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Introduction by the Convenors
THE INFLUENCE OF PRIOR COMORBIDITY AND MULTIMORBIDITY ON THE RISK OF POST-STROKE DEMENTIA: A META-ANALYSIS AND POPULATION-BASED STUDY
Abstract
Group Name
The Oxford Vascular Study
Background And Aims
Post-stroke dementia (PSD) is a highly prevalent after transient ischaemic attack and stroke. However, aetiology and prediction remain uncertain.
Methods
First, a systematic review (SR) and meta-analysis (MA) was performed to identify comorbidities previously associated with PSD. Second, the population-based Oxford Vascular Study (OXVASC) was used to examine associations between individual comorbidities or multimorbidity (defined as 2+ comorbidities identified from SR or the Charlson Comorbidity Index (CCI)) and PSD. Crude and adjusted (age and sex) odds ratios (ORs) were obtained by logistic regression.
Results
28 studies reported data on comorbidity status at stroke/TIA onset and PSD on follow up. Based on pooled estimates, PSD was predicted by hypertension (28 studies; OR 1.27 95%CI 1.14–1.43), diabetes (26 studies; OR 1.49 95%CI 1.32-1.68), atrial fibrillation (18 studies; OR 1.90 95%CI 1.64-2.20), ischaemic heart disease (15 studies; OR 1.20 95%CI 1.01-1.42), and peripheral vascular disease (8 studies; OR 2.09 95%CI 1.54-2.83), but not by hyperlipidaemia (12 studies; OR 0.71 95%CI 0.60-0.83). While crude estimates in OXVASC were largely similar, only diabetes remained significant after adjustment (ORadjusted 1.59 95%CI 1.16 - 2.17). Patients with multimorbidity, using either cardiovascular comorbidities identified by SR or the CCI, had greater odds of PSD compared to those without comorbidities (ORcrude 2.07, 95%CI 1.54-2.77 and ORcrude 1.38 95%CI 1.07-1.78, respectively).
Conclusions
Cardiovascular multimorbidity may help predict patients at greater risk of PSD, and diabetes appears to be a key aetiological risk factor for PSD.
Trial Registration Number
Not applicable
ASSOCIATIONS OF CHRONIC KIDNEY DISEASE WITH DEMENTIA BEFORE AND AFTER TRANSIENT ISCHEMIC ATTACK AND STROKE: POPULATION-BASED COHORT STUDY
Abstract
Group Name
on behalf of the Oxford Vascular Study
Background And Aims
Individuals with chronic kidney disease (CKD) appear to be at increased risk of cognitive impairment, with both vascular and neurodegenerative mechanisms postulated. To explore the vascular hypothesis, we studied the association between CKD and dementia before and after TIA and stroke.
Methods
In a prospective, population-based cohort study of TIA and stroke (Oxford Vascular Study; 2002-2012), pre-event and new post-event dementia were ascertained through direct patient assessment and follow-up for 5 years. Associations between pre-event dementia and CKD were examined using logistic regression, and between post-event dementia and CKD using Cox and competing risk regression models, adjusted for age, sex, education, stroke severity, prior stroke, white matter disease, diabetes mellitus, and dysphasia.
Results
Among 2305 TIA/stroke patients, 1174 (50.9%) had CKD. CKD was associated with both pre-event (odds ratio [OR], 2.04 [95% CI, 1.52–2.72]; P<0.001) and post-event dementia (hazard ratio [HR], 2.01 [95% CI, 1.65–2.44]; P<0.001), but these associations attenuated after adjustment for covariates (OR=0.92 [0.65-1.31]; p=0.65 and HR=1.09 [0.85-1.39]; p=0.50). The results were similar when a competing risk model was used (subdistribution HR [SHR] =1.74 [1.43-2.12; p<0.001, attenuating to 1.01 [0.78-1.33]; p=0.92 with adjustment). CKD was more strongly associated with late (>1 year) post-event dementia (SHR=2.32, 1.70-3.17; p<0.001), particularly after TIA and minor stroke (SHR=3.08, 2.05-4.64; p<0.001), but not significantly so after adjustment (SHR=1.53, 0.90-2.60; p=0.12).
Conclusions
In patients with TIA and stroke, CKD was not independently associated with either pre- or post-event dementia, suggesting that renal-specific mechanisms are unlikely to play an important role in aetiology.
Trial Registration Number
Not applicable
DOMAIN-SPECIFIC PREVALENCE OF PERSISTENT COGNITIVE IMPAIRMENT IN STROKE SURVIVORS: AN INTRODUCTION TO THE OX-CHRONIC STUDY OF LONG-TERM PSYCHOLOGICAL CONSEQUENCES OF STROKE
Abstract
Background And Aims
Understanding the long-term cognitive consequences of stroke is a vital but neglected part of providing effective care for stroke patients. With the advent of stroke specific cognitive screening (e.g. Oxford Cognitive Screen, OCS) it is becoming clear that solely screening for general cognitive impairment overlooks crucial domain-specific impairments in stroke patients. In order to capture the full long-term picture, it is crucial we also understand the domain-specific trajectories and describe the prevalence of persistent domain impairments post-stroke.
Methods
Cognitive profiles of 458 stroke survivors (216 female, mean age 74 years) were examined using the OCS during acute recovery (<2 weeks) and six-month later. We investigated the rates of individuals suffering persistent cognitive impairments (i.e. impaired during acute recovery and remained impaired after six months).
Results
Persistent impairment after six-months was most common for tests related to aphasia (e.g. for picture naming 43% and sentence reading 35% remain impaired). For memory impairments, 24-27% remained impaired while executive function remained impaired in 20% of participants. The tests with the lowest rates of persistent impairment was a measure of semantic understanding at 4%, followed by basic arithmetic ability (15%).
Conclusions
Many domain-specific impairments improve, but a significant number of people have lasting impairments. Examining the prevalence of persistent domain-specific impairments highlights the need to better understand the challenges for individuals recovering from stroke. We argue that there is a clear need for domain-specific assessments in order to tailor interventions and support to the individual needs of patients.
GRAPHICAL MODELLING OF THE INDEPENDENT ASSOCIATIONS BETWEEN DOMAINS SPECIFIC COGNITIVE IMPAIRMENTS IN SUBACUTE STROKE PATIENTS
Abstract
Background And Aims
Cognitive impairments are highly prevalent after stroke, often with multiple domain impairments presenting simultaneously. It remains to be understood how deficits in different cognitive functions interact with each other. For example, are impairments in domain general functions such as executive functions more likely to impact the overall cognitive profile compared to domain specific impairments in e.g. spatial attention. A Graphical modelling approach established a network of associations, with metrics of centrality denoting the relative strength of connections between specific domain tests.
Methods
Participants were sub-acute stroke survivors recruited for three separate studies, two in the UK and one in Italy. In total 1035 participants (452 Female, mean age = 70.8 years) were included in analyses. Cognitive domains were assessed using 11 subtests from the Oxford Cognitive Screen and binarized into impaired vs. unimpaired. The Bootnet R package was used to apply an isofit model the binary data. Bootstrapping was used to assess graph stability and compare the expected influence of each test.
Results
Figure 1 shows the resulting cognitive impairment network. The mixed trails test (a measure of executive function) had the highest expected influence. It was significantly stronger than the expected influence for tests of episodic memory, praxis, semantic knowledge, and visual spatial neglect. However, the expected influence of the trails test was not significantly higher than that for language processing, number processing, or orientation. 
Conclusions
These results provide evidence that impairments in executive functions and language have a large negative impact on other cognitive domains.
THE EFFECT OF MULTIDOMAIN INTERVENTIONS TARGETING CARDIOVASCULAR RISK FACTORS ON GLOBAL COGNITION, DEPRESSION AND APATHY – A POOLED ANALYSIS OF TWO RANDOMIZED CONTROLLED TRIALS
Abstract
Group Name
On behalf of the preDIVA and MAPT/DSA groups
Background And Aims
Cardiovascular risk factors and lifestyle factors are associated with an increased risk of cognitive decline and dementia in observational studies. We pooled individual participant data from two multi-domain intervention trials on cognitive function and symptoms of depression to increase power and facilitate subgroup analyses.
Methods
We used individual participant data from preDIVA and MAPT, two multidomain intervention trials focusing on cardiovascular and lifestyle related risk factors in community-dwelling, non-demented individuals, or care as usual. Crude scores on cognitive functioning (Mini Mental State Examination [MMSE]) and symptoms of depression and apathy (15-item Geriatric Depression Scale) collected at baseline, 2 and 3-4 years of follow-up were analyzed using linear mixed models. Prespecified subgroup analyses were performed for sex, educational level, baseline MMSE<26, history of hypertension, cardiovascular disease and study.
Results
We included 4162 individuals (median age 74 years, IQR 72, 76) with a median follow-up duration of 3.7 years (IQR 3.0 to 4.1 years). No differences between intervention and control groups were observed on change in scores for cognitive functioning and symptoms of depression and apathy. The MMSE declined less in the intervention groups in those with MMSE<26 at baseline (N=250; MD=0.84; 95%CI=0.15 -1.54; p<0.001).
Conclusions
We found no conclusive evidence that multidomain interventions targeting cardiovascular risk factors reduce the risk of global cognitive decline, symptoms of depression or apathy in a mixed older population. These interventions may be more effective in those with lower baseline cognitive functioning. Extended follow-up for dementia occurrence is important to inform on the potential long-term effects of multidomain interventions.
CLINICAL RELEVANCE OF CORTICAL CEREBRAL MICROINFARCTS ON 1.5T MRI IN THE LATE-ADULT POPULATION
Abstract
Background And Aims
Cortical cerebral microinfarcts (CMIs) have been linked with dementia and impaired cognition in cross-sectional studies. However, the clinical relevance of CMIs in a population-based setting is lacking. We examine the association of CMIs detected on 1.5T MRI with cardiovascular factors, cerebrovascular disease, and brain-tissue volumes. We further explore their association with cognitive decline and risk of stroke, dementia, and mortality in general-population.
Methods
2156 participants with clinical history and baseline MRI were included. CMIs were graded based on a previously-validated method. Markers of cerebrovascular disease and brain tissue volumes were assessed on MRI. Cognition was assessed using a detailed neuropsychological test at baseline and at five years of follow-up. Data on incident stroke, dementia, and mortality were included until January 2016.
Results
227 individuals (10.5%) had ≥1 cortical CMIs. The major risk factors of cortical CMIs were male sex, current smoking, history of heart disease, and stroke. Furthermore, presence of cortical CMIs was associated with infarcts and smaller brain volume. Persons with cortical CMIs showed cognitive decline in Stroop Tests. During a mean follow-up of 5.2 years, 73 (4.3%) individuals developed incident stroke, 95 (5.1%) incident dementia, and 399 (19.2%) died. People with cortical CMIs were at an increased risk of stroke (HR:1.18,95%CI:1.09-1.28) and mortality (HR:1.09,95%CI:1.00-1.19).
Conclusions
Cortical CMIs are highly prevalent in a population-based setting and are associated with cardiovascular disease, cognitive decline and increased risk of stroke and mortality. Future investigations will have to show whether cortical CMIs are a useful biomarker to intervene upon to reduce the burden of stroke.
Trial Registration Number
NA
PROGRESSION OF CEREBRAL SMALL VESSEL DISEASE AND THE VERY LONG-TERM RISK OF DEMENTIA
Abstract
Background And Aims
The number of dementia cases is expected to triple the next decades. SVD is the most important vascular contributor to dementia and may constitute an early modifiable treatment target. We aimed to investigate the relation between SVD burden and progression, and incident dementia during a 14 years follow-up.
Methods
We included 503 participants with sporadic SVD from the prospective RUN DMC study. In 2006, 2011, 2015 and 2020 patients underwent a standardized MRI-protocol and cognitive assessments. Progression of SVD was analyzed between 2006 and 2011. Dementia adjudication (based on DSM IV criteria ) was done multidisciplinary until December 9, 2020. Cumulative dementia risk was estimated using Kaplan-Meier analysis. The relation between baseline and progression of SVD-burden and incident dementia was analyzed with cox regression models.
Results
Of 498 patients with available dementia endpoint, 108 patients (21.5%) developed dementia during median follow-up of 14.0 years. Impaired microstructural integrity (PSMD) and WMH volumes were associated with incident dementia (Figure 1). In the multivariable regression model, presence of DWI+ lesions (2.29 [1.11-4.75]; P = 0.03) was associated with all-cause dementia. PSMD was specifically associated with vascular dementia. After adjustment for demographic and vascular risk factors, WMH progression (1.23 per 1-SD increase [1.02-1.48]; P = 0.03) was significantly associated with incident dementia, however not after adjustment for hippocampus atrophy rate.
Conclusions
We reveal that SVD-markers on MRI are associated with very long-term dementia outcomes in SVD patients. They can be considered an early risk factor for late life dementia, with now potential treatments available.
SEX DIFFERENCES IN OCCURRENCE AND TYPE OF POST-STROKE COGNITIVE IMPAIRMENT: A MULTICENTER STUDY IN 2950 PATIENTS WITH ACUTE ISCHEMIC STROKE
Abstract
Background And Aims
Post-stroke cognitive impairment (PSCI) occurs in about half of stroke survivors. It is unknown if occurrence and type of PSCI within a year after ischemic stroke differs by sex.
Methods
We harmonized individual patient data from twelve cohorts through the Meta-VCI-Map consortium. Patients with acute symptomatic infarcts on CT/MRI and cognitive assessment <1 year post-stroke were eligible. PSCI was defined as impairment in ≥1 cognitive domains on neuropsychological assessment or impairment on the Montreal Cognitive Assessment, both based on local norm-referenced data. Odds ratios (OR) for PSCI and the separate cognitive domains were calculated with logistic regression analyses.
Results
2950 patients (age 67±12 years, 39% female) were analyzed. Females were older (69 ±12 versus 65±11 years; p<.001) and lower educated (71% <high school versus 49%; p<.001) than males. The risk of PSCI was comparable between the sexes (males OR 0.94 (95%CI 0.81-1.09)), 45% of females and 43% of males. Females had a higher risk of impairment in the domains attention & executive functioning (males OR 0.75 (95%CI 0.60-0.94)), and language (males OR 0.67 (95%CI 0.53-0.83)), whereas males had a higher risk of verbal memory impairment (males OR 1.31 (95%CI1.08-1.59)). The risk of impairment in the other domains, information processing speed; visuospatial perception/construction; and visuospatial memory was comparable between the sexes.
Conclusions
PSCI is equally common in both females and males, but PSCI cognitive profiles differ by sex. This has implications for post-stroke clinical care, since both the diagnosis and rehabilitation are influenced by cognitive profile.
Trial Registration Number
Not applicable