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  • 1
    Online Resource
    Online Resource
    Cambridge University Press (CUP) ; 2021
    In:  Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques
    In: Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, Cambridge University Press (CUP)
    Abstract: Impact des lésions cérébrales vasculaires dans des cas de neuro-dégénération : le protocole de l’étude COMPASS-ND. Objectif : Décrire le rôle de la neuro-imagerie et celui d’autres méthodes dans l’évaluation de l’impact des lésions cérébrales vasculaires (LCV) dans des cas de neuro-dégénération, et ce, dans le cadre de l’étude Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND). Menée dans plusieurs établissements de santé du Canada, il s’agit d’une étude de cohorte longitudinale prospective ayant inclus des critères de fiabilité et de faisabilité appliqués aux 200 premiers participants. Méthodes : L’étude COMPASS-ND a inclus des individus atteints de la maladie d’Alzheimer (MA ; n = 150), de la maladie de Parkinson (MP), de démence à corps de Lewy (DCL ; n = 200), de démence mixte (DM ; n = 200), de troubles cognitifs légers (TCL ; n = 400), de TCL attribuables à un accident ischémique vasculaire de la région sous-corticale (TCL-V ; n = 200), de troubles cognitifs subjectifs (TCS ; n = 300) ainsi qu’un groupe de témoins âgés en santé sur le plan cognitif ( n = 660). À noter que nos IRM ont été acquises selon le Protocole canadien d’imagerie de la démence (PCID) et ont été ensuite passées en revue visuellement en double aveugle par l’un ou l’autre de nos évaluateurs expérimentés en ce qui concerne les caractéristiques cliniques en jeu. D’autres évaluations pertinentes ont inclus l’historique de maladie vasculaire des individus à l’étude de même que leurs facteurs de risque, leur pression artérielle, leur taille et leur poids, leur taux de cholestérol, de glucose et d’hémoglobine A1c. Résultats : Des données analysables ont pu être obtenues chez 197 individus sur 200. Sur ces 197 individus, on en a diagnostiqué 18 avec des TCL-V ou une forme de démence mixte. La prévalence générale des infarctus s’est établie à 24,9 % ; celle des microhémorragies du cerveau à 24,6 % ; et celle des hyper-intensités de la matière blanche à 31,0 %. Les preuves par IRM d’un potentiel impact des LCV en matière de neuro-dégénération ont été observées chez 12,9 à 40,0 % des individus chez qui l’on avait diagnostiqué cliniquement une autre condition médicale que la MA. Enfin, soulignons que la fiabilité inter-évaluateurs s’est avérée bonne à excellente. Conclusion : Le protocole de l’étude COMPASS-ND s’est révélé une plate-forme utile pour se pencher sur les LCV et sur leurs liens avec certains facteurs de risque, biomarqueurs et tendances à un déclin cognitif et fonctionnel dans le cas de multiples maladies neurodégénératives liées au vieillissement. Des premiers résultats montrent à cet égard que les LCV décrites par IRM sont communes à tous les syndromes cognitifs et ne sont pas suffisamment reconnues sur le plan clinique.
    Type of Medium: Online Resource
    ISSN: 0317-1671 , 2057-0155
    RVK:
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2577275-2
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 1 ( 2022-01), p. 45-52
    Abstract: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. Methods: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. Results: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26–115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack ( P 〈 0.001), modified Rankin Scale score 〉 0 ( P 〈 0.001), and current tobacco use ( P =0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. Conclusions: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02313909.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 3
    In: Journal of Alzheimer's Disease, IOS Press, Vol. 81, No. 4 ( 2021-06-15), p. 1663-1671
    Abstract: Background: Cerebral amyloid angiopathy (CAA) contributes to brain neurodegeneration and cognitive decline, but the relationship between these two processes is incompletely understood. Objective: The purpose of this study is to examine cortical thickness and its association with cognition and neurodegenerative biomarkers in CAA. Methods: Data were collected from the Functional Assessment of Vascular Reactivity study and the Calgary Normative Study. In total, 48 participants with probable CAA, 72 cognitively normal healthy controls, and 24 participants with mild dementia due to AD were included. Participants underwent an MRI scan, after which global and regional cortical thickness measurements were obtained using FreeSurfer. General linear models, adjusted for age and sex, were used to compare cortical thickness globally and in an AD signature region. Results: Global cortical thickness was lower in CAA compared to healthy controls (mean difference (MD) –0.047 mm, 95% confidence interval (CI) –0.088, –0.005, p = 0.03), and lower in AD compared to CAA (MD –0.104 mm, 95% CI –0.165, –0.043, p = 0.001). In the AD signature region, cortical thickness was lower in CAA compared to healthy controls (MD –0.07 mm, 95% CI –0.13 to –0.01, p = 0.02). Within the CAA group, lower cortical thickness was associated with lower memory scores (R2 = 0.10; p = 0.05) and higher white matter hyperintensity volume (R2 = 0.09, p = 0.04). Conclusion: CAA contributes to neurodegeneration in the form of lower cortical thickness, and this could contribute to cognitive decline. Regional overlap with an AD cortical atrophy signature region suggests that co-existing AD pathology may contribute to lower cortical thickness observed in CAA.
    Type of Medium: Online Resource
    ISSN: 1387-2877 , 1875-8908
    Language: Unknown
    Publisher: IOS Press
    Publication Date: 2021
    detail.hit.zdb_id: 2070772-1
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  • 4
    In: BMJ Open, BMJ, Vol. 10, No. 8 ( 2020-08), p. e038120-
    Abstract: A number of MRI methods have been proposed to be useful, quantitative biomarkers of neurodegeneration in ageing. The Calgary Normative Study (CNS) is an ongoing single-centre, prospective, longitudinal study that seeks to develop, test and assess quantitative magnetic resonance (MR) methods as potential biomarkers of neurodegeneration. The CNS has three objectives: first and foremost, to evaluate and characterise the dependence of the selected quantitative neuroimaging biomarkers on age over the adult lifespan; second, to evaluate the precision, variability and repeatability of quantitative neuroimaging biomarkers as part of biomarker validation providing proof-of-concept and proof-of-principle; and third, provide a shared repository of normative data for comparison to various disease cohorts. Methods and analysis Quantitative MR mapping of the brain including longitudinal relaxation time (T1), transverse relaxation time (T2), T2*, magnetic susceptibility (QSM), diffusion and perfusion measurements, as well as morphological assessments are performed. The Montreal Cognitive Assessment (MoCA) and a brief, self-report medical history will be collected. Mixed regression models will be used to characterise changes in quantitative MR biomarker measures over the adult lifespan. In this report, we describe the study design, strategies to recruit and perform changes to the acquisition protocol from inception to 31 December 2018, planned statistical approach and data sharing procedures for the study. Ethics and dissemination Participants provide signed informed consent. Changes in quantitative MR biomarkers measured over the adult lifespan as well as estimates of measurement variance and repeatability will be disseminated through peer-reviewed scientific publication.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2599832-8
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  • 5
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 17 ( 2023-4-17)
    Abstract: Cerebral amyloid angiopathy (CAA) is a small vessel disease that causes covert and symptomatic brain hemorrhaging. We hypothesized that persons with CAA would have increased brain iron content detectable by quantitative susceptibility mapping (QSM) on magnetic resonance imaging (MRI), and that higher iron content would be associated with worse cognition. Methods Participants with CAA ( n = 21), mild Alzheimer’s disease with dementia (AD-dementia; n = 14), and normal controls (NC; n = 83) underwent 3T MRI. Post-processing QSM techniques were applied to obtain susceptibility values for regions of the frontal and occipital lobe, thalamus, caudate, putamen, pallidum, and hippocampus. Linear regression was used to examine differences between groups, and associations with global cognition, controlling for multiple comparisons using the false discovery rate method. Results No differences were found between regions of interest in CAA compared to NC. In AD, the calcarine sulcus had greater iron than NC (β = 0.99 [95% CI: 0.44, 1.53], q & lt; 0.01). However, calcarine sulcus iron content was not associated with global cognition, measured by the Montreal Cognitive Assessment ( p & gt; 0.05 for all participants, NC, CAA, and AD). Discussion After correcting for multiple comparisons, brain iron content, measured via QSM, was not elevated in CAA compared to NC in this exploratory study.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2411902-7
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  • 6
    In: Pattern Recognition Letters, Elsevier BV, ( 2023-8)
    Type of Medium: Online Resource
    ISSN: 0167-8655
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1466342-9
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  • 7
    In: NMR in Biomedicine, Wiley
    Abstract: T1‐weighted magnetization‐prepared rapid gradient‐echo (MPRAGE) is commonly included in brain studies for structural imaging using magnitude images; however, its phase images can provide an opportunity to assess microbleed burden using quantitative susceptibility mapping (QSM). This potential application for MPRAGE‐based QSM was evaluated using in vivo and simulated measurements. Possible factors affecting image quality were also explored. Detection sensitivity was evaluated against standard multiecho gradient echo (MEGE) QSM using 3‐T in vivo data of 15 subjects with a combined total of 108 confirmed microbleeds. The two methods were compared based on the microbleed size and susceptibility measurements. In addition, simulations explored the detection sensitivity of MPRAGE‐QSM at different representative magnetic field strengths and echo times using microbleeds of different size, susceptibility, and location. Results showed that in vivo microbleeds appeared to be smaller (× 0.54) and of higher mean susceptibility (× 1.9) on MPRAGE‐QSM than on MEGE‐QSM, but total susceptibility estimates were in closer agreement (slope: 0.97, r 2 : 0.94), and detection sensitivity was comparable. In simulations, QSM at 1.5 T had a low contrast‐to‐noise ratio that obscured the detection of many microbleeds. Signal‐to‐noise ratio (SNR) levels at 3 T and above resulted in better contrast and increased detection. The detection rates for microbleeds of minimum one‐voxel diameter and 0.4‐ppm susceptibility were 0.55, 0.80, and 0.88 at SNR levels of 1.5, 3, and 7 T, respectively. Size and total susceptibility estimates were more consistent than mean susceptibility estimates, which showed size‐dependent underestimation. MPRAGE‐QSM provides an opportunity to detect and quantify the size and susceptibility of microbleeds of at least one‐voxel diameter at B 0  of 3 T or higher with no additional time cost, when standard T 2 *‐weighted images are not available or have inadequate spatial resolution. The total susceptibility measure is more robust against sequence variations and might allow combining data from different protocols.
    Type of Medium: Online Resource
    ISSN: 0952-3480 , 1099-1492
    Language: English
    Publisher: Wiley
    Publication Date: 2024
    detail.hit.zdb_id: 2002003-X
    detail.hit.zdb_id: 1000976-0
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  • 8
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 17 ( 2023-4-17)
    Abstract: Previous reports have suggested that patients with cerebral amyloid angiopathy (CAA) may harbor smaller white matter, basal ganglia, and cerebellar volumes compared to age-matched healthy controls (HC) or patients with Alzheimer’s disease (AD). We investigated whether CAA is associated with subcortical atrophy. Methods The study was based on the multi-site Functional Assessment of Vascular Reactivity cohort and included 78 probable CAA (diagnosed according to the Boston criteria v2.0), 33 AD, and 70 HC. Cerebral and cerebellar volumes were extracted from brain 3D T1-weighted MRI using FreeSurfer (v6.0). Subcortical volumes, including total white matter, thalamus, basal ganglia, and cerebellum were reported as proportion (%) of estimated total intracranial volume. White matter integrity was quantified by the peak width of skeletonized mean diffusivity. Results Participants in the CAA group were older (74.0 ± 7.0, female 44%) than the AD (69.7 ± 7.5, female 42%) and HC (68.8 ± 7.8, female 69%) groups. CAA participants had the highest white matter hyperintensity volume and worse white matter integrity of the three groups. After adjusting for age, sex, and study site, CAA participants had smaller putamen volumes (mean differences, −0.024% of intracranial volume; 95% confidence intervals, −0.041% to −0.006%; p  = 0.005) than the HCs but not AD participants (−0.003%; −0.024 to 0.018%; p  = 0.94). Other subcortical volumes including subcortical white matter, thalamus, caudate, globus pallidus, cerebellar cortex or cerebellar white matter were comparable between all three groups. Conclusion In contrast to prior studies, we did not find substantial atrophy of subcortical volumes in CAA compared to AD or HCs, except for the putamen. Differences between studies may reflect heterogeneity in CAA presenting syndromes or severity.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2411902-7
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  • 9
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Journal of the American Heart Association Vol. 11, No. 19 ( 2022-10-04)
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 19 ( 2022-10-04)
    Abstract: Gait is a complex task requiring coordinated efforts of multiple brain networks. To date, there is little evidence on whether gait is altered in cerebral amyloid angiopathy (CAA). We aimed to identify impairments in gait performance and associations between gait impairment and neuroimaging markers of CAA, cognition, and falls. Methods and Results Gait was assessed using the Zeno Walkway during preferred pace and dual task walks, and grouped into gait domains (Rhythm, Pace, Postural Control, and Variability). Participants underwent neuropsychological testing and neuroimaging. Falls and fear of falling were assessed through self‐report questionnaires. Gait domain scores were standardized and analyzed using linear regression adjusting for age, sex, height, and other covariates. Participants were patients with CAA (n=29), Alzheimer disease with mild dementia (n=16), mild cognitive impairment (n=24), and normal elderly controls (n=47). CAA and Alzheimer disease had similarly impaired Rhythm, Pace, and Variability, and higher dual task cost than normal controls or mild cognitive impairment. Higher Pace score was associated with better global cognition, processing speed, and memory. Gait measures were not correlated with microbleed count or white matter hyperintensity volume. Number of falls was not associated with gait domain scores, but participants with low fear of falling had higher Pace (odds ratio [OR], 2.61 [95% CI, 1.59–4.29] ) and lower Variability (OR, 1.64 [95% CI, 1.10–2.44]). Conclusions CAA is associated with slower walking, abnormal rhythm, and greater gait variability than in healthy controls. Future research is needed to identify the mechanisms underlying gait impairments in CAA, and whether they predict future falls.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2653953-6
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  • 10
    In: International Journal of Stroke, SAGE Publications, Vol. 17, No. 7 ( 2022-08), p. 799-805
    Abstract: Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. Aims To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies. Methods At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression. Results Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52–1.7). Conclusions Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide. Registration: https://www.clinicaltrials.gov . Unique identifier: NCT 02313909
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2211666-7
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