Browsing by Author "Black, Sandra E."

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    Characterizing Plasma Biomarkers of Cerebral Amyloid Angiopathy
    (2024-07-26) Muir, Ryan Thomas; Smith, Eric E.; Hill, Michael D.; Black, Sandra E.; Hsuing, Robin
    BACKGROUND: Cerebral Amyloid Angiopathy (CAA) is characterized by the progressive deposition of beta-amyloid in cortical and leptomeningeal small vessels leading to hemorrhagic stroke and dementia. While CAA is diagnosed using Boston Criteria 2.0, they are not always possible to apply. Plasma biomarkers (Aβ42, Aβ40, phosphorylated-tau (p-tau), neurofilament light chain (NfL) and Glial Fibrillary Acidic Protein (GFAP)) might improve diagnostic accuracy. This study evaluates whether plasma biomarkers: (i) differ in CAA compared to controls (ii) discriminate a diagnosis of CAA individually and in combination and (iii) are associated with cognition and neuroimaging biomarkers. METHODS: Data are from a multi-centre cohort study of participants with probable CAA and healthy controls. Participants had plasma collected and underwent neurocognitive evaluation and magnetic resonance imaging. Aβ was quantified with two independent methods: immunoprecipitation mass-spectrometry (IPMS) and single molecule array assay (Simoa). Plasma p-tau181, NfL and GFAP were quantified with Simoa. Neuroimaging biomarkers of small vessel disease, atrophy, white matter integrity and cerebrovascular reactivity (CVR) were quantified. Logistic regression was used to compute areas under the receiver operating characteristic curve (AUC) to assess biomarker discriminative performance of ascertaining a diagnosis of CAA. Associations between plasma biomarkers, cognition and neuroimaging biomarkers were evaluated with generalized linear models. RESULTS: 45 participants with CAA and 47 controls were eligible. With both methods, the Aβ42/40 ratio was reduced in CAA compared to controls. Furthermore, those with CAA had elevated p-tau181 and NfL. A combination of Aβ42/40 (Simoa), p-tau181, and NfL resulted in an AUC of 0.90. Reduced Aβ42/40 was associated with poorer speed of processing. Increasing NfL was associated with reduced Montreal Cognitive Assessment Scores, lower CVR and increasing CAA severity. CONCLUSIONS: This study identified differences in plasma Aβ42/40, p-tau181 and NfL in CAA compared and provides evidence that a panel of these biomarkers can achieve excellent diagnostic discriminability. This study also demonstrates that a marker of cerebral amyloidosis (Aβ42/40) is associated with speed of processing difficulties in those with CAA, while NfL was associated with global cognition, CAA severity and CVR. Overall, plasma biomarkers might, in future, help improve the evaluation and detection of CAA.
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    The impact of reporting magnetic resonance imaging incidental findings in the Canadian alliance for healthy hearts and minds cohort
    (2021-10-28) Luu, Judy M.; Sergeant, Anand K.; Anand, Sonia S.; Desai, Dipika; Schulze, Karleen; Knoppers, Bartha M.; Zawati, Ma’n H.; Smith, Eric E.; Moody, Alan R.; Black, Sandra E.; Larose, Eric; Marcotte, Francois; Kleiderman, Erika; Tardif, Jean-Claude; Lee, Douglas S.; Friedrich, Matthias G.
    Abstract Background In the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies. Methods Between 2013 and 2019, 8252 participants (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported. Results Severe structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy. Conclusion The management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT02220582 .
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    The Prevalence and Incidence of Dementia: a Systematic Review and Meta-analysis
    (CAMBRIDGE UNIV PRESS, 2016) Fiest, Kirsten M.; Jette, Nathalie; Roberts, Jodie I.; Maxwell, Colleen J.; Smith, Eric E.; Black, Sandra E.; Blaikie, Laura; Cohen, Adrienne; Day, Lundy; Holroyd-Leduc, Jayna; Kirk, Andrew; Pearson, Dawn; Pringsheim, Tamara; Venegas-Torres, Andres; Hogan, David B.
    Introduction: Dementia is a common neurological condition affecting many older individuals that leads to a loss of independence, diminished quality of life, premature mortality, caregiver burden and high levels of healthcare utilization and cost. This is an updated systematic review and meta-analysis of the worldwide prevalence and incidence of dementia. Methods: The MEDLINE and EMBASE databases were searched for relevant studies published between 2000 (1985 for Canadian papers) and July of 2012. Papers selected for full-text review were included in the systematic review if they provided an original population-based estimate for the incidence and/or prevalence of dementia. The reference lists of included articles were also searched for additional studies. Two individuals independently performed abstract and full-text review, data extraction, and quality assessment of the papers. Random-effects models and/or meta-regression were used to generate pooled estimates by age, sex, setting (i.e., community, institution, both), diagnostic criteria utilized, location (i.e., continent) and year of data collection. Results: Of 16,066 abstracts screened, 707 articles were selected for full-text review. A total of 160 studies met the inclusion criteria. Among individuals 60 and over residing in the community, the pooled point and annual period prevalence estimates of dementia were 48.62 (CI95%: 41.98-56.32) and 69.07 (CI95%: 52.36-91.11) per 1000 persons, respectively. The respective pooled incidence rate (same age and setting) was 17.18 (CI95%: 13.90-21.23) per 1000 person-years, while the annual incidence proportion was 52.85 (CI95%: 33.08-84.42) per 1,000 persons. Increasing participant age was associated with a higher dementia prevalence and incidence. Annual period prevalence was higher in North America than in South America, Europe and Asia (in order of decreasing period prevalence) and higher in institutional compared to community and combined settings. Sex, diagnostic criteria (except for incidence proportion) and year of data collection were not associated with statistically significant different estimates of prevalence or incidence, though estimates were consistently higher for females than males. Conclusions: Dementia is a common neurological condition in older individuals. Significant gaps in knowledge about its epidemiology were identified, particularly with regard to the incidence of dementia in low- and middle-income countries. Accurate estimates of prevalence and incidence of dementia are needed to plan for the health and social services that will be required to deal with an aging population.
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    White matter hyperintensities and smaller cortical thickness are associated with neuropsychiatric symptoms in neurodegenerative and cerebrovascular diseases
    (2023-06-20) Ozzoude, Miracle; Varriano, Brenda; Beaton, Derek; Ramirez, Joel; Adamo, Sabrina; Holmes, Melissa F.; Scott, Christopher J. M.; Gao, Fuqiang; Sunderland, Kelly M.; McLaughlin, Paula; Goubran, Maged; Kwan, Donna; Roberts, Angela; Bartha, Robert; Symons, Sean; Tan, Brian; Swartz, Richard H.; Abrahao, Agessandro; Saposnik, Gustavo; Masellis, Mario; Lang, Anthony E.; Marras, Connie; Zinman, Lorne; Shoesmith, Christen; Borrie, Michael; Fischer, Corinne E.; Frank, Andrew; Freedman, Morris; Montero-Odasso, Manuel; Kumar, Sanjeev; Pasternak, Stephen; Strother, Stephen C.; Pollock, Bruce G.; Rajji, Tarek K.; Seitz, Dallas; Tang-Wai, David F.; Turnbull, John; Dowlatshahi, Dar; Hassan, Ayman; Casaubon, Leanne; Mandzia, Jennifer; Sahlas, Demetrios; Breen, David P.; Grimes, David; Jog, Mandar; Steeves, Thomas D. L.; Arnott, Stephen R.; Black, Sandra E.; Finger, Elizabeth; Rabin, Jennifer; Tartaglia, Maria C.
    Abstract Background Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases. Methods Five hundred thirteen participants with one of these conditions, i.e. Alzheimer’s Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson’s Disease, or Cerebrovascular Disease, were included in the study. NPS were assessed using the Neuropsychiatric Inventory – Questionnaire and grouped into hyperactivity, psychotic, affective, and apathy subsyndromes. White matter hyperintensities were quantified using a semi-automatic segmentation technique and FreeSurfer cortical thickness was used to measure regional grey matter loss. Results Although NPS were frequent across the five disease groups, participants with frontotemporal dementia had the highest frequency of hyperactivity, apathy, and affective subsyndromes compared to other groups, whilst psychotic subsyndrome was high in both frontotemporal dementia and Parkinson’s disease. Results from univariate and multivariate results showed that various predictors were associated with neuropsychiatric subsyndromes, especially cortical thickness in the inferior frontal, cingulate, and insula regions, sex(female), global cognition, and basal ganglia-thalamus white matter hyperintensities. Conclusions In participants with neurodegenerative and cerebrovascular diseases, our results suggest that smaller cortical thickness and white matter hyperintensity burden in several cortical-subcortical structures may contribute to the development of NPS. Further studies investigating the mechanisms that determine the progression of NPS in various neurodegenerative and cerebrovascular diseases are needed.