Yeonwook Kang

Cognitive Impairment Evaluated With Vascular Cognitive Impairment Harmonization Standards in a Multicenter Prospective Stroke Cohort in Korea

Background and Purpose— Since the Vascular Cognitive Impairment Harmonization Standards (VCIHS) neuropsychological test protocol was proposed by the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network, no studies have applied this neuropsychological protocol to poststroke survivors in a large-scale, multicenter stroke cohort. We determined the frequency of vascular cognitive impairment (VCI) and investigated the feasibility of using the Korean version of the VCIHS neuropsychological protocol in a multicenter, hospital-based stroke cohort in Korea. Methods— We prospectively enrolled 620 subjects with ischemic stroke within 7 days of symptom onset among 899 patients who were consecutively admitted to 12 university hospitals in Korea. Neuropsychological assessments using the 60-minute Korean VCIHS neuropsychological protocol were administered at 3 months after stroke. Results— Of the 620 patients, 506 were followed up at 3 months after stroke. Of these, 353 (69.8%) were evaluated for cognitive function using the 60-minute Korean VCIHS neuropsychological protocol. The frequency of VCI at 3 months was 62.6%: VCI with no dementia in 49.9% and vascular dementia in 12.7%. Old age (P=0.014), poor functional outcomes at 3 months (P=0.029), and stroke subtypes other than small vessel disease (P=0.004) were independent risk factors of VCI. Conclusions— VCI, evaluated using the Korean VCIHS neuropsychological protocol, is substantial at 3 months after ischemic stroke in Korea. The use of the 60-minute Korean VCIHS neuropsychological protocol was feasible in large-scale multicenter studies.

Hormone replacement therapy in postmenopausal women with Alzheimer’s disease: a randomized, prospective study

OBJECTIVE To compare the therapeutic efficacy of hormone replacement therapy (HRT) and tacrine in Alzheimers disease. DESIGN Six-month, randomized, open-label study. SETTING University hospital. PATIENT(S) Fifty-five women with mild to moderate Alzheimers disease were randomly assigned to tacrine (n = 26) or HRT (n = 29). INTERVENTION(S) In the tacrine group, an initial dose of 40 mg/day was increased up to 160 mg/day. In the HRT group, conjugated equine estrogen was given to patients without uteri (n = 3) or together with micronized progesterone to patients with uteri (n = 26). MAIN OUTCOME MEASURE(S) Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test, Boston Naming Test, Controlled Oral Word Association Test, Geriatric Depression Scale, Hamilton Depression Scale (HDS), and Instrumental Activities of Daily Living (IADL). RESULT(S) Thirty-three patients who completed the outcome measures (tacrine, 17; HRT, 16) were included in an intent-to-treat analysis. The results did not differ between groups except for IADL, which rated more highly after HRT. Apolipoprotein E genotype effects were assessed. MMSE and HDS scores were improved after tacrine treatment in epsilon 4-negative patients. CONCLUSION(S) Overall efficacy of estrogen plus progesterone combination was similar to tacrine for cognition and mood, but greater for ADL. In epsilon 4-negative patients, tacrine is preferable for cognition and mood.

Impact of post-stroke cognitive impairment with no dementia on health-related quality of life.

Background and Purpose Health-related quality of life (HRQoL) is a multidimensional concept that signifies a subjective evaluation of perceived health; hence, it has gained wide acceptance in geriatrics. However, its application has not been tested in patients with post-stroke cognitive impairment with no dementia (PSCIND). We investigated whether PSCIND interferes with HRQoL measured by EQ-5D, compared the findings to those of healthy people with normal cognition, and evaluated the influence of each cognitive domain on this score. Methods In total, 1,528 subjects were identified who had undergone neuropsychological assessment using the 60-min protocol of the Korean version of Vascular Cognitive Impairment Harmonization Standards, EQ-5D, and magnetic resonance imaging at the stroke prevention clinic. Fifty PSCIND patients were matched to 50 post-stroke dementia (PSD) patients and 50 normal age- (±3 years) and sex-matched controls. The effects of PSCIND, PSD, and control groups upon the EQ-5Dindex score were tested by generalized estimating equation modeling. Results Estimated means±standard errors of EQ-5Dindex scores were as follows: 0.94±0.06 (control group), 0.86±0.08 (PSCIND group), and 0.61±0.32 (PSD group); and the difference among the three groups was statistically significant (P<0.0001). Pairwise comparisons showed that EQ-5Dindex scores in the PSCIND group differed from those in the PSD and control groups (both P<0.01). No cognitive domain was specifically associated with EQ-5Dindex scores after adjusting for functional status. Conclusions This study shows that PSCIND may interfere with the quality of life in stroke victims.

Trail Making Test Elucidates Neural Substrates of Specific Poststroke Executive Dysfunctions

Background and Purpose— Poststroke cognitive impairment is typified by prominent deficits in processing speed and executive function. However, the underlying neuroanatomical substrates of executive deficits are not well understood, and further elucidation is needed. There may be utility in fractionating executive functions to delineate neural substrates. Methods— One test amenable to fine delineation is the Trail Making Test (TMT), which emphasizes processing speed (TMT-A) and set shifting (TMT-B-A difference, proportion, quotient scores, and TMT-B set-shifting errors). The TMT was administered to 2 overt ischemic stroke cohorts from a multinational study: (1) a chronic stroke cohort (N=61) and (2) an acute–subacute stroke cohort (N=45). Volumetric quantification of ischemic stroke and white matter hyperintensities was done on magnetic resonance imaging, along with ratings of involvement of cholinergic projections, using the previously published cholinergic hyperintensities projections scale. Damage to the superior longitudinal fasciculus, which colocalizes with some cholinergic projections, was also documented. Results— Multiple linear regression analyses were completed. Although larger infarcts (&bgr;=0.37, P<0.0001) were associated with slower processing speed, cholinergic hyperintensities projections scale severity (&bgr;=0.39, P<0.0001) was associated with all metrics of set shifting. Left superior longitudinal fasciculus damage, however, was only associated with the difference score (&bgr;=0.17, P=0.03). These findings were replicated in both cohorts. Patients with ≥2 TMT-B set-shifting errors also had greater cholinergic hyperintensities projections scale severity. Conclusions— In this multinational stroke cohort study, damage to lateral cholinergic pathways and the superior longitudinal fasciculus emerged as significant neuroanatomical correlates for executive deficits in set shifting.

Cortical Hubs and Subcortical Cholinergic Pathways as Neural Substrates of Poststroke Dementia

Background and Purpose— A role of neural networks in the development of poststroke dementia has not been clearly established. We hypothesized that stroke-mediated disruption of subcortical cholinergic pathway or large-scale neural networks contributes to poststroke dementia. Methods— A matched case–control study was conducted in a predetermined cohort with acute ischemic stroke. Cases were defined as newly developed dementia diagnosed >3 months after stroke using the Korean Vascular Cognitive Impairment Harmonization Standards. Each case was matched to 2 controls for age, education, and initial stroke severity. The Cholinergic Pathways HyperIntensities Scale was applied with some modifications to characterize disruption of cholinergic pathways by acute stroke lesions. Involvement of major cortical hub locations of the default mode network, central executive network, and salience network was also investigated. Results— After matching, 38 cases and 66 matched controls were included. Cholinergic Pathways HyperIntensities Scale scores were significantly higher in cases than in controls (2.2±2.9 versus 0.9±1.4). Acute ischemic lesions affecting the default mode and central executive networks were more frequently observed in cases compared with controls (36.8% versus 7.6% and 26.3% versus 6.1%, respectively). These findings remained significant in the multiple logistic regression models adjusted for various sets of potential confounders. Lesion location analysis revealed that cases were more likely to have acute lesions in the left corona radiata, hippocampal formation, and posterior parietal cortex. Conclusions— Disruption of cholinergic pathways and major hubs of large-scale neural networks might contribute to newly developed dementia after acute ischemic stroke.

Line quadrisection errors in normal subjects.

Many studies have investigated line bisection behaviors in normal individuals and patients with hemispatial neglect. However, little is known about what happens when subjects attempt to fractionate line into more than two equal components (e.g., line quadrisection). Thirty right handed normal subjects were asked to place a mark either 25% (left quadrisection) or 75% (right quadrisection) of the distance along on a 240 mm line. On average, they placed the left quadrisection mark significantly to the left (- 4.2+/-6.7 mm) from the true quadrisection point but they were relatively accurate on the right quadrisection task (1.0+/-6.7 mm). However, comparison of actual quadrisection performances with those of expected performance based on subjective midpoint disclosed that both right and left quadrisection marks deviate toward each end of the line. Individual data analysis also support this trend because majority of subjects showed the lateral deviation in either or both quadrisection tasks. Therefore, in the left quadrisection task the pseudoneglect (leftward bias) in bisection and the lateral bias are additive, resulting in a robust left lateral deviation, whereas in the right quadrisection, these two biases nullify each other, resulting in accurate performance.

Post-stroke memory impairment among patients with vascular mild cognitive impairment

BackgroundThe American Stroke Association/American Heart Association recommended the criteria for diagnosis of vascular cognitive impairment and memory impairment (MI) is a feature in the classification of vascular mild cognitive impairment (VaMCI). VaMCI patients with MI may differ in terms of infarct location or demographic features, so we evaluated the clinical characteristics associated with MI in patients with VaMCI.MethodsA prospective multicenter study enrolled 353 acute ischemic stroke patients who underwent evaluation using the Korean Vascular Cognitive Impairment Harmonization Standard Neuropsychological Protocol at three months after onset. The association between MI and demographic features, stroke risk factors, and infarct location was assessed.ResultsVaMCI was diagnosed in 141 patients, and 58 (41.1%) exhibited MI. Proportions of men and of left side infarcts were higher in VaMCI with MI than those without (75.9 vs. 57.8%, P = 0.03, 66.7 vs. 47%, P = 0.02). Multiple logistic analyses revealed that male sex (odds ratio [OR] 3.07, 95% confidence interval [95% CI] 1.12-8.42), left-side infarcts (OR 3.14, 95% CI 1.37-7.20), and basal ganglia/internal capsule infarcts (OR 4.53, 95% CI 1.55-13.22) were associated with MI after adjusting other demographic variables, vascular risk factors, and subtypes of stroke.ConclusionsMI is associated with sex and infarct location in VaMCI patients.

Highly variable blood pressure as a predictor of poor cognitive outcome in patients with acute lacunar infarction.

Objective and Background:Many patients develop cognitive impairment after an acute stroke. It is not clear whether blood pressure variability is a prognostic factor for cognitive impairment. We aimed to determine the association between blood pressure variability on hospital admission and cognitive outcome in patients with acute lacunar infarction. Methods:We performed a retrospective analysis on 22 men and 14 women (mean age, 61.8 years) who had completed a cognitive evaluation 3 months after onset of an acute lacunar infarction. The patients had no previous functional disability or dementia, stenosis in major cerebral arteries, cardiac embolic sources, or infarct in strategic territories for cognition. We used standard deviation and coefficient of variance as parameters of blood pressure variability, and each cognitive function test z score as an outcome parameter. We performed linear regression analysis to assess the relationship between blood pressure variability and cognition, adjusted for vascular risk factors, severity of neurologic deficits, and mean blood pressure. Results:High variability of both systolic and diastolic blood pressure was significantly associated with low z scores on the Controlled Oral Word Association Test and the Digit Symbol Coding test (P<0.01). High variability of diastolic blood pressure was significantly associated with low z scores on the Korean Mini-Mental State Examination and Seoul Verbal Learning Test delayed recall (P<0.01). Conclusions:Highly variable blood pressure on admission for acute lacunar infarction may predict poor cognitive outcomes, especially frontal lobe dysfunction.

Medial Temporal Atrophy and Memory Dysfunction in Poststroke Cognitive Impairment-No Dementia

Background and Purpose It was recently reported that the prevalence of poststroke memory dysfunction might be higher than previously thought. Stroke may exist concomitantly with underlying Alzheimers disease (AD), and so we determined whether post-stroke memory dysfunction indicates manifestation of underlying subclinical AD. Methods Of 1201 patients in a prospective cognitive assessment database, we enrolled subjects with poststroke amnestic vascular cognitive impairment-no dementia (aVCIND; n=48), poststroke nonamnestic vascular cognitive impairment-no dementia (naVCIND; n=50), and nonstroke amnestic mild cognitive impairment (aMCI; n=65). All subjects had cognitive deficits, but did not meet the criteria for dementia. A standardized neuropsychological test battery and magnetic resonance imaging were performed at least 90 days after the index stroke (mean, 473 days). Visual assessment of medial temporal atrophy (MTA) was used as a measure of underlying AD pathology. Results The MTA score was significantly lower in the naVCIND group (0.64±0.85, mean±SD) than in the aVCIND (1.10±1.08) and aMCI (1.45±1.13; p<0.01) groups. Multivariable ordinal logistic regression analysis revealed that compared with naVCIND, aVCIND [odds ratio (OR)=2.69; 95% confidence interval (CI)=1.21-5.99] and aMCI (OR=5.20; 95% CI=2.41-11.23) were significantly associated with increasing severity of MTA. Conclusions Our findings show that compared with poststroke naVCIND, the odds of having more-severe MTA were increased for poststroke aVCIND and nonstroke aMCI.

Prediction of post-stroke dementia using NINDS-CSN 5-minute neuropsychology protocol in acute stroke.

BACKGROUND The National Institute of Neurological Disease and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute neuropsychology protocol consists of only verbal tasks, and is proposed as a brief screening method for vascular cognitive impairment. We evaluated its feasibility within two weeks after stroke and ability to predict the development of post-stroke dementia (PSD) at 3 months after stroke. METHOD We prospectively enrolled subjects with ischemic stroke within seven days of symptom onset who were consecutively admitted to 12 university hospitals. Neuropsychological assessments using the NINDS-CSN 5-minute and 60-minute neuropsychology protocols were administered within two weeks and at 3 months after stroke onset, respectively. PSD was diagnosed with reference to the American Heart Association/American Stroke Association statement, requiring deficits in at least two cognitive domains. RESULTS Of 620 patients, 512 (82.6%) were feasible for the NINDS-CSN 5-minute protocol within two weeks after stroke. The incidence of PSD was 16.2% in 308 subjects who had completed follow-up at 3 months after stroke onset. The total score of the NINDS-CSN 5-minute protocol differed significantly between those with and without PSD (4.0 ± 2.7, 7.4 ± 2.7, respectively; p < 0.01). A cut-off value of 6/7 showed reasonable discriminative power (sensitivity 0.82, specificity 0.67, AUC 0.74). The NINDS-CSN 5-minute protocol score was a significant predictor for PSD (adjusted odds ratio 6.32, 95% CI 2.65-15.05). DISCUSSION The NINDS-CSN 5-minute protocol is feasible to evaluate cognitive functions in patients with acute ischemic stroke. It might be a useful screening method for early identification of high-risk groups for PSD.