Sarah T. Pendlebury

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 (r2=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 ≥27, whereas only 5 patients had MoCA ≥26 and MMSE <27 (P<0.0001). In patients with MMSE ≥27, MoCA <26 was associated with higher Rankin scores (P=0.0003) and deficits in delayed recall, abstraction, visuospatial/executive function, and sustained attention. Conclusion— 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.

The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis.

Although multiple sclerosis (MS) is an inflammatory demyelinating disease, there can be substantial axonal injury and loss. We therefore hypothesized that adaptive cortical changes may contribute to limiting functional impairment, particularly in the early stages of the disease. To test our hypothesis, we used functional magnetic resonance imaging (MRI) to characterize the localization and volumes of activation in the motor cortex during simple flexion‐extension finger movements. There were differences in the patterns of cortical activation with movement between the 12 MS patients and the 12 normal controls. All patients showed greater relative supplementary motor area activation than did the normal controls. The relative hemispheric lateralization of sensorimotor cortex (SMC) activation decreased in direct proportion to the total cerebral T2‐weighted MRI hyperintense lesion load. This appeared to be due primarily to increases in ipsilateral SMC activation with increasing lesion load in white matter of the hemisphere contralateral to the limb moved. The center of activation in the contralateral SMC was shifted a mean of 8.8 mm posterior in patients relative to controls, providing additional evidence for cortical adaptive responses to injury. The magnitude of this posterior shift in the SMC activation increased with greater T2 lesion loads. These observations demonstrate that cortical recruitment for simple finger movements can change both quantitatively and qualitatively in the SMCs of MS patients, suggesting that cortical reorganization or “unmasking” of latent pathways can contribute to functional recovery. These adaptive changes are another factor potentially limiting the strength of the relationship between MRI measures of pathology and clinical measures of disability. Ann Neurol 2000;47:606–613

Functional MRI detects posterior shifts in primary sensorimotor cortex activation after stroke: evidence of local adaptive reorganization?

Background and Purpose Further recovery from stroke can occur late, long after the end of the apparent evolution of pathological changes. This observation and evidence obtained from functional imaging for altered patterns of activation after brain injury suggest that cortical reorganization may contribute to recovery. Here, we have tested for potentially adaptive reorganization in the primary sensorimotor cortex. Methods We used functional MRI to study brain activation with dominant hand movement in right-handed healthy control subjects (n=20) and in patients after subcortical ischemic infarcts causing mild to moderate right hemiparesis (n=8). The numbers of pixels activated above threshold and the geometric centers of activation clusters were determined. Results Although random-effects analysis identified some differences in activation maxima, similar regions of the brain were activated with sequential finger tapping in the patient and control groups. However, consistent with the heterogeneity in the locations, sizes, and times after the infarcts, patterns and magnitudes of activation showed some heterogeneity between patients. Nonetheless, for the group as a whole, there was a decreased motor cortex lateralization index (−0.1±0.7 in patients and 0.7±0.3 in control subjects, P =0.05). The geometric center of activation of the primary sensorimotor cortex activation cluster contralateral to the affected hand in patients was also shifted posteriorly (mean 12 mm, P <0.04) relative to that of the control subjects. To confirm the latter observation, the activation response with a simple hand-tapping task was examined in some of the subjects. With this task, there was also a trend (mean 10 mm, P =0.07) toward a more posterior activation in patients. Conclusions These results confirm altered patterns of activation in the contralateral and ipsilateral primary sensorimotor cortices after recovery from strokes causing hemiparesis. These (and other changes) suggest that modulation of widely distributed parts of the cortical network for motor control may contribute to adaptations leading to functional recovery after stroke.

MoCA, ACE-R, and MMSE Versus the National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards Neuropsychological Battery After TIA and Stroke

Background and Purpose— The Montreal Cognitive Assessment (MoCA) and Addenbrookes 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.

Critical Appraisal of the Design and Reporting of Studies of Imaging and Measurement of Carotid Stenosis

BACKGROUND AND PURPOSE Several hundred studies have been published over the last few years on imaging and measurement of carotid stenosis. Despite all this research, there is still no consensus about how best to image and measure stenosis. One possible explanation for this is that many of the studies have not been large enough or methodologically sound enough to allow useful conclusions to be drawn. We aimed to assess the design and methods of a random sample of published studies of imaging and measurement of carotid stenosis using 9 simple criteria. METHODS A formal literature search was performed for studies of imaging and measurement of carotid stenosis. Two subsets were randomly selected for detailed assessment: 20 studies published before 1991 and 20 published between 1993 and 1997 (some years after the initial publication of the ECST and NASCET trials). The criteria used to assess the selected studies were as follows: prospective rather than retrospective study design; patient selection based on a consecutive series or a random sample; adequate detail of study population; adequate detail of imaging techniques; inclusion of all investigations, ie, patients with poor-quality imaging were not excluded; blinded assessment of images; adequate detail of derivation of measurement of stenosis from images or data; adequate data on the reproducibility of measurements of stenosis; and study powered according to a sample-size calculation. RESULTS There were many basic methodological deficiencies in both subsets of studies, with relatively little evidence of improvement with time. For example, only 33% of studies were prospective, only 45% studied a consecutive or random selection of patients, and only 38% reported any data on the reproducibility of measurements. More than half of the studies satisfied < or =4 of the 9 quality criteria. However, there was considerable variation between studies, with 7 studies satisfying > or = 7 criteria and 10 studies satisfying < or =2. No study was based on a sample-size calculation. The number of patients studied was often small, particularly in the more recent studies: median sample size was 100 in the 1970-1990 studies and 58 in the 1993-1997 studies (P<0.0001). CONCLUSIONS The design and reporting of published studies of imaging and measurement of carotid stenosis are poor and have not improved much in recent years. The majority of published studies are not of a sufficient standard to enable the results to be used to inform clinical practice. The utility of future studies could be improved considerably by better adherence to 9 simple methodological guidelines.

Transient Cognitive Impairment in TIA and Minor Stroke

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.

Risk of Recurrent Stroke, Other Vascular Events and Dementia after Transient Ischaemic Attack and Stroke

The early risk of recurrence after transient ischaemic attack (TIA) or minor stroke is high, ranging from 11% at 7 days in population-based studies, where patients are seen non-urgently, to 3% at 7 days in studies where patients are seen urgently in specialist services. In long-term (up to 10 years) studies of vascular risks after TIA and stroke, the risk of stroke is highest early after the event, and then falls, whereas the risk of coronary events is constant over the follow-up period at around 2% per year. In contrast to the early risk after TIA and stroke, the long-term risks are more dependent on the underlying vascular risk factors than the characteristics of the event itself. Stroke is also associated with an increased risk of dementia. Prevalence of post-stroke dementia varies between studies but is around 28% at 3 months in hospital-based studies where pre-stroke dementia was not excluded and 18% in hospital-based studies excluding pre-stroke dementia. Risk factors for post-stroke dementia include low education, prior or recurrent stroke, and older age. In conclusion, available data suggest that the risk of recurrent vascular events is considerable after TIA and stroke, even in the longer term, and that there is also a high risk of dementia after stroke. However, more studies are required to determine medium- and long-term outcomes in the current era of aggressive secondary preventive therapy.

Axonal injury in the internal capsule correlates with motor impairment after stroke.

Background and Purpose--Magnetic resonance spectroscopy (MRS) in ischemic stroke has shown a correlation between N-acetylaspartate (NAA) loss from the infarcted region and disability. We tested the hypothesis that NAA loss in the descending motor pathways, measured at the level of the posterior limb of the internal capsule, would determine motor deficit after a cortical, subcortical, or striatocapsular stroke. Methods--Eighteen patients with first ischemic stroke causing a motor deficit were examined between 1 month and 5 years after stroke. T2-weighted imaging of the brain and localized proton (voxel, 1.5x2x2 cm3) MRS from the posterior limb of each internal capsule were performed and correlated to a motor deficit score. Results--Mean internal capsule NAA was significantly lower in the patient group as a whole compared with the control group (P<0.001). Reductions in internal capsule NAA on the side of the lesion were seen in cases of cortical stroke in which there was no extension of the stroke into the voxel as well as in cases of striatocapsular stroke involving the voxel region. There was a strong relationship between reduction in capsule NAA and contralateral motor deficit (log curve, r2=0.9, P<0.001). Conclusions--Axonal injury in the descending motor pathways at the level of the internal capsule correlated with motor deficit in patients after stroke. This was the case for strokes directly involving the internal capsule and for strokes in the motor cortex and subcortex in which there was presumed anterograde axonal injury.

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

Test accuracy of cognitive screening tests for diagnosis of dementia and multidomain cognitive impairment in stroke.

99 831 (SD, 67 020) for TIA and