Krista L Lanctôt

Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

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Publications (221)955.79 Total impact

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    ABSTRACT: Every year, approximately 62 000 people with stroke and transient ischemic attack are treated in Canadian hospitals, and the evidence suggests one-third or more will experience vascular-cognitive impairment, and/or intractable fatigue, either alone or in combination. The 2015 update of the Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue Module guideline is a comprehensive summary of current evidence-based recommendations for clinicians in a range of settings, who provide care to patients following stroke. The three consequences of stroke that are the focus of the this guideline (poststroke depression, vascular cognitive impairment, and fatigue) have high incidence rates and significant impact on the lives of people who have had a stroke, impede recovery, and result in worse long-term outcomes. Significant practice variations and gaps in the research evidence have been reported for initial screening and in-depth assessment of stroke patients for these conditions. Also of concern, an increased number of family members and informal caregivers may also experience depressive symptoms in the poststroke recovery phase which further impact patient recovery. These factors emphasize the need for a system of care that ensures screening occurs as a standard and consistent component of clinical practice across settings as stroke patients transition from acute care to active rehabilitation and reintegration into their community. Additionally, building system capacity to ensure access to appropriate specialists for treatment and ongoing management of stroke survivors with these conditions is another great challenge. © 2015 World Stroke Organization.
    International Journal of Stroke 06/2015; DOI:10.1111/ijs.12557 · 4.03 Impact Factor
  • Value in Health 05/2015; 18(3):A228-A229. DOI:10.1016/j.jval.2015.03.1329 · 2.89 Impact Factor
  • A. Li, B. Paes, I. Mitchell, K. Lanctôt
    Value in Health 05/2015; 18(3):A232-A233. DOI:10.1016/j.jval.2015.03.1353 · 2.89 Impact Factor
  • Value in Health 05/2015; 18(3):A231. DOI:10.1016/j.jval.2015.03.1343 · 2.89 Impact Factor
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    ABSTRACT: Current treatments for Alzheimer's disease (AD) provide modest symptomatic relief but do not slow the progression of the disease. Latrepirdine may modulate several targets involved in AD pathology, including lipid peroxidation, mitochondrial permeability, voltage-gated calcium ion channels as well as neurotransmitter receptor activity, and thus potentially represents both a symptomatic and disease-modifying intervention. Several randomized, placebo-controlled trials have sought to evaluate the effect of latrepirdine on cognition, function and behaviour in patients with AD. To evaluate the efficacy and safety of latrepirdine for the treatment of AD. We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 4 June 2014 using the terms: latrepirdine OR dimebon OR dimebolin OR 2,3,4,5-tetrahydro-2,8-dimethyl-5- (2-(6-methyl-3-pyridyl)ethyl)-1H-pyrido(4,3-b)indole. We included all randomized, double-blind, placebo-controlled trials where latrepirdine was administered to patients with mild, moderate or severe AD. We assessed the quality of studies and two authors extracted data. We calculated mean difference (MD), risk ratio (RR) and 95% confidence interval (CI) on an intention-to-treat (ITT) basis for all relevant outcome measures. Seven trials involving a total of 1697 participants were found and six were included in the quantitative analyses. No data were available from the seventh trial. Three trials involving 1243 patients were included in analyses of efficacy outcomes, and four trials involving 1034 patients were included in analyses of safety and tolerability outcomes. We judged five trials to be at high risk of bias due to selective outcome reporting and three to be at high risk of attrition bias. There was low quality evidence favouring latrepirdine on the Clinician's Interview - Based Impression of Change Plus Caregiver Input after 26 weeks (CIBIC-Plus) (MD -0.60, 95% CI -0.89 to -0.31, 1 study, P < 0.001). Due to imprecision in the results, it was not possible to determine whether latrepirdine had any effect on cognition measured with the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) (MD -1.49, 95% CI -3.47 to 0.49, 3 studies, P = 0.14) or the Mini-Mental State Examination (MMSE) (MD 0.59, 95% CI -0.94 to 2.11, 3 studies, P = 0.45), or on function measured with the Alzheimer's Disease Co-operative Study - Activities of Daily Living scale (ADCS-ADL) (MD 1.00, 95% CI -1.15 to 3.15, 3 studies, P = 0.36) at study endpoint (26 or 52 weeks). We considered the evidence provided on these outcomes to be of overall low quality. However, there was some high quality evidence showing a very small benefit of latrepirdine on the Neuropsychiatric Inventory (NPI) (MD -1.77, 95% CI -3.09 to -0.45, 3 studies, P = 0.009) at study endpoint (26 or 52 weeks). Additionally, moderate quality evidence suggested that latrepirdine and placebo were comparable in adverse events (RR 1.03, 95% CI 0.93 to 1.14, P = 0.51), serious adverse events (RR 0.86, 95% CI 0.55 to 1.35, P = 0.52), dropouts (RR 0.91, 95% CI 0.65 to 1.27, P = 0.57) and dropouts due to adverse events (RR 0.98, 95% CI 0.57 to 1.67, P = 0.93). Our meta-analysis is limited by the small number of studies, imprecision, inconsistencies between studies and likelihood of bias. Nevertheless, the evidence to date suggests that while not associated with an increased risk of adverse events compared with placebo, there is no effect of latrepirdine on cognition and function in mild-to-moderate AD patients, though there appears to be a modest benefit for behaviour. Further studies should investigate the potential benefit of latrepirdine on neuropsychiatric symptoms in AD.
    Cochrane database of systematic reviews (Online) 04/2015; 4:CD009524. DOI:10.1002/14651858.CD009524.pub2 · 5.94 Impact Factor
  • American Journal of Geriatric Psychiatry 03/2015; 23(3):S172-S173. DOI:10.1016/j.jagp.2014.12.181 · 3.52 Impact Factor
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    ABSTRACT: Severe aortic stenosis is the most common valvular heart disease in the elderly in the Western world and contributes to a large proportion of all deaths over the age of 70. Severe aortic stenosis is conventionally treated with surgical aortic valve replacement; however, the less invasive transcatheter aortic valve implantation (TAVI) is suggested for those at high surgical risk. While TAVI has been associated with improved survival and favourable outcomes, there is a higher incidence of cerebral microembolisms in TAVI patients. This finding is of concern given mechanistic links with cognitive decline, a symptom highly prevalent in those with cardiovascular disease. This paper reviews the literature assessing the possible link between TAVI and cognitive changes. Studies to date have shown that global cognition improves or remains unchanged over 3 months following TAVI while individual cognitive domains remain preserved over time. However, the association between TAVI and cognition remains unclear due to methodological limitations. Furthermore, while these studies have largely focused on memory, cognitive impairment in this population may be predominantly of vascular origin. Therefore, cognitive assessment focusing on domains important in vascular cognitive impairment, such as executive dysfunction, may be more helpful in elucidating the association between TAVI and cognition in the long term.
    Cardiovascular Psychiatry and Neurology 02/2015; 2015:1-8. DOI:10.1155/2015/209569
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    ABSTRACT: ABSTRACT Background: Agitation is common across neuropsychiatric disorders and contributes to disability, institutionalization, and diminished quality of life for patients and their caregivers. There is no consensus definition of agitation and no widespread agreement on what elements should be included in the syndrome. The International Psychogeriatric Association formed an Agitation Definition Work Group (ADWG) to develop a provisional consensus definition of agitation in patients with cognitive disorders that can be applied in epidemiologic, non-interventional clinical, pharmacologic, non-pharmacologic interventional, and neurobiological studies. A consensus definition will facilitate communication and cross-study comparison and may have regulatory applications in drug development programs. Methods: The ADWG developed a transparent process using a combination of electronic, face-to-face, and survey-based strategies to develop a consensus based on agreement of a majority of participants. Nine-hundred twenty-eight respondents participated in the different phases of the process. Results: Agitation was defined broadly as: (1) occurring in patients with a cognitive impairment or dementia syndrome; (2) exhibiting behavior consistent with emotional distress; (3) manifesting excessive motor activity, verbal aggression, or physical aggression; and (4) evidencing behaviors that cause excess disability and are not solely attributable to another disorder (psychiatric, medical, or substance-related). A majority of the respondents rated all surveyed elements of the definition as "strongly agree" or "somewhat agree" (68-88% across elements). A majority of the respondents agreed that the definition is appropriate for clinical and research applications. Conclusions: A provisional consensus definition of agitation has been developed. This definition can be used to advance interventional and non-interventional research of agitation in patients with cognitive impairment.
    International Psychogeriatrics 10/2014; 27(1):1-11. DOI:10.1017/S1041610214001963 · 1.89 Impact Factor
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    ABSTRACT: Objectives Coronary artery disease (CAD) is associated with an increased risk of cognitive decline. While cerebral white matter (WM) damage predicts cognitive function in CAD, conventional neuroimaging measures only partially explain the effect of CAD on cognition. The purpose of this study is to determine if white matter microstructural integrity and CAD using diffusion tensor imaging (DTI) correlates with cognitive function in older adults with CAD. Methods 49 CAD patients (66±7 years, 86% male) underwent neurocognitive assessments using the cognitive battery recommended by the National Institute of Neurological Disorders and Stroke–Canadian Stroke Network for the study of vascular cognitive impairment. Composite scores for each cognitive domain were calculated. Microstructural integrity in normal appearing WM was quantified as fractional anisotropy (FA) using DTI in 9 bilateral and 2 inter-hemispheric WM tracts from the Johns Hopkins University WM Tractography Atlas. Linear regression models examined associations between FA and cognitive performance, controlling for age, sex, and education, with correction for multiple comparisons using a false discovery rate of 5%. Results Executive function was most significantly associated with FA in the left parahippocampal cingulum (β=.471, t=3.381, df=44, p=.002) and left inferior fronto-occipital fasciculus (β=.430, t=2.984, df=44, p=.005). FA was not associated with memory in any of the WM tracts examined. Conclusions These results suggest that WM microstructural integrity may be an important neural correlate of executive function even in cognitively intact CAD patients. This study suggests WM damage may be relevant to subtle cognitive decline in a population that may have early neural risk for dementia.
    American Journal of Geriatric Psychiatry 09/2014; 23(7). DOI:10.1016/j.jagp.2014.09.008 · 3.52 Impact Factor
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    ABSTRACT: Depression is a commonly occurring and persistent sequel of stroke affecting approximately 29% of patients. An immunological hypothesis has been put forward, and synthesis of kynurenine from tryptophan has been proposed to link inflammatory activity with neurotoxicity and neurotransmitter dysfunction. This study assessed the relationship between peripheral blood kynurenine and poststroke depressive symptoms.
    Neuropsychiatric Disease and Treatment 09/2014; 10:1827-35. DOI:10.2147/NDT.S65740 · 2.15 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Arterial transit time is the time needed for blood to travel from large arteries to capillaries, as estimated from arterial spin-labeling MR imaging. The purpose of this study was to determine whether vascular risk factors and cognitive performance are related to regional differences in cerebral arterial transit time in patients with coronary artery disease who are at risk for cognitive decline. MATERIALS AND METHODS: Arterial transit time was estimated from multiple postlabel delay pseudocontinuous arterial spin-labeling images obtained from 29 men with coronary artery disease. Tests of memory, attention, processing speed, and executive function were administered. Principal component analysis was used to create separate models of cognition and vascular risk, which were related to brain regions through voxelwise analyses of arterial transit time maps. RESULTS: Principal component analysis identified 2 components of vascular risk: 1) "pressor" (age, systolic blood pressure, and pulse pressure) and 2) "obesity" (body fat percentage and body mass index). Obesity was inversely related to arterial transit time in the posterior cingulate, precuneus, lateral occipital cortices, middle temporal gyrus, and frontal pole (P corrected < .05), whereas pressor was not significant. Cognitive scores were factored into a single component. Poor performance was inversely related to precuneus arterial transit time (P corrected < .05). The average arterial transit time in regions identified by obesity was associated with poorer cognitive function (r(2) = 0.21, t = -2.65, P = .01). CONCLUSIONS: Altered cerebral hemodynamics, notably in nodal structures of the default mode network, may be one way that vascular risk factors impact cognition in patients with coronary artery disease.
    American Journal of Neuroradiology 08/2014; 36(2). DOI:10.3174/ajnr.A4094 · 3.68 Impact Factor
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    ABSTRACT: Despite widespread use of second-generation cholinesterase inhibitors for the symptomatic treatment of Alzheimer's disease (AD), little is known about the long term effects of cholinergic treatment on global cognitive function and potential specific effects in different cognitive domains. The objectives of this study were to determine the association between cholinergic treatment and global cognitive function over one and two years in a cohort of patients with mild or moderate AD and identify potential differences in domain-specific cognitive outcomes within this cohort. A cohort of patients meeting the revised National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for mild or moderate AD, including patients both on treatment with a cholinesterase inhibitor and untreated controls (treated = 65, untreated = 65), were recruited from the Cognitive Neurology Clinic at Sunnybrook Health Sciences Centre, as part of the Sunnybrook Dementia Study. Patients were followed for one to two years and underwent standardized neuropsychological assessments to evaluate global and domain-specific cognitive function. Associations between cholinesterase inhibitor use and global and domain-specific cognitive outcome measures at one and two years of follow-up were estimated using mixed model linear regression, adjusting for age, education, and baseline mini mental state examination (MMSE). At one year, treated patients showed significantly less decline in global cognitive function, and treatment and time effects across tests of executive and visuospatial function. At two years, there was a significant trend towards less decline in global cognition for treated patients. Moreover, treated patients showed significant treatment and time effects across tests of executive functioning, memory, and visuospatial function. The present study offers two important contributions to knowledge of the effectiveness of cholinesterase inhibitor treatment in patients with mild-moderate AD: 1) that second-generation cholinesterase inhibitors demonstrate long-term effectiveness for reducing global cognitive decline over one to two years of follow-up, and 2) that decline in function for cognitive domains, including executive function, memory, and visuospatial skill that are primarily mediated by frontal networks and by the cholinergic system, rather than memory, may be slowed by treatment targeting the cholinergic system.
    Alzheimer's Research and Therapy 08/2014; 6(4):48. DOI:10.1186/alzrt280 · 3.50 Impact Factor
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    ABSTRACT: Patients with coronary artery disease (CAD) are at risk of accelerated cognitive decline, particularly those with major depression. Mechanisms for cognitive deficits associated with CAD, and the effects of depression, remain poorly understood. However, CAD is associated with inflammatory processes that have been linked to neurodegeneration, may contribute to cognitive decline, and are elevated in depression. Platelet-activating factors (PAFs) are emerging as key lipid mediators that may be central to those processes and highly relevant to cognitive decline in CAD.
    Journal of Neuroinflammation 07/2014; 11(1):119. DOI:10.1186/1742-2094-11-119 · 4.90 Impact Factor
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    Alzheimer's and Dementia 07/2014; 10(4):P628. DOI:10.1016/j.jalz.2014.05.1093 · 17.47 Impact Factor
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    ABSTRACT: Stroke variably activates interleukin- (IL-) 17 expression, reduces regulatory T cells, and induces oxidative stress, which may support neurodegeneration. Ischemic stroke patients were screened for depressive symptoms (Center for Epidemiological Studies Depression (CES-D)) and cognitive status (Mini Mental State Examination). Proinflammatory cytokines (IL-17, IL-23, and interferon- [IFN-] γ), anti-inflammatory cytokine IL-10, and lipid hydroperoxide (LPH), a measure of oxidative stress, were assayed from fasting serum. Of 47 subjects (age 71.8 ± 14.4 years, 36% female), 19 had depressive symptoms (CES-D ≥ 16), which was associated with poorer cognitive status (F 1,46 = 8.44, P = 0.006). IL-17 concentrations did not differ between subjects with and without depressive symptoms (F 1,46 = 8.44, P = 0.572); however, IL-17 was associated with poorer cognitive status in subjects with depressive symptoms (F 1,46 = 9.29, P = 0.004). In those subjects with depressive symptoms, IL-17 was associated with higher LPH (ρ = 0.518, P = 0.023) and lower IL-10 (ρ = -0.484, P = 0.036), but not in those without. In conclusion, poststroke depressive symptoms may be associated with cognitive vulnerability to IL-17 related pathways, involving an imbalance between proinflammatory and anti-inflammatory activity and increased oxidative stress.
    BioMed Research International 06/2014; 2014:245210. DOI:10.1155/2014/245210 · 2.71 Impact Factor
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    ABSTRACT: Children with Down syndrome (DS) are at significant risk for respiratory syncytial virus (RSV) infection and related hospitalization. We compared hospitalization rates due to respiratory tract infection in children with DS aged <2 years who prospectively received palivizumab during the RSV season with a previously published, similar untreated DS birth cohort. A total of 532 children with DS who prospectively received palivizumab were assembled from the prospective Canadian RSV Evaluation Study of Palivizumab registry between 2005 and 2012. The untreated group included 233 children with DS derived from a nationwide Dutch birth cohort from 2003 to 2005. Events during the RSV seasons were counted. Poisson regression analysis was performed to compare incidence rate ratios (95% confidence intervals [CIs]) between groups while controlling for observation length and known risk factors for severe RSV infection. In total, 31 (23 untreated, 8 treated) RSV-related hospitalizations were documented. The adjusted risk of RSV-related hospitalizations was higher in untreated subjects than in palivizumab recipients (incidence rate ratio 3.63; 95% CI, 1.52-8.67). The adjusted risk of hospitalization for all respiratory tract infection (147 events; 73 untreated, 74 treated) was similar (incidence rate ratio untreated versus palivizumab 1.11; 95% CI, 0.80-1.55). These results suggest that palivizumab is associated with a 3.6-fold reduction in the incidence rate ratio for RSV-related hospitalization in children with DS during the first 2 years of life. A randomized trial is needed to determine the efficacy of RSV immunoprophylaxis in this specific high-risk patient population.
    PEDIATRICS 05/2014; 133(6). DOI:10.1542/peds.2013-3916 · 5.30 Impact Factor
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    ABSTRACT: Physical activity is associated with positive effects on the brain but there is a paucity of clinical neuroimaging data in patients with coronary artery disease (CAD), a cardiovascular condition associated with grey matter loss. The purpose of this study was to determine which brain regions are impacted by cardiopulmonary fitness and with the change in fitness after 6 months of exercise-based cardiac rehabilitation. CAD patients underwent magnetic resonance imaging at baseline, and peak volume of oxygen uptake during exercise testing (VO2Peak) was measured at baseline and after 6 months of training. T1-weighted structural images were used to perform grey matter (GM) voxel-based morphometry (VBM). Pseudo-continuous arterial spin labeling (pcASL) was used to produce cerebral blood flow (CBF) images. VBM and CBF data were tested voxel-wise using VO2Peak and age as explanatory variables. In 30 men with CAD (mean age 65±7 years), VBM and CBF identified 7 and 5 respective regions positively associated with baseline VO2Peak. These included the pre- and post-central, paracingulate, caudate, hippocampal regions and converging findings in the putamen. VO2Peak increased by 20% at follow-up in 29 patients (t = 9.6, df = 28, p<0.0001). Baseline CBF in the left post-central gyrus and baseline GM density in the right putamen predicted greater change in VO2Peak. Perfusion and GM density were associated with fitness at baseline and with greater fitness gains with exercise. This study identifies new neurobiological correlates of fitness and demonstrates the utility of multi-modal MRI to evaluate the effects of exercise in CAD patients.
    PLoS ONE 03/2014; 9(3):e91251. DOI:10.1371/journal.pone.0091251 · 3.53 Impact Factor
  • American Journal of Geriatric Psychiatry 03/2014; 22(3):S110. DOI:10.1016/j.jagp.2013.12.127 · 3.52 Impact Factor
  • Biological Psychiatry 01/2014; 77(3). DOI:10.1016/j.biopsych.2014.06.006 · 9.47 Impact Factor

Publication Stats

5k Citations
955.79 Total Impact Points

Institutions

  • 1995–2015
    • Sunnybrook Health Sciences Centre
      • Department of Psychiatry
      Toronto, Ontario, Canada
  • 1990–2015
    • University of Toronto
      • • Department of Psychiatry
      • • Department of Pharmacology and Toxicology
      • • Faculty of Medicine
      • • Sunnybrook Health Sciences Centre
      • • Division of Geriatric Psychiatry
      Toronto, Ontario, Canada
  • 2012
    • University of Oxford
      • Nuffield Department of Clinical Medicine
      Oxford, England, United Kingdom
  • 2009
    • Centre for Addiction and Mental Health
      Toronto, Ontario, Canada
  • 1989
    • Instituto de Investigación Clínica de Occidente
      Zapopan, Jalisco, Mexico