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Importance: Risk of major stroke is high during the hours and days after transient ischemic attack (TIA) and minor stroke but is substantially reduced by urgent medical treatment. Public education campaigns have improved the response after major stroke, but their association with behavior after TIA and minor stroke is uncertain. The number of potentially preventable early recurrent strokes in patients who delay or fail to seek medical attention is unknown., Objective: To investigate the association of public education with delays and failure in seeking medical attention after TIA and minor stroke., Design, Setting, and Participants: Prospective population-based study of all patients with TIA or stroke who sought medical attention between April 1, 2002, and March 31, 2014, registered at 9 general practices in Oxfordshire, United Kingdom. Data analysis took place from July 1, 2013, to March 2, 2015., Exposures: Face, Arm, Speech, Time (FAST) public education campaign in the United Kingdom., Main Outcomes and Measures: Number of early recurrent strokes in patients who delayed or failed to seek medical attention, as well as the odds of seeking urgent attention after TIA and minor stroke before vs after initiation of the public education campaign., Results: Among 2243 consecutive patients with first TIA or stroke (mean [SD] age, 73.6 [13.4] years; 1126 [50.2%] female; 96.3% of white race/ethnicity), 1656 (73.8%) had a minor stroke or TIA. After the FAST campaign, patients with major stroke more often sought medical attention within 3 hours (odds ratio [OR], 2.56; 95% CI, 1.11-5.90; P = .03). For TIA and minor stroke, there was no improvement in use of emergency medical services (OR, 0.79; 95% CI, 0.50-1.23; P for interaction = .03 vs major stroke) or time to first seeking medical attention within 24 hours (OR, 0.75; 95% CI, 0.48-1.19; P for interaction = .006 vs major stroke). Patient perception of symptoms after TIA and minor stroke was associated with more urgent behavior, but correct perception declined after the FAST campaign (from 37.3% [289 of 774] to 27.6% [178 of 645]; OR, 0.64; 95% CI, 0.51-0.80; P < .001). One hundred eighty-eight patients had a stroke within 90 days of their initial TIA or stroke, of whom 93 (49.5%) followed unheeded TIAs for which no medical attention was sought, similar before and after the FAST campaign (43 of 538 [8.0%] before vs 50 of 615 [8.1%] after, P = .93)., Conclusions and Relevance: This study suggests that in contrast to major stroke, extensive FAST-based public education has not improved the response to TIA and minor stroke in the United Kingdom, emphasizing the need for campaigns that are tailored to transient and less severe symptoms.

Background and Purpose- Studies of causes of cerebral small vessel disease (SVD) should fully adjust for blood pressure (BP), but most etiological studies use a single BP measurement or history of hypertension, which might underestimate the role of hypertension. In patients with transient ischemic attack and ischemic stroke, we therefore compared the associations of baseline and long-term premorbid BP with measures of SVD on magnetic resonance imaging brain. Methods- We studied 1009 transient ischemic attack/ischemic stroke patients who had a brain magnetic resonance imaging, in the population-based OXVASC (Oxford Vascular Study), and related baseline and 20-year premorbid BP (median: 15 readings/patient) to the total SVD score on imaging. Results- SVD score was associated with increasing mean baseline systolic BP (SBP; odds ratio of top versus bottom BP quartile: 2.28; [95% CI, 1.62-3.21]; P<0.0001) and with prior hypertension (2.53; [95% CI, 2.01-3.20]; P<0.0001), but the association was much stronger with mean premorbid SBP (6.09; [95% CI, 4.34-8.55]; P<0.0001). Mean diastolic BP at baseline was negatively associated with SVD score (0.71; [95% CI, 0.51-1.00]; P=0.050), and a positive association was only evident for diastolic BP 10 to 20 years previously (3.35; [95% CI, 2.33-4.84]; both P<0.0001). Relationships between overall mean premorbid BP and SVD burden were strongest in patients age <70 (SBP: 6.99; 4.11-11.86; diastolic BP: 3.13; 1.95-5.07; both P<0.0001) versus ≥70 years (2.37; 1.42-3.94; P=0.001; and 1.16; 0.74-1.84; P=0.52). Conclusions- Mean premorbid SBP is more strongly associated with SVD burden than baseline SBP or history of hypertension, and baseline diastolic BP yields a misleading estimate of the likely etiological importance of midlife hypertension for the subsequent development of SVD. Studies of novel potential etiological factors for SVD should aim to adjust for long-term prior BP, and trials of BP lowering with only a few years of follow-up may underestimate the overall impact on SVD.

Objective: To determine the age-specific temporal trends in blood pressure (BP) before acute lacunar vs nonlacunar TIA and stroke., Methods: In a population-based study of TIA/ischemic stroke (Oxford Vascular Study), we studied 15-year premorbid BP readings from primary care records in patients with lacunar vs nonlacunar events (Trial of Org 10172 in Acute Stroke Treatment [TOAST]) stratified by age (<65, ≥65 years)., Results: Of 2,085 patients (1,250 with stroke, 835 with TIA), 309 had lacunar events. In 493 patients <65 years of age, the prevalence of diagnosed hypertension did not differ between lacunar and nonlacunar events (46 [48.4%] vs 164 [41.2%], p = 0.20), but mean/SD premorbid BP (44,496 BP readings) was higher in patients with lacunar events (15-year records: systolic BP [SBP] 138.5/17.7 vs 133.3/15.0 mm Hg, p = 0.004; diastolic BP [DBP] 84.1/9.6 vs 80.9/8.4 mm Hg, p = 0.001), mainly because of higher mean BP during the 5 years before the event (SBP 142.6/18.8 vs 134.6/16.6 mm Hg, p = 0.0001; DBP 85.2/9.7 vs 80.6/9.0 mm Hg, p < 0.0001), with a rising trend ( p trend = 0.006) toward higher BP leading up to the event (<30-day pre-event SBP: 152.7/16.1 vs 135.3/23.1 mm Hg, p = 0.009; DBP 87.9/9.4 vs 80.8/12.8 mm Hg, p = 0.05; mean BP ≤1 year before the event 145.8/22.0 vs 134.7/16.1 mm Hg, p = 0.001; 86.1/10.7 vs 80.4/9.8 mm Hg, p = 0.0001). Maximum BP in the 5 years before the event was also higher in patients with lacunar events (SBP 173.7/26.6 vs 158.6/23.2 mm Hg, p = 0.0001; DBP 102.3/12.9 vs 94.2/11.2 mm Hg, p < 0.0001), as was persistently elevated BP (≥50% SBP >160 mm Hg, odd ratio 4.95, 95% confidence interval 1.99-12.31, p = 0.0002). However, no similar differences in BP were observed in patients ≥65 years of age., Conclusion: Recent premorbid BP control is strongly temporarily related to acute lacunar events at younger ages, suggesting a direct role of BP in accelerating causal pathology and highlighting the need to control hypertension quickly., (Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Aspirin is recommended for secondary prevention after transient ischaemic attack (TIA) or ischaemic stroke on the basis of trials showing a 13% reduction in long-term risk of recurrent stroke. However, the risk of major stroke is very high for only the first few days after TIA and minor ischaemic stroke, and observational studies show substantially greater benefits of early medical treatment in the acute phase than do longer-term trials. We hypothesised that the short-term benefits of early aspirin have been underestimated., Methods: Pooling the individual patient data from all randomised trials of aspirin versus control in secondary prevention after TIA or ischaemic stroke, we studied the effects of aspirin on the risk and severity of recurrent stroke, stratified by the following time periods: less than 6 weeks, 6-12 weeks, and more than 12 weeks after randomisation. We compared the severity of early recurrent strokes between treatment groups with shift analysis of modified Rankin Scale (mRS) score. To understand possible mechanisms of action, we also studied the time course of the interaction between effects of aspirin and dipyridamole in secondary prevention of stroke. In a further analysis we pooled data from trials of aspirin versus control in which patients were randomised less than 48 h after major acute stroke, stratified by severity of baseline neurological deficit, to establish the very early time course of the effect of aspirin on risk of recurrent ischaemic stroke and how this differs by severity at baseline., Findings: We pooled data for 15,778 participants from 12 trials of aspirin versus control in secondary prevention. Aspirin reduced the 6 week risk of recurrent ischaemic stroke by about 60% (84 of 8452 participants in the aspirin group had an ischaemic stroke vs 175 of 7326; hazard ratio [HR] 0·42, 95% CI 0·32-0·55, p<0·0001) and disabling or fatal ischaemic stroke by about 70% (36 of 8452 vs 110 of 7326; 0·29, 0·20-0·42, p<0·0001), with greatest benefit noted in patients presenting with TIA or minor stroke (at 0-2 weeks, two of 6691 participants in the aspirin group with TIA or minor stroke had a disabling or fatal ischaemic stroke vs 23 of 5726 in the control group, HR 0·07, 95% CI 0·02-0·31, p=0·0004; at 0-6 weeks, 14 vs 60 participants, 0·19, 0·11-0·34, p<0·0001). The effect of aspirin on early recurrent ischaemic stroke was due partly to a substantial reduction in severity (mRS shift analysis odds ratio [OR] 0·42, 0·26-0·70, p=0·0007). These effects were independent of dose, patient characteristics, or aetiology of TIA or stroke. Some further reduction in risk of ischaemic stroke accrued for aspirin only versus control from 6-12 weeks, but there was no benefit after 12 weeks (stroke risk OR 0·97, 0·84-1·12, p=0·67; severity mRS shift OR 1·00, 0·77-1·29, p=0·97). By contrast, dipyridamole plus aspirin versus aspirin alone had no effect on risk or severity of recurrent ischaemic stroke within 12 weeks (OR 0·90, 95% CI 0·65-1·25, p=0·53; mRS shift OR 0·90, 0·37-1·72, p=0·99), but dipyridamole did reduce risk thereafter (0·76, 0·63-0·92, p=0·005), particularly of disabling or fatal ischaemic stroke (0·64, 0·49-0·84, p=0·0010). We pooled data for 40,531 participants from three trials of aspirin versus control in major acute stroke. The reduction in risk of recurrent ischaemic stroke at 14 days was most evident in patients with less severe baseline deficits, and was substantial by the second day after starting treatment (2-3 day HR 0·37, 95% CI 0·25-0·57, p<0·0001)., Interpretation: Our findings confirm that medical treatment substantially reduces the risk of early recurrent stroke after TIA and minor stroke and identify aspirin as the key intervention. The considerable early benefit from aspirin warrants public education about self-administration after possible TIA. The previously unrecognised effect of aspirin on severity of early recurrent stroke, the diminishing benefit with longer-term use, and the contrasting time course of effects of dipyridamole have implications for understanding mechanisms of action., Funding: Wellcome Trust, the National Institute of Health Research (NIHR) Biomedical Research Centre, Oxford., (Copyright © 2016 Rothwell et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Vascular dementia is the second most common form of dementia but reliable evidence on age-specific associations between blood pressure (BP) and risk of vascular dementia is limited and some studies have reported negative associations at older ages., Methods: In a cohort of 4.28 million individuals, free of known vascular disease and dementia and identified from linked electronic primary care health records in the United Kingdom (Clinical Practice Research Datalink), we related BP to time to physician-diagnosed vascular dementia. We further determined associations between BP and dementia in a prospective population-based cohort of incident transient ischemic attack and stroke (Oxford Vascular Study)., Results: For a median follow-up of 7.0 years, 11 114 initial presentations of vascular dementia were observed in the primary care cohort after exclusion of the first 4 years of follow-up. The association between usual systolic BP and risk of vascular dementia decreased with age (hazard ratio per 20 mm Hg higher systolic BP, 1.62; 95% confidence interval, 1.13-2.35 at 30-50 years; 1.26, 1.18-1.35 at 51-70 years; 0.97, 0.92-1.03 at 71-90 years; P trend=0.006). Usual systolic BP remained predictive of vascular dementia after accounting for effect mediation by stroke and transient ischemic attack. In the population-based cohort, prior systolic BP was predictive of 5-year risk of dementia with no evidence of negative association at older ages., Conclusions: BP is positively associated with risk of vascular dementia, irrespective of preceding transient ischemic attack or stroke. Previous reports of inverse associations in old age could not be confirmed., (© 2016 American Heart Association, Inc.)

Background and Purpose: Cognitive assessment is recommended after stroke but there are few data on the applicability of short cognitive tests to the full spectrum of patients. We therefore determined the rates, causes, and associates of untestability in a population-based study of all transient ischemic attack (TIA) and stroke., Methods: Patients with TIA or stroke prospectively recruited (2002-2007) into the Oxford Vascular Study had ≥1 short cognitive test (mini-mental state examination, telephone interview of cognitive status, Montreal cognitive assessment, and abbreviated mental test score) at baseline and on follow-up to 5 years., Results: Among 1097 consecutive assessed survivors (mean: age/SD, 74.8/12.1 years; 378 TIA), numbers testable with a short cognitive test at baseline, 1, 6, 12, and 60 months were 835/1097 (76%), 778/947 (82%), 756/857 (88%), 692/792 (87%), and 472/567 (83%). Eighty-eight percent (331/378) of assessed patients with TIA were testable at baseline compared with only 46% (133/290) of major stroke (P<0.001). Untestability was also associated with older age, premorbid dependency, death on follow-up, and with both pre- and postevent dementia (all P<0.01). Untestability (and problems with testing) were commonly caused by acute stroke effects at baseline (153/262 [58%]: dysphasia/anarthria/hemiparesis=84 [32%], drowsiness=58 [22%], and acute confusion=11 [4%]), whereas sensory deficits caused relatively more problems with testing at later time points (24/63 [38%] at 5 years)., Conclusions: Substantial numbers of patients with TIA and stroke are untestable with short cognitive tests. Future studies should report data on untestable patients and those with problems with testing in whom the likelihood of dementia is high., (© 2015 American Heart Association, Inc.)

Background and Purpose: Copeptin, the c-terminal portion of provasopressin, is a useful prognostic marker in patients after myocardial infarction and heart failure. More recently, high levels of copeptin have also been associated with worse functional outcome and increased mortality within the first year after ischemic stroke and transient ischemic attack (TIA). However, to date, there are no published data on whether copeptin predicts long-term risk of vascular events after TIA and stroke., Methods: We measured copeptin levels in consecutive patients with TIA or ischemic stroke in a population-based study (Oxford Vascular Study) recruited from 2002 to 2007 and followed up to 2014. Associations with risk of recurrent vascular events were determined by Cox-regression., Results: During ≈6000 patient-years in 1076 patients, there were 357 recurrent vascular events, including 174 ischemic strokes. After adjustment for age, sex, and risk factors, copeptin was predictive of recurrent vascular events (adjusted hazard ratio per SD, 1.47; 95% confidence interval, 1.31-1.64; P=0.0001), vascular death (1.85; 1.60-2.14; P<0.0001), all-cause death (1.75; 1.58-1.93; P<0.0001), and recurrent ischemic stroke (1.22; 1.04-1.44; P=0.017); and improved model-discrimination significantly: net reclassification improvement for recurrent vascular events (32%; P<0.0001), vascular death (55%; P<0.0001), death (66%; P<0.0001), and recurrent stroke (16%; P=0.044). The predictive value of copeptin was largest in patients with cardioembolic index events (adjusted hazard ratio, 1.84; 95% confidence interval, 1.53-2.20 versus 1.31, 1.14-1.50 in noncardioembolic stroke; P=0.0025). In patients with cardioembolic stroke, high copeptin levels were associated with a 4-fold increased risk of vascular events within the first year of follow-up (adjusted hazard ratio, 4.02; 95% confidence interval, 2.13-7.70)., Conclusions: In patients with TIA and ischemic stroke, copeptin predicted recurrent vascular events and death, particularly after cardioembolic TIA/stroke. Further validation is required, in particular, in studies using more extensive cardiac evaluation., (© 2015 American Heart Association, Inc.)

Background: A third of transient ischaemic attacks (TIAs) and ischaemic strokes are of undetermined cause (ie, cryptogenic), potentially undermining secondary prevention. If these events are due to occult atheroma, the risk-factor profile and coronary prognosis should resemble that of overt large artery events. If they have a cardioembolic cause, the risk of future cardioembolic events should be increased. We aimed to assess the burden, outcome, risk factors, and long-term prognosis of cryptogenic TIA and stroke., Methods: In a population-based study in Oxfordshire, UK, among patients with a first TIA or ischaemic stroke from April 1, 2002, to March 31, 2014, we compared cryptogenic events versus other causative subtypes according to the TOAST classification. We compared markers of atherosclerosis (ie, risk factors, coronary and peripheral arterial disease, asymptomatic carotid stenosis, and 10-year risk of acute coronary events) and of cardioembolism (ie, risk of cardioembolic stroke, systemic emboli, and new atrial fibrillation [AF] during follow-up, and minor-risk echocardiographic abnormalities and subclinical paroxysmal AF at baseline in patients with index events between 2010 and 2014)., Findings: Among 2555 patients, 812 (32%) had cryptogenic events (incidence of cryptogenic stroke 0·36 per 1000 population per year, 95% CI 0·23-0·49). Death or dependency at 6 months was similar after cryptogenic stroke compared with non-cardioembolic stroke (23% vs 27% for large artery and small vessel subtypes combined; p=0·26) as was the 10-year risk of recurrence (32% vs 27%; p=0·91). However, the cryptogenic group had fewer atherosclerotic risk factors than the large artery disease (p<0·0001), small vessel disease (p=0·001), and cardioembolic (p=0·008) groups. Compared with patients with large artery events, those with cryptogenic events had less hypertension (adjusted odds ratio [OR] 0·41, 95% CI 0·30-0·56; p<0·0001), diabetes (0·62, 0·43-0·90; p=0·01), peripheral vascular disease (0·27, 0·17-0·45; p<0·0001), hypercholesterolaemia (0·53, 0·40-0·70; p<0·0001), and history of smoking (0·68, 0·51-0·92; p=0·01), and compared with small vessel and cardioembolic subtypes, they had no excess risk of asymptomatic carotid disease (adjusted OR 0·64, 95% CI 0·37-1·11; p=0·11) or acute coronary events (adjusted hazard ratio [HR] 0·76, 95% CI 0·49-1·18; p=0·22) during follow-up. Compared with large artery and small vessel subtypes combined, patients with cryptogenic events also had no excess of minor-risk echocardiographic abnormalities (cryptogenic 37% vs 45%; p=0·18) or paroxysmal AF (6% vs 10%; p=0·17) at baseline or of new AF (adjusted HR 1·23, 0·78-1·95; p=0·37) or presumed cardioembolic events (1·16, 0·62-2·17; p=0·64) during follow-up., Interpretation: The clinical burden of cryptogenic TIA and stroke is substantial. Although stroke recurrence rates are comparable with other subtypes, cryptogenic events have the fewest atherosclerotic markers and no excess of cardioembolic markers., Funding: Wellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute for Health Research, Medical Research Council, and the NIHR Oxford Biomedical Research Centre., (Copyright © 2015 Li et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Many previous studies on dementia in stroke have restrictive inclusion criteria, which may result in underestimation of dementia rates. We undertook a large prospective population-based study of all transient ischemic attack and stroke to determine the impact of study entry criteria on measured rates of pre- and postevent dementia., Methods: All patients with acute transient ischemic attack or stroke from a defined population of 92 728 are referred from primary care or at hospital admission to the Oxford Vascular Study (2002-2007) and have baseline clinical and cognitive assessment and follow-up. We examined the impact of early death, other nonavailability, and commonly used selection criteria, on measured rates of dementia., Results: Among 1236 patients (mean age/SD 75.2/12.1 years, 582 men, 403 transient ischemic attack), 139 died or were otherwise unavailable for baseline assessment, 319 had prior dependency, 425 had comorbidity, 512 were aged ≥80 years, 85 were dysphasic, and 502 were hospitalized. Pre-event dementia was 3-fold higher in patients dying preascertainment (10/47, 21%) and twice as high in other nonassessed (14/92, 15%) versus assessed patients (69/1097, 6%; P=0.0006 and P=0.002) and was several-fold higher in those with prior functional impairment (24% versus 3%; P<0.0001), age >80 years (13% versus 3%; P<0.0001), dysphasia (11% versus 7%; P<0.0001), and comorbidity (10% versus 6%; P=0.04). Findings for postevent dementia were similar: prior functional impairment (40% versus 13%; P<0.0001), age >80 years (28% versus 10%; P<0.0001), dysphasia (39% versus 15%; P<0.0001), and comorbidity (20% versus 15%; P=0.04)., Conclusions: Exclusion of patients unavailable for assessment, and other widely used selection criteria, results in underestimation of the measured rate of dementia associated with transient ischemic attack and stroke., (© 2015 American Heart Association, Inc.)

Background and Purpose: Premature death after transient ischemic attack or stroke is more often because of heart disease or cancer than stroke. Previous studies found blood biomarkers not usefully predictive of nonfatal stroke but possibly of all-cause death. This association might be explained by potentially treatable occult cardiac disease or cancer. We therefore aimed to validate the association of a panel of biomarkers with all-cause death, particularly cardiac death and cancer death, despite the absence of associations with risk of nonfatal vascular events., Methods: Fifteen biomarkers were measured in 929 consecutive patients in a population-based study (Oxford Vascular Study), recruited from 2002 and followed up to 2013. Associations were determined by Cox regression. Model discrimination was assessed by c-statistic and the integrated discrimination improvement., Results: During 5560 patient-years of follow-up, none of the biomarkers predicted risk of nonfatal vascular events. However, soluble tumor necrosis factor α receptor-1, von Willebrand factor, heart-type fatty-acid-binding protein, and N-terminal pro-B-type natriuretic peptide were independently predictive of all-cause death (n=361; adjusted hazard ratio per SD, 95% confidence interval: heart-type fatty-acid-binding protein: 1.31, 1.12-1.56, P=0.002; N-terminal pro-B-type natriuretic peptide: 1.34, 1.11-1.62, P=0.002; soluble tumor necrosis factor α receptor-1: 1.45, 1.26-1.66, P=0.02; von Willebrand factor: 1.19, 1.04-1.36, P=0.01). The independent contribution of the four biomarkers taken together added prognostic information and improved model discrimination (integrated discrimination improvement=0.028, P=0.0001). N-terminal pro-B-type natriuretic peptide was most predictive of vascular death (adjusted hazard ratio=1.80, 95% confidence interval, 1.34-2.41, P<0.0001), whereas heart-type fatty-acid-binding protein predicted cancer deaths (1.64, 1.26-2.12, P=0.0002). Associations were strongest in patients without known prior cardiac disease or cancer., Conclusions: Several biomarkers predicted death of any cause after transient ischemic attack and minor stroke. N-terminal pro-B-type natriuretic peptide and heart-type fatty-acid-binding protein might improve patient selection for additional screening for occult cardiac disease or cancer, respectively. However, our results require validation in future studies., (© 2015 American Heart Association, Inc.)

Background and Purpose: Lack of reduced cognitive impairment with blood pressure (BP) lowering in trials may reflect use of the Mini-Mental State Examination (MMSE), which is insensitive to mild cognitive impairment after cerebrovascular events compared with the Montreal Cognitive Assessment. We determined relationships between impairment on MMSE versus Montreal Cognitive Assessment (MoCA) with the major physiological determinant of vascular cognitive impairment: hypertension and hypertensive arteriopathy., Methods: Cognitive impairment in consecutive patients 6 months after transient ischemic attack or minor stroke was defined as significant, mild, or none (MMSE<23, 23-26, ≥27; MoCA<20, 20-24, ≥25) and related to 20 premorbid systolic BP readings, home BP measurement (3 measurements, 3×daily for 1 month), and hypertensive arteriopathy (creatinine, stroke versus transient ischemic attack, leukoaraiosis) by ordinal regression., Results: Of 463 patients, 45% versus 28% had at least mild cognitive impairment on the MoCA versus MMSE (P<0.001). Hypertensive arteriopathy was more strongly associated with cognitive impairment on the MoCA than MMSE (creatinine: odds ratio=3.99; 95% confidence interval, 2.06-7.73 versus 2.16, 1.08-4.33; event: 1.53, 1.06-2.19 versus 1.23, 0.81-1.85; leukoaraiosis: 2.09, 1.42-3.06 versus 1.34, 0.87-2.07). Premorbid and home BP measurement systolic BP were more strongly associated with impairment on vascular subdomains of the MoCA than MMSE (odds ratio/10 mm Hg: visuospatial 1.29 versus 1.05; attention 1.18 versus 1.07; language 1.22 versus 0.91; naming 1.07 versus 0.86)., Conclusions: The stronger relationship between impairment on the MoCA with hypertensive arteriopathy, independent of age, indicates a greater sensitivity for vascular-origin cognitive impairment. Use of MoCA should improve sensitivity for cognitive impairment and treatment effects in future studies., (© 2014 American Heart Association, Inc.)

Objective: Acute coronary syndrome (ACS) is associated with increased risk of cognitive decline when compared with controls, but case:control studies are subject to selection bias. We therefore compared cognitive outcomes in ACS with transient ischaemic attack (TIA) and minor stroke, diseases with similar risk factor burden generally considered to be at high risk of cognitive decline., Design: Prospective population based cohort study, Setting: Oxford Vascular Study (OXVASC) carried out within a defined population of 91 000 in Oxfordshire, UK., Patients: 614 in total: 216 ACS, 182 TIA, 216 minor (non-disabling) stroke., Outcome Measures: Mini-Mental-State-Examination (MMSE), Telephone Interview for Cognitive Status-modified (TICSm), and Montreal Cognitive Assessment (MoCA) at 1 and 5 years., Results: Overall risk factor burden was similar across groups but ACS patients had more smoking (27% vs 14%, p<0.001) and less hypertension (45% vs 53%, p<0.01) and atrial fibrillation (6% vs 14%, p<0.001). Cognitive outcomes were worse at 1 year in ACS versus TIA patients: mean±SD MMSE 26.6±2.7 vs 27.6±2.5, p<0.0001; OR=2.14, 95% CI 1.11 to 4.13 for moderate/severe cognitive impairment (MMSE <24) with a similar trend at 5 years, and ACS outcomes were more similar to minor stroke. Memory and language versus frontal/executive subtests were relatively more impaired in ACS than TIA and minor stroke patients., Conclusions: Risk of cognitive impairment after ACS is similar to minor stroke and higher than TIA with implications for clinical practice including consent and adherence with medication. Differences in cognitive domain performance suggest a greater role for degenerative brain pathology in ACS which may be linked to vascular risk profile and cardiac factors.

Background and Purpose: Reliable comparisons of stroke incidence are important. To determine the impact of systematic assessment of patients referred with transient ischemic attack on the measured incidence and severity of stroke, we compared 2 population-based studies., Methods: Patients with first-ever stroke ascertained during 2006 through 2010 from the Dijon Stroke Registry and the Oxford Vascular (OXVASC) Study were studied. Both studies comply with the criteria for ideal incidence studies, but the OXVASC Study also systematically assessed all patients referred with transient ischemic attack. Stroke severity was measured by the National Institutes of Health Stroke Scale., Results: Among 902 incident strokes in Dijon and 748 cases in the OXVASC Study, age and gender distribution were comparable, but severity was lower in the OXVASC Study (median National Institutes of Health Stroke Scale, 2 versus 6; P<0.001). Although overall incidence of ischemic stroke was higher in the OXVASC Study (157 versus 98 of 100 000/y; incidence rate ratio, 1.59; 95% confidence interval, 1.24-2.05; P<0.001), this was accounted for by a 3-fold excess incidence of stroke with National Institutes of Health Stroke Scale ≤2 in the OXVASC Study (90 versus 29/100 000/y; P<0.001), with no difference in incidence of more severe ischemic stroke (incidence rate ratio, 0.95; 95% confidence interval, 0.68-1.33). Of all 660 incident ischemic strokes in the OXVASC Study, 375 (56.8%) cases had an National Institutes of Health Stroke Scale ≤2, of which 232 had been ascertained in the transient ischemic attack clinic. Of these 232 minor strokes, only 71 cases had a diagnosis of definite stroke documented in the medical records by the referring physician., Conclusions: Reliance on routine clinical coding underestimates the incidence of minor stroke. To improve comparability of incidence studies, researchers should assess patients referred with transient ischemic attack, and all studies should stratify incidence rates by stroke severity.

Background and Purpose: Face-to-face cognitive testing is not always possible in large studies. Therefore, we assessed the telephone Montreal Cognitive Assessment (T-MoCA: MoCA items not requiring pencil and paper or visual stimulus) and the modified Telephone Interview of Cognitive Status (TICSm) against face-to-face cognitive tests in patients with transient ischemic attack (TIA) or stroke., Methods: In a population-based study, consecutive community-dwelling patients underwent the MoCA and neuropsychological battery >1 year after TIA or stroke, followed by T-MoCA (22 points) and TICSm (39 points) at least 1 month later. Mild cognitive impairment (MCI) was diagnosed using modified Petersen criteria and the area under the receiver-operating characteristic curve (AUC) determined for T-MoCA and TICSm., Results: Ninety-one nondemented subjects completed neuropsychological testing (mean±SD age, 72.9±11.6 years; 54 males; stroke 49%) and 73 had telephone follow-up. MoCA subtest scores for repetition, abstraction, and verbal fluency were significantly worse (P<0.02) by telephone than during face-to-face testing. Reliability of diagnosis for MCI (AUC) were T-MoCA of 0.75 (95% confidence interval [CI], 0.63-0.87) and TICSm of 0.79 (95% CI, 0.68-0.90) vs face-to-face MoCA of 0.85 (95% CI, 0.76-0.94). Optimal cutoffs were 18 to 19 for T-MoCA and 24 to 25 for TICSm. Reliability of diagnosis for MCI (AUC) was greater when only multi-domain impairment was considered (T-MoCA=0.85; 95% CI, 0.75-0.96 and TICSm=0.83, 95% CI, 0.70-0.96) vs face-to-face MoCA=0.87; 95% CI, 0.76-0.97)., Conclusions: Both T-MoCA and TICSm are feasible and valid telephone tests of cognition after TIA and stroke but perform better in detecting multi-domain vs single-domain impairment. However, T-MoCA is limited in its ability to assess visuoexecutive and complex language tasks compared with face-to-face MoCA.

Background: Mild cognitive impairment (MCI) is at least as prevalent as dementia after transient ischaemic attack (TIA)/stroke and is increasingly recognised as an important outcome in observational studies and randomised trials. However, there is no consensus on how impairment should be defined, and numerous different criteria exist. Previous studies have shown that different criteria for cognitive impairment impact on prevalence rates in epidemiological studies. However, there are few data on how operational differences within established criteria (e.g. Petersen-MCI) affect measured impairment rates and the performance of short cognitive tests such as the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), particularly in cerebrovascular disease. We therefore evaluated the effect of different operational definitions on measured rates of Petersen-MCI and on reliability of short cognitive tests in patients with TIA and stroke., Methods: Consecutive patients underwent the MMSE, MoCA and neuropsychological battery ≥1 year after TIA or stroke in a population-based study. MCI was defined using the Petersen method and subclassified as single or multiple domain, both with (original) and without (modified) subjective memory impairment. Different cut-offs (>1, >1.5 and >2 standard deviations, SD) on a given test relative to published norms were compared together with use of single versus multiple tests to define domain impairment., Results: 91 non-demented subjects completed neuropsychological testing (mean age ± SD 69.7 ± 11.6 years, 54 male, 49 stroke) at a mean of 3.1 ± 1.9 years after the index event. Rates of cognitive impairment ranged from 14/91 (15%) for MCI-original at >2 SD cut-off to 61/91 (67%) MCI-modified at >1 SD cut-off, and the proportion of MCI that was multiple domain varied, e.g. 24/46 (52%) versus only 5/27 (20%) at 1 versus 2 SD cut-off for MCI-modified. Requirement for subjective memory complaint approximately halved estimates [e.g. 17 (19%) vs. 39 (43%) for MCI at 1.5 SD cut-off, single test definition], whereas use of multiple tests versus a single test to define a cognitive domain had less impact. In general, diagnostic accuracy was higher, and optimal cut-offs lower, on MMSE and MoCA for multiple-domain versus single-domain MCI, but the MoCA appeared superior for detecting MCI-modified, whereas the MMSE performed well in detecting MCI-original., Conclusion: Even within established criteria for MCI, differences in operational methodology result in 4-fold variation in MCI estimates. Optimal MMSE and MoCA cut-offs are lower, and reliability more similar, when criteria for MCI are more stringent. Our findings have implications for sample size and adjusted relative risk calculations in randomised trials and for comparisons between studies.

Background and Purpose: The Montreal Cognitive Assessment (MoCA) and Addenbrooke's Cognitive Examination-Revised (ACE-R) are proposed as short cognitive tests for use after stroke, but there are few published validations against a neuropsychological battery. We studied the relationship between MoCA, ACE-R, Mini-Mental State Examination (MMSE) and mild cognitive impairment (MCI) in patients with cerebrovascular disease and mild cognitive impairment (MCI)., Methods: One hundred consecutive non-institutionalized patients had the MMSE, MoCA, ACE-R, and National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards Neuropsychological Battery ≥ 1 year after transient ischemic attack or stroke in a population-based study. MCI was diagnosed using modified Petersen criteria in which subjective cognitive complaint is not required (equivalent to cognitive impairment-no dementia) and subtyped by number and type of cognitive domains affected., Results: Among 91 nondemented subjects completing neuropsychological testing (mean/SD age, 73.4/11.6 years; 44% female; 56% stroke), 39 (42%) had MCI (amnestic multiple domain=10, nonamnestic multiple domain=9, nonamnestic single domain=19, amnestic single domain=1). Sensitivity and specificity for MCI were optimal with MoCA <25 (sensitivity=77%, specificity=83%) and ACE-R <94 (sensitivity=83%, specificity=73%). Both tests detected amnestic MCI better than nonamnestic single-domain impairment. MMSE only achieved sensitivity >70% at a cutoff of <29, mainly due to relative insensitivity to single-domain impairment., Conclusions: The MoCA and ACE-R had good sensitivity and specificity for MCI defined using the Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Battery ≥1 year after transient ischemic attack and stroke, whereas the MMSE showed a ceiling effect. However, optimal cutoffs will depend on use for screening (high sensitivity) or diagnosis (high specificity). Lack of timed measures of processing speed may explain the relative insensitivity of the MoCA and ACE-R to single nonmemory domain impairment.

Background and Purpose: Acute cognitive impairment and delirium occur after major stroke and are associated with poor cognitive outcome. We conducted a population-based study to determine whether transient cognitive impairment (TCI) is seen acutely after cerebral transient ischemic attack (TIA) or minor stroke, and whether it predicts long-term cognitive decline., Methods: Mini-mental-state examination was performed in consecutive testable patients with TIA or minor stroke (National Institutes of Health Stroke Scale ≤3) seen acutely (1-7 days) in the Oxford Vascular Study (2002-2005) versus after 7 days, and in referrals seen acutely who had a subsequent noncerebrovascular diagnosis. We defined TCI as a baseline Mini-mental-state examination score ≥2 points below the 1-month follow-up score, and identified cognitive impairment (Montreal Cognitive Assessment [MoCA] <26/30) and severe dementia at 1-, 2-, and 5-year follow-up., Results: In 280 TIA and minor stroke patients (mean age/SD 73.5/11.8 years), TCI was more frequent in those seen at 1 to 7 days (80/206; 38.9%) versus later (14/74; 19%; P=0.002) or in noncerebrovascular patients (10/47; 21%; P=0.004). TCI was associated with acute confusion (OR, 5.5; 95% CI, 2.5-11.7; P<0.0001), acute infarct on computed tomography (OR, 2.0; 1.2-3.5; P=0.01), and with residual focal deficits (OR,1.94; 1.13-3.34; P=0.01). However, it was still seen acutely in those whose focal deficits had resolved by time of assessment (41/120; 34%). Although patients with TCI had similar Mini-mental-state examination score by 1 month compared with those without TCI, their 5-year risks of cognitive impairment (OR, 4.3; 1.2-15.7; P=0.03) and severe dementia (OR, 4.9; 1.0-25.8; P=0.05) were increased., Conclusions: TCI is a manifestation of TIA and minor stroke, and may persist beyond resolution of focal symptoms. Our findings have implications for definitions in TIA and minor stroke and suggest that cognitive fragility may be revealed by minor cerebrovascular events.

Background: The risk of recurrent stroke is up to 10% in the week after a transient ischaemic attack (TIA) or minor stroke. Modelling studies suggest that urgent use of existing preventive treatments could reduce the risk by 80-90%, but in the absence of evidence many health-care systems make little provision. Our aim was to determine the effect of more rapid treatment after TIA and minor stroke in patients who are not admitted direct to hospital., Methods: We did a prospective before (phase 1: April 1, 2002, to Sept 30, 2004) versus after (phase 2: Oct 1, 2004, to March 31, 2007) study of the effect on process of care and outcome of more urgent assessment and immediate treatment in clinic, rather than subsequent initiation in primary care, in all patients with TIA or minor stroke not admitted direct to hospital. The study was nested within a rigorous population-based incidence study of all TIA and stroke (Oxford Vascular Study; OXVASC), such that case ascertainment, investigation, and follow-up were complete and identical in both periods. The primary outcome was the risk of stroke within 90 days of first seeking medical attention, with independent blinded (to study period) audit of all events., Findings: Of the 1278 patients in OXVASC who presented with TIA or stroke (634 in phase 1 and 644 in phase 2), 607 were referred or presented direct to hospital, 620 were referred for outpatient assessment, and 51 were not referred to secondary care. 95% (n=591) of all outpatient referrals were to the study clinic. Baseline characteristics and delays in seeking medical attention were similar in both periods, but median delay to assessment in the study clinic fell from 3 (IQR 2-5) days in phase 1 to less than 1 (0-3) day in phase 2 (p<0.0001), and median delay to first prescription of treatment fell from 20 (8-53) days to 1 (0-3) day (p<0.0001). The 90-day risk of recurrent stroke in the patients referred to the study clinic was 10.3% (32/310 patients) in phase 1 and 2.1% (6/281 patients) in phase 2 (adjusted hazard ratio 0.20, 95% CI 0.08-0.49; p=0.0001); there was no significant change in risk in patients treated elsewhere. The reduction in risk was independent of age and sex, and early treatment did not increase the risk of intracerebral haemorrhage or other bleeding., Interpretation: Early initiation of existing treatments after TIA or minor stroke was associated with an 80% reduction in the risk of early recurrent stroke. Further follow-up is required to determine long-term outcome, but these results have immediate implications for service provision and public education about TIA and minor stroke.