Clinical Significance of Physical Frailty in Subjects With Subjective Cognitive Decline: A Prospective Study With Amyloid PET Data

Background@#and Purpose Physical frailty is known to be closely associated with cognitive impairment and to be an early sign of Alzheimer’s disease. We aimed to understand the characteristics of physical frailty and define factors associated with physical frailty in subjects with subjective cognitive decline (SCD) by analyzing amyloid data. @*Methods@#We prospectively enrolled subjects with SCD from a cohort study to identify predictors for the clinical progression to mild cognitive impairment or dementia from SCD (CoSCo). All of the subjects underwent brain magnetic resonance imaging, and brain amyloid positron-emission tomography (PET) to detect amyloid beta plaques. Self-reported exhaustion, handgrip strength, and gait speed were used to measure physical frailty. @*Results@#Of 120 subjects with SCD, 26 (21.7%) were amyloid-positive in PET. Female (odds ratio [OR]=3.79, p=0.002) and amyloid-PET-positive (OR=3.80, p=0.008) subjects with SCD were at high risks of self-reported exhaustion. Amyloid PET positivity (OR=3.22, p=0.047) and high burden from periventricular white-matter hyperintensity (OR=3.34, 95% confidence interval=1.18–9.46, p=0.023) were significantly associated with a weaker handgrip. The subjects with SCD with self-reported exhaustion and weaker handgrip presented with lower cognitive performance in neuropsychological tests, especially for information processing speed and executive function. Subjects with a slower gait performed worse in visual memory function tests. @*Conclusions@#Amyloid PET positivity was associated with a higher risk of self-reported exhaustion and weaker handgrip in subjects with SCD. The subjects with SCD and physical frailty also performed worse in neuropsychological tests.

Coexistence of Cerebral Microbleeds and Amyloid Pathology in Patients with Cognitive Complaints

Early Functional Connectivity Predicts Recovery from Visual Field Defects after Stroke / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: We aimed to assess whether early resting-state functional connectivity (RSFC) changes measured via functional magnetic resonance imaging (fMRI) could predict recovery from visual field defect (VFD) in acute stroke patients. METHODS: Patients with VFD due to acute ischemic stroke in the visual cortex and age-matched healthy controls were prospectively enrolled. Serial resting-state (RS)-fMRI and Humphrey visual field (VF) tests were performed within 1 week and at 1 and 3 months (additional VF test at 6 months) after stroke onset in the patient group. The control group also underwent RS-fMRI and a Humphrey VF test. The changes in RSFCs and VF scores (VFSs) over time and their correlations were investigated. RESULTS: In 32 patients (65±10 years, 25 men), the VFSs were lower and the interhemispheric RSFC in the visual cortices was decreased compared to the control group (n=15, 62±6 years, seven men). The VFSs and interhemispheric RSFC in the visual cortex increased mainly within the first month after stroke onset. The interhemispheric RSFC and VFSs were positively correlated at 1 month after stroke onset. Moreover, the interhemispheric RSFCs in the visual cortex within 1 week were positively correlated with the follow-up VFSs. CONCLUSIONS: Interhemispheric RSFCs in the visual cortices within 1 week after stroke onset may be a useful biomarker to predict long-term VFD recovery.

Different Cortical Thinning Patterns Depending on Their Prognosis in Individuals with Subjective Cognitive Decline

BACKGROUND AND PURPOSE: Subjective cognitive decline (SCD) may be the first stage corresponding to subtle cognitive changes in patients with Alzheimer's disease (AD) spectrum disorders. We evaluated the differences in cortical thinning patterns among patients with SCD who progressed to mild cognitive impairment or dementia (pSCD), those who remained stable (sSCD), and healthy normal controls (NCs).METHODS: We retrospectively recruited SCD subjects (14 pSCD and 21 sSCD cases) and 29 NCs. Structural 3-dimensional-T1-weighted magnetic resonance imaging was performed using a single 1.5 Tesla scanner. Freesurfer software was used to map cortical thickness for group comparisons.RESULTS: Compared with NC group, the sSCD group showed diffuse cortical atrophy associated with bilateral fronto-parieto-temporal area. The pSCD group showed further characteristic cortical atrophy in AD-vulnerable regions including the inferior parieto-temporal and middle temporal areas. Cortical thinning in the bilateral medial frontal areas was observed in patients with sSCD and involved the right inferior temporal and left precentral areas in those with pSCD.CONCLUSIONS: Our study showed that SCD subjects exhibit different cortical thinning patterns depending on their prognosis.

Safety and Efficacy of Anti-dementia Agents in the Extremely Elderly Patients with Dementia

BACKGROUND: There are debates on representation and generalizability of previous randomized controlled trials about anti-dementia agents in the oldest old population. In this context, we aimed to investigate the efficacy and safety of anti-dementia agents in the very elderly patients with dementia. METHODS: We conducted a retrospective study of patients with dementia 1) who were 85 years or older, 2) got started anti-dementia agents, and 3) went through follow-up evaluation about one year thereafter. As a control, patients with dementia who were less than 85 years old with similar inclusion criteria were randomly selected during the same period. The adverse drug effects and discontinuation rates were investigated with self-reported complaint after starting or increasing anti-dementia drugs. For efficacy outcome, we also analyzed the change in neuropsychological results during follow-up period. RESULTS: A total of 77 dementia patients who were at least 85 years were enrolled. As a control group, 78 patients with dementia who were younger than 85 was analyzed. The adverse drug effects were observed in 26 (33.3%) patients in the younger old and in 26 (33.8%) in the oldest old (P = 0.095). Twenty-one patients (26.9%) in the younger old group and 13 patients (16.9%) in the oldest old group discontinued their medication (P = 0.131). There were no differences between the two groups about changes of Mini-Mental State Examination and Instrumental Activity of Daily Living scores over time. CONCLUSION: The use of anti-dementia agents in the oldest old dementia patients may be safe and effective as the younger old dementia patients.

Carotid Ultrasonography vs. CT or MR Angiography in the Diagnosis of the Stenosis of Vertebral Artery Origins

BACKGROUND: The origin of the vertebral artery (VA) is prone to be misinterpreted as having focal stenosis on computed tomography angiography (CTA) or magnetic resonance angiography (MRA) due to artifacts. Ultrasonography may be a valuable technique to reveal stenosis of the VA origin. We compared the findings for the VA origin from CTA or MRA with those from ultrasonotraphy. METHODS: We consecutively enrolled patients who underwent angiography (CTA or MRA) and carotid ultrasonography. The V2 and V1 portions of the VA were insonated to evaluate the presence of plaque or steno-occlusion. CTA or MRA data were evaluated. Stenosis or occlusion of the VA origin was categorized as present or absent. The results from the two methods were compared. RESULTS: The mean age of the 73 investigated patients was 61.1 years, and 46 (63.0%) of them were male. Among the 22 patients with steno-occlusion of the right VA on CTA or MRA, only six had stenosis on ultrasonography. Regarding the left VA, only four patients among 16 who showed steno-occlusion on CTA or MRA had steno-occlusion on ultrasonography. The level of agreement between the two methods was 82.2% on the left side and 75.3% on the right side. There were no clinical differences between the patients with and without false-positive results on CTA or MRA. CONCLUSIONS: In 16.4% (left) and 21.9% (right) of all patients, lumens with steno-occlusions observed on CTA or MRA were revealed as normal on ultrasonography. The diagnosis of VA origins could be improved by applying these two methods complementarily.

Previous and Recent Evidence of Endovascular Therapy in Acute Ischemic Stroke / 신경중재치료의학

The ideal therapy of acute ischemic stroke is achieved by early recanalization that finally leads to good clinical outcome. The recombinant intravenous tissue plasminogen activator (rtPA) within 4.5 hours was approved as an important thrombolytic treatment. However, the recanalization rate was low in patients with a large artery occlusion. The efficacy of intravenous rtPA regarding recanalization of a large artery occlusion was limited. In several clinical trials, pharmacological and mechanical intra-arterial thrombolytic therapy showed improved recanalization rates, but the favorable outcome had not been achieved. Through those trials and errors, researchers have learned that speed of treatment initiation, patient selection by documentation of large artery occlusion and the use of effective devices could be crucial for good clinical outcomes. Finally, five recent randomized controlled trials of endovascular therapy compared to standard medical care have been published. The superiority of endovascular thrombolysis to standard medical care was proved. In this article, we reviewed previous and recent clinical evidence about endovascular thrombolytic therapy of acute ischemic stroke.

White Matter Hyperintensity in Ischemic Stroke Patients: It May Regress Over Time / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) are frequently observed on MRI in ischemic stroke patients as well as in normal elderly individuals. Besides the progression of WMH, the regression of WMH has been rarely reported. Thus, we aimed to investigate how WMH change over time in patients with ischemic stroke, particularly focusing on regression. METHODS: We enrolled ischemic stroke patients who underwent brain MRI more than twice with at least a 6 month time-interval. Based on T2-weighted or FLAIR MRI, WMH were visually assessed, followed by semiautomatic volume measurement. Progression or regression of WMH change was defined when 0.25 cc increase or decrease was observed and it was also combined with visible change. A statistical analysis was performed on the pattern of WMH change over time and factors associated with change. RESULTS: A total of 100 patients were enrolled. Their age (mean+/-SD) was 67.5+/-11.8 years and 63 were male. The imaging time-interval (mean) was 28.0 months. WMH progressed in 27, regressed in 9 and progressed in distinctive regions and regressed in others in 5 patients. A multiple logistic regression model showed that age (odds ratio[OR] 2.51, 90% confidence interval[CI] 1.056-5.958), male gender (OR 2.957, 95% CI 1.051-9.037), large vessel disease (OR 1.955, 95% CI 1.171-3.366), and renal dysfunction (OR 2.900, 90% CI 1.045-8.046) were associated with progression. Regarding regression, no significant factor was found in the multivariate analysis. CONCLUSIONS: In 21.5% of ischemic stroke patients, regression of WMH was observed. WMH progression was observed in a third of ischemic stroke patients.

Acute Lacunar Infarction Adjacent to the Pre-existing Cerebral Microbleeds

No abstract available.

One-Year Follow-up Pilot Study for Dementia Diagnosis in Elderly with Recall Score of 0 in Korean-version of Mini-Mental State Examination

BACKGROUND: The early stage of Alzheimer disease might show early memory impairment with normal general cognitive function. Our study aimed to investigate elderly with normal Korean version of mini-mental state examination (K-MMSE) score and recall score of 0 for 1 year. We predicted that the patients would show different characteristics and would progress more rapidly compared with normal controls. METHODS: This study was based on the data from complete enumeration survey of Mapo-gu Regional Center for Dementia in 2009. We divided all subjects into three groups: subjects with normal K-MMSE scores and recall score of 0 were group 1-1 (n=152), subjects with abnormal K-MMSE scores were group 1-2 (n=64) and subjects with normal K-MMSE scores and recall score of 1 to 3 were group 1-3 (n=941). We compared basic demographics and social characteristics among the three groups. After 1 year (2010), the subjects in group 1-1 (90 out of 152) underwent follow-up examinations for dementia diagnosis. They were also divided into three groups (2-1, 2-2, 2-3) according to K-MMSE and recall scores. RESULTS: Group 1-1 showed different baseline characteristics compared with normal controls. After 1 year, 25.5% (23 out of 90) of the group 2-1 were diagnosed as mild cognitive impairment (n=16) or dementia (n=7). CONCLUSION: Our study suggested that subjects with normal K-MMSE scores but recall score of 0 are not entirely "normal". Further detailed evaluation might be needed if memory impairment is suspicious although the K-MMSE scores are within normal range.

Physicians' Attitudes Toward Guidelines for Stroke: A Survey of Korean Neurologists / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Clinical practice guidelines (CPGs) are regarded as an essential guidance tool for practicing physicians. We surveyed physicians in Korea in order to evaluate their attitudes toward the Korean CPGs for stroke. METHODS: We obtained participation agreement for our survey from 27 centers of the 33 most actively contributing to the Korean Stroke Registry. A total of 174 neurologists participated in a questionnaire interview regarding their attitudes toward CPGs for stroke. RESULTS: Of 174 participating neurologists, 65 (37.4%) were stroke neurologists. The average age was 33.6+/-7.1 and 49 (28.2%) were female. Most of the respondents held positive attitudes and opinions regarding the use of the guidelines, whereas only a small percentage (14.9%) responded negatively. More than 60% of the physicians in the survey reported adherence to the Korean CPGs in dyslipidemia management for the secondary prevention of stroke. CONCLUSIONS: The positive attitudes and opinions toward the guidelines imply that physicians' attitudes should not be regarded as a potential barrier to the implementation of Korean CPGs for stroke practiced by general physicians.

Clinical and Radiological Characteristics of Acute Ischemic Stroke Consulted from Nonneurology Departments

BACKGROUND: An acute ischemic infarction can occur in patients admitted to a nonneurology department, which can result in a delay in the diagnosis that could produce a poor outcome. The aim of this study was to identify the clinical and radiologic features of ischemic stroke diagnosed during consultations in nonneurology departments. METHODS: Acute ischemic stroke patients who were admitted to a neurology department or who were diagnosed after a consultation to a neurology department between October 2007 and February 2009 were enrolled. Acute ischemic stroke was diagnosed by a stroke neurologist with the aid of diffusion-weighted MRI. Clinical variables [age, sex, risk factors, initial score on the National Institutes of Health Stroke Scale, stroke subtype, and modified Rankin scale (mRS) score at 3 months] were obtained. Poor clinical outcome was defined as a mRS score of 3-6. Stroke lesion types based on MRI were classified into single vascular territory, multiple vascular territories, and multiple circulations. RESULTS: In total, 340 patients were enrolled, 84 (24.7%) of whom were diagnosed in nonneurology departments. Among the 84 consultations, 57 cases were symptomatic ischemic strokes, and 27 cases exhibited irrelevant acute ischemic lesions. With respect to the stroke subtype, other cause (10.7% vs 4.8%) and undetermined cause (42.9% vs 20.7%) were more common in the nonneurology department patients (p<0.0001). Acute ischemic strokes in multiple circulations were also more common in those from nonneurology departments (44.0% vs 11.0%, p<0.0001), along with higher high-sensitivity C-reactive protein levels. A poor clinical outcome was more common among patients in the nonneurology departments than among those in the neurology department (75.0% vs 27.5%, p<0.0001). CONCLUSIONS: Ischemic strokes from nonneurology departments tend to appear as nonlocalizing neurologic symptoms and spread in multiple circulations, and are associated with a worse outcome than those from neurology departments.

Clinical and Radiological Characteristics of Ischemic Stroke in the 80 Year-Old or Older: A Single Center Study

BACKGROUND: The risk profiles and stroke presentations may differ between elderly stroke patients and their younger counterparts. The most appropriate stroke-management regime for a better outcome can only be achieved with knowledge of the characteristics of elderly stroke patients. This study compared the clinical and radiological characteristics of elderly (> or =80 years) ischemic stroke patients with those aged 80 years (40.0% vs. 63.3%; p=0.001), while their initial NIHSS score was higher (median, 4 vs. 3; p=0.033). Furthermore, an unclear stroke onset (46.4% vs. 32.8%; p=0.049) and clinicoradiological discrepancies (13.8% vs. 5.7%; p=0.044) were more common among the elderly. The proportions of subjects with stroke of undetermined cause (30.0% vs. 18.0%; p=0.019) and multiple circulation infarctions (23.3% vs. 12.6%, p=0.030) were higher among the elderly. A favorable outcome (mRS score of 0 or 1) was more common in the younger stroke patients (57.5% vs. 25.9%, p<0.0001). Multivariate analysis revealed that younger age, male gender, and initial stroke severity were significantly associated with a favorable outcome. CONCLUSIONS: These results indicate that stroke presentation in the elderly differs from that of their younger counterparts in terms of clinical and radiological variables.

Statin Prescription Adhered to Guidelines for Patients Hospitalized due to Acute Ischemic Stroke or Transient Ischemic Attack

BACKGROUND AND PURPOSE: Secondary stroke prevention guidelines recommend statins for the management of dyslipidemia in ischemic stroke and transient ischemic attack (TIA). This study assessed the guideline-based statin prescription (GBSP) rate in Korea and the associated physician and patient factors. METHODS: A survey was conducted to assess Korean neurologists' knowledge of and attitude toward the current dyslipidemia management guidelines. The characteristics and discharge statin prescription for all consecutive patients with acute ischemic stroke or TIA treated by participating neurologists during the 6 months prior to the survey were abstracted. Using algorithms to determine GBSP, we assessed the rate and independent factors of GBSP. RESULTS: Of the 174 participating neurologists, 79 (45.4%) were categorized as a higher-level knowledge group. For the 4407 patients (mean age, 66.4 years; female, 42.5%; 90.6% with ischemic stroke and 9.4% with TIA) enrolled in this study, the GBSP rate at discharge was 78.6%. The GBSP rate increased significantly with increasing physician knowledge level (test for trend, p<0.0001), and was higher among patients treated by the higher-level knowledge group than for those treated by the lower-level knowledge group (81.6% vs. 74.7%; unadjusted p<0.0001 and adjusted p=0.045). Other independent factors associated with a higher GBSP rate were hypercholesterolemia and higher low-density lipoprotein cholesterol level, while those associated with a lower GBSP rate were cardioembolism, undetermined etiology due to negative or incomplete work-up, other determined etiology, and TIA presentation. CONCLUSIONS: More than three-quarters of acute ischemic stroke survivors and TIA patients receive a GBSP at discharge, and this proportion would be further improved by improving the knowledge of dyslipidemia management guidelines among neurologists.

A Semi-Automated Method for Measuring White Matter Hyperintensity Volume

BACKGROUND: White matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) have been considered as a reliable biomarker of small vessel damages. To evaluate the severity of WMHs, it is vital to develop reliable methods to measure the volume of WMHs. We applied open source software to measure WMH volume in the semi-automated way, and tested the reliability and validity by comparing with the commonly used qualitative rating scale. METHODS: Twenty five subjects with variable WMHs were recruited. ANALYZE 10.0 was used for the image processing and volumetric measurement of WMHs. The inhomogeneity and artifacts of signal were corrected with Insight Segmentation and Registration Toolkit in ANALYZE. For the gold standard of the WMH volumetric measurement, threshold method was applied with consensus of manual editing on each slice of the MRI images by two raters. Histogram of the all slices of the Fluid Attenuated Inversion Recovery (FLAIR) MRI was generated to calculate the optimal voxel intensity of threshold, and the lowest voxel threshold was decided as the mean+1.4 SD. The volumes of WMHs were generated by multiplying the area and the thickness of each slice. Inter- and intrarater reliability of the semi-automated volumetric and Scheltens'methods, and the association between the individual methods were analyzed. RESULTS: The semi-automated WMH volume at the threshold of 1.4 SD as well as the gold standard volume was well correlated with the Scheltens' visual scale (r=0.75, p<0.001). The semi-automated volumetry showed the excellent intra-rater (ICC=0.9929; 95% CI, 0.9840-0.9968) and inter-rater reliability (ICC=0.9830; 95% CI, 0.9620-0.9925), superior to the Scheltens' visual rating scale. CONCLUSIONS: The semi-automated volume measurement of the WMHs with Analyze was a valid and a reliable method to quantify subcortical white matter damages of various etiologies.

Coexisting Carotid Atherosclerosis in Patients with Intracranial Small- or Large-Vessel Disease

BACKGROUND AND PURPOSE: The coexistence of carotid atherosclerosis in ischemic stroke patients with small-vessel disease (SVD) or intracranial large-vessel disease (ICLVD) was investigated using carotid duplex ultrasonography, and whether its coexistence affected the clinical prognosis was determined. METHODS: Ischemic stroke patients with SVD or ICLVD were enrolled (n=103). Risk factors, demographic data, and National Institutes of Health Stroke Scale (NIHSS) scores were obtained for all of the subjects. Early neurological progression was defined by an increase in NIHSS score during the first 7 days. Carotid ultrasonography was performed to measure the intima-media thickness (IMT) and carotid plaques. RESULTS: Among the 103 patients who were retrospectively enrolled in this study (56 with SVD and 47 with ICLVD), 66 (64.1%) had an atherosclerotic plaque and 23 (22.3%) had increased IMT. Increased IMT was observed more frequently in ICLVD than in SVD [15/47 (31.9%) vs. 8/56 (14.3%), p=0.032]. An atherosclerotic plaque was observed on subsequent carotid ultrasonographic examination in 28 (50%) of the 56 patients whose computed tomography angiography scans of the neck vessels were interpreted as normal. There was no association between presence of atherosclerotic change and early neurologic progression (p=0.94). CONCLUSIONS: A coexisting atherosclerotic plaque or increased IMT was observed in 71.8% of patients with SVD or ICLVD. Whether the coexistence of carotid atherosclerotic change with either of these conditions affects the clinical prognosis remains to be elucidated.

Focused Update of Korean Clinical Practice Guidelines for the Thrombolysis in Acute Stroke Management / 대한뇌졸중학회지

Since the release of first Korean Clinical Practice Guideline of Stroke in 2009, many important new evidences have emerged in the field of thrombolytic therapy. Among the recent developments are the extended therapeutic time window of intravenous (IV) tissue plasminogen activator (tPA) up to 4.5 hours after onset, and the efforts for the wider application of IV thrombolysis to patients with minor stroke and elderly patients over 80 years old. Debates about the optimal dose of IV tPA according to the ethnic population is still ongoing. Further evidences for the efficacy of intra-arterial thrombolysis have also accumulated, including the application of various novel mechanical devices with promising results. Thus update of guideline became necessary and we revise the acute stroke management guideline, focusing on the thrombolytic therapy.

A Unique Ultrasonographic Finding of Carotid Thrombus in a Patient with Acute Cardiogenic Cerebral Infarction / 대한뇌졸중학회지

In patients with acute ischemic stroke, carotid duplex ultrasonography has been used to assess atherosclerotic lesions at the extracranial carotid artery. We reported a unique sonographic finding of carotid artery thrombus in a patient with acute cardioembolic stroke and atrial fibrillation. An 81-year-old woman with atrial fibrillation was presented with dysarthria and left side hemiparesis. She had undergone surgical thrombectomy and angioplasty for her right brachial artery occlusion four days before the stroke onset. Diffusion-weighted MRI revealed multiple territorial infarctions suggestive of acute cardio-embolic stroke. CT angiography showed an occlusion of the right common carotid artery. On B-mode ultrasonography, longitudinal intraluminal tortuous cylinderic oscillating thrombus was observed on the right distal common carotid artery to the proximal internal carotid artery. This case illustrates a unique ultrasonographic finding of acute cardiogenic thrombus in the extracranial carotid artery.

Altered Consciousness After Acute Lacunar Infarction of the Corona Radiata in Patients With Severe White Matter Change

With an increasing proportion of the elderly, dementia due to severe cerebral white matter change is frequently observed. Because these patients cannot express their symptoms effectively, the recognition of stroke can be delayed. In addition, clinical characteristics of their stroke might be different. We reported on three patients with severe leukoaraiosis, who exhibited altered consciousness after acute lacunar infarction in the corona radiata. This clinico-radiological discrepancy may have resulted from different susceptibility to ischemia in patients with severe white matter change.

Anatomical Correlates of Interlocking Pentagon Drawing

BACKGROUND: The interlocking pentagon drawing test, a part of the Mini-Mental State Examination (MMSE), is a widely used clinical practice to measure visuoconstructional ability of dementia patients. We investigated the anatomical structures of brain associated with pentagon drawing in subjects with mild to moderate Alzheimer's disease (AD) by using voxel-based morphometry (VBM). METHODS: Medical records of forty-four AD patients were reviewed and a 1.5 T SPGR 3D image data were used for VBM analysis. A voxel-based multiple regression analysis was used to investigate correlation between gray matter loss and pentagon drawing performance of AD patients. The correlations between pentagon drawing score and MMSE score were evaluated by Spearman correlation analysis. RESULTS: There was a positive correlation between the interlocking pentagon copying scores and the MMSE scores (r=0.448, p=0.002). The lower the scores of interlocking pentagon copying were, the more severe the atrophy of right inferior frontal gyrus became ([x, y, z]=[52, 39, 3], Broadmann area 45, and z score=3.86). CONCLUSIONS: The performance of interlocking pentagon drawing is associated with a general cognitive function in patients with mild-to-moderate Alzheimer's disease. It is also associated with the atrophy of the right inferior frontal gyrus.