Methodological Factors in Determining Risk of Dementia After Transient Ischemic Attack and Stroke: (II) Effect of Attrition on Follow-Up.

BACKGROUND AND PURPOSE: Cognitive outcomes in cohorts and trials are often based only on face-to-face clinic assessment. However, cognitive impairment is strongly associated with increased morbidity and mortality, leading to substantial loss to clinic follow-up. In the absence of previous population-based data, we determined the effect of such attrition on measured risk of dementia after transient ischemic attack and stroke. METHODS: Patients with transient ischemic attack or stroke prospectively recruited (2002-2007) into the Oxford Vascular (OXVASC) study had baseline clinical/cognitive assessment and follow-up to 2014. Dementia was diagnosed through face-to-face clinic interview, supplemented by home visits and telephone assessment in patients unable to attend clinic and by hand-searching of primary care records in uncontactable patients. RESULTS: Of 1236 patients (mean age/SD, 75.2/12.1 years; 582 men), 527 (43%) died by 5-year follow-up. Follow-up assessment rates (study clinic, home visit, or telephone) of survivors were 947 in 1026 (92%), 857 in 958 (89%), 792 in 915 (87%), and 567 in 673 (84%) at 1, 6, 12 months and 5 years. Dementia developed in 260 patients, of whom 110 (42%; n=50 primary care records, n=49 home visit, and n=11 telephone follow-up) had not been available for face-to-face clinic follow-up at the time of diagnosis. The 5-year cumulative incidence of postevent dementia was 29% (26%-32%) overall but was only 17% (14% to 19%) in clinic assessed versus 45% (39%-51%) in nonclinic-assessed patients (P difference<0.001). CONCLUSIONS: Exclusion of patients unavailable for clinic follow-up reduces the measured risk of postevent dementia. Use of multiple follow-up methods, including home visits, telephone assessments, and consent, to access primary care records substantially increases ascertainment of longer-term dementia outcomes.

Telephone assessment of cognition after transient ischemic attack and stroke: modified telephone interview of cognitive status and telephone Montreal Cognitive Assessment versus face-to-face Montreal Cognitive Assessment and neuropsychological battery.

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.

Population-based study of disability and institutionalization after transient ischemic attack and stroke: 10-year results of the Oxford Vascular Study.

BACKGROUND AND PURPOSE: Long-term outcome information after transient ischemic attack (TIA) and stroke is required to help plan and allocate care services. We evaluated the impact of TIA and stroke on disability and institutionalization over 5 years using data from a population-based study. METHODS: Patients from a UK population-based cohort study (Oxford Vascular Study) were recruited from 2002 to 2007 and followed up to 2012. Patients were followed up at 1, 6, 12, 24, and 60 months postevent and assessed using the modified Rankin scale. A multivariate regression analysis was performed to assess the predictors of disability postevent. RESULTS: A total of 748 index stroke and 440 TIA cases were studied. For patients with TIA, disability levels increased from 14% (63 of 440) premorbidly to 23% (60 of 256) at 5 years (P=0.002), with occurrence of subsequent stroke being a major predictor of disability. For stroke survivors, the proportion disabled (modified Rankin scale >2) increased from 21% (154 of 748) premorbidly to 43% (273 of 634) at 1 month (P<0.001), with 39% (132 of 339) of survivors disabled 5 years after stroke. Five years postevent, 70% (483 of 690) of patients with stroke and 48% (179 of 375) of patients with TIA were either dead or disabled. The 5-year risk of care home institutionalization was 11% after TIA and 19% after stroke. The average 5-year cost per institutionalized patient was $99,831 (SD, 67 020) for TIA and $125,359 (SD, 91 121) for stroke. CONCLUSIONS: Our results show that 70% of patients with stroke are either dead or disabled 5 years after the event. Thus, there remains considerable scope for improvements in acute treatment and secondary prevention to reduce postevent disability and institutionalization.

Underestimation of cognitive impairment by Mini-Mental State Examination versus the Montreal Cognitive Assessment in patients with transient ischemic attack and stroke: a population-based study.

BACKGROUND AND PURPOSE: The Mini-Mental State Examination (MMSE) is insensitive to mild cognitive impairment and executive function. The more recently developed Montreal Cognitive Assessment (MoCA), an alternative, brief 30-point global cognitive screen, might pick up more cognitive abnormalities in patients with cerebrovascular disease. METHODS: In a population-based study (Oxford Vascular Study) of transient ischemic attack and stroke, the MMSE and MoCA were administered to consecutive patients at 6-month or 5-year follow-up. Accepted cutoffs of MMSE <27 and MoCA <26 were taken to indicate cognitive impairment. RESULTS: Of 493 patients, 413 (84%) were testable. Untestable patients were older (75.5 versus 69.9 years, P<0.001) and often had dysphasia (24%) or dementia (15%). Although MMSE and MoCA scores were highly correlated (r(2)=0.80, P<0.001), MMSE scores were skewed toward higher values, whereas MoCA scores were normally distributed: median and interquartile range 28 (26 to 29) and 23 (20 to 26), respectively. Two hundred ninety-one of 413 (70%) patients had MoCA <26 of whom 162 had MMSE > or =27, whereas only 5 patients had MoCA > or =26 and MMSE <27 (P<0.0001). In patients with MMSE > or =27, MoCA <26 was associated with higher Rankin scores (P=0.0003) and deficits in delayed recall, abstraction, visuospatial/executive function, and sustained attention. CONCLUSIONS: The MoCA picked up substantially more cognitive abnormalities after transient ischemic attack and stroke than the MMSE, demonstrating deficits in executive function, attention, and delayed recall.

Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison.

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.

Lack of reproducibility of assessment of aspirin responsiveness by optical aggregometry and two platelet function tests.

The term aspirin-resistance describes the failure of aspirin to inhibit thromboxane A(2) production. Many new tests have become available for potentially measuring aspirin responses but some are non-specific and do not isolate COX-1 activity. We previously demonstrated that agreement between two tests (PFA-100 and VerifyNow-ASA) and light transmission aggregation (LTA) was no greater than would be expected by chance. In this study we re-tested the same patients using identical methods after 1 year to determine whether poor agreement might have been due to assessment in the acute phase and whether the results of the individual tests are consistent over time. Platelet function by all three tests was re-tested in the 72 patients who were alive and still receiving low dose ASA therapy one year after the first tests were performed. On re-testing the prevalence of ASA non-responsiveness compared with baseline was 10% vs 17% by the VerifyNow-ASA test, 25% vs 22% by the PFA-100(R), and 1% vs 5% by LTA. Agreement between the tests at 1 year remained poor (kappas: 0.02-0.17) and only one patient was identified as a non-responder by all three tests, in keeping with the theoretical differences between the tests. Within test comparisons of baseline vs 1 year showed moderate agreement for the PFA-100(R) (kappa = 0.44, 95% CI 0.19-0.68, p = 0.0006), a fair agreement for VerifyNow-ASA (kappa = 0.34, 0.04-0.64, p = 0.12) and poor agreement for LTA (kappa = 0.14, -0.11 -0.39, p = 0.24 for ADP; kappa = 0.09, -0.21-0.39, p = 0.41 for arachidonic acid). Agreement between the three tests in identifying aspirin non-responsiveness remained poor in patients who had been taking aspirin for at least 1 year follow-up. Reproducibility over time was no greater than chance for LTA and only moderate for VerifyNow-ASA and PFA-100(R). Lack of consistency over time in identification of apparently non-responsiveness individuals is likely to substantially undermine any ability of these tests to predict risk of recurrent vascular events.