 87% prediction accuracy at five years follow-up with an AUC>0.85 from two to seven years (peaking at 0.92 at five years). Both cognitive test scores and MR biomarkers were needed to make the prognostic models highly sensitive and specific, especially for longer follow-ups. MRI features are more sensitive, while cognitive features bring specificity to the prediction. Conclusion: Combining cognitive scores and MR biomarkers yield accurate prediction years before onset of dementia. Such a tool may be helpful in selecting patients that would most benefit from lifestyle changes, and eventually early treatments that would slow cognitive decline and delay the onset of dementia.
Investigation: Océane Ducharme, Stéphane Simon, Marine Ginouves, Ghislaine Prévot, Romain Blaizot. Methodology: Magalie Demar, Romain Blaizot. Resources: Ghislaine Prévot. ... Writing -original draft: Océane Ducharme. Writing -review & editing: Magalie Demar, Romain Blaizot. ...doi:10.1371/journal.pntd.0008380 pmid:32797078 fatcat:fin6jcisnrdnjhx7v3p2ilr7uq
INTRODUCTION: Heterogeneity in the progression of Alzheimer's disease makes it challenging to predict the rate of cognitive and functional decline for individual patients. Tools for short-term prediction could help enrich clinical trial designs and focus prevention strategies on the most at-risk patients. METHOD: We built a prognostic model using baseline cognitive scores and MRI-based features to determine which subjects with mild cognitive impairment remained stable and which functionallyarXiv:2101.08346v1 fatcat:hkgltqqrnrghthuephsqwxmojy
more »... ined (measured by a two-point increase in CDR-SB) over 2 and 3-year follow-up periods, periods typical of the length of clinical trials. RESULTS: Combining both sets of features yields 77% accuracy (81% sensitivity and 75% specificity) to predict cognitive decline at 2 years (74% accuracy at 3 years with 75% sensitivity and 73% specificity). Using this tool to select trial participants yields a 3.8-fold decrease in the required sample size for a 2-year study (2.8-fold decrease for a 3-year study) for a hypothesized 25% treatment effect to reduce cognitive decline. DISCUSSION: This cohort enrichment tool could accelerate treatment development by increasing power in clinical trials.
Testosterone is thought to play a crucial role in mediating sexual differentiation of brain structures. Examinations of the cognitive effects of testosterone have also shown beneficial and potentially sex-specific effects on executive function and mnemonic processes. Yet these findings remain limited by an incomplete understanding of the critical timing and brain regions most affected by testosterone, the lack of documented links between testosterone-related structural brain changes anddoi:10.1016/j.psyneuen.2016.12.005 pmid:27984812 pmcid:PMC5272813 fatcat:zlrnswknivc4tcvwcfs5w7uuia
more »... n, and the difficulty in distinguishing the effects of testosterone from those of related sex steroids such as of estradiol and dehydroepiandrosterone (DHEA). Here we examined associations between testosterone, cortico-hippocampal structural covariance, executive function (Behavior Rating Inventory of Executive Function) and verbal memory (California Verbal Learning Test-Children's Version), in a longitudinal sample of typically developing children and adolescents 6-22 yo, controlling for the effects of estradiol, DHEA, pubertal stage, collection time, age, handedness, and total brain volume. We found prefrontal-hippocampal covariance to vary as a function of testosterone levels, but only in boys. Boys also showed a specific association between positive prefrontal-hippocampal covariance (as seen at higher testosterone levels) and lower performance on specific components of executive function (monitoring the action process and flexibly shifting between actions). We also found the association between testosterone and a specific aspect of executive function (monitoring) to be significantly mediated by prefrontalhippocampal structural covariance. There were no significant associations between testosteronerelated cortico-hippocampal covariance and verbal memory. Taken together, these findings highlight the developmental importance of testosterone in supporting sexual differentiation of the brain and sex-specific executive function.
Annals of Neurology
To examine the relationship between carotid atherosclerosis and cerebral cortical thickness and investigate whether cortical thickness mediates the association between carotid atheroma and relative cognitive decline.doi:10.1002/ana.25324 pmid:30179274 pmcid:PMC6328248 fatcat:3g2ndkfaljby5fd6jum2o44g2i
Background/Aims: This study examines the longitudinal effect of metabolic syndrome (MetS) on brain-aging indices among cognitively normal (CN) and amnestic mild cognitive impairment (aMCI) groups [single-domain aMCI (saMCI) and multiple-domain aMCI (maMCI)]. Methods: The study population included 739 participants (CN = 226, saMCI = 275, and maMCI = 238) from the Alzheimer's Disease Neuroimaging Initiative, a clinic-based, multicenter prospective cohort. Confirmatory factor analysis was employeddoi:10.1159/000363285 pmid:25337075 pmcid:PMC4187257 fatcat:zoauo52itvcspjhsrmgfjuy74q
more »... to determine a MetS latent composite score using baseline data of vascular risk factors. We examined the changes of two Alzheimer's disease (AD) biomarkers, namely [ 18 F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) regions of interest and medial temporal lobe volume over 5 years.
Lateral ventricles are reliable and sensitive indicators of brain atrophy and disease progression in behavioral variant frontotemporal dementia (bvFTD). Here we validate our previously developed automated tool using ventricular features (known as VentRa) for the classification of bvFTD vs a mixed cohort of neurodegenerative, vascular, and psychiatric disorders from a clinically representative independent dataset. Methods: Lateral ventricles were segmented for 1110 subjects - 14 bvFTD, 30 otherdoi:10.1101/2022.03.29.22273096 fatcat:zqk4i6xadzbnbopf5kxvazzjyu
more »... rontotemporal Dementia (FTD), 70 Lewy Body Disease (LBD), 898 Alzheimer Disease (AD), 62 Vascular Brain Injury (VBI) and 36 Primary Psychiatric Disorder (PPD) from the publicly accessible National Alzheimers Coordinating Center dataset to assess the performance of VentRa. Results: Using ventricular features to discriminate bvFTD subjects from PPD, VentRa achieved an accuracy of 84%, 71% sensitivity and 89% specificity. VentRa was able to identify bvFTD from a mixed age-matched cohort (i.e., Other FTD, LBD, AD, VBI and PPD) and to correctly classify other disorders as not compatible with bvFTD with a specificity of 83%. The specificity against each of the other individual cohorts were 80% for other FTD, 83% for LBD, 83% for AD and 84% for VBI. Discussion: VentRa is a robust and generalizable tool with potential usefulness for improving the diagnostic certainty of bvFTD, particularly for the differential diagnosis with PPD.
Development of a successful research program can seem daunting when looked at from the starting line. It will take years if not decades to succeed and become sustainable. It requires local partnerships and mentoring; it mandates the establishment of review boards; it requires national health policies to allow for protected time for research in salaries and for fund granting agencies to be set up; it requires training of researchers and support staff as well as a change in the mindset ofdoi:10.1016/j.afjem.2020.09.005 pmid:33304799 pmcid:PMC7718449 fatcat:4xpy3zqetneldergwfjtl4aeku
more »... staff on the floor. It will almost inevitably require international support of some kind for low- and middle-income country researchers, be it university programs or other academic or private institutions. Success can occur; most likely it will occur by partnering with local research experts outside of emergency medicine in some combination with international networks and mentoring. Perhaps the most critical elements to success are intellectual curiosity and a burning flame of passion - and neither of those carry a financial cost.
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