Body Fat Mass and Risk of Cerebrovascular Lesions: The PRESENT (Prevention of Stroke and Dementia) Project.

Obesity is known to increase the risk of stroke. It is unclear whether high absolute fat mass (FM) increases the risk of stroke independently. We studied the correlation between FM and silent brain infarction/white matter change (SI/WMC) using brain computed tomography. We selected subjects from the local government health promotion project. We randomly selected a target population that had never been diagnosed with stroke or dementia. FM was measured by bioelectrical impedance analysis (BIA). We divided the subjects into three groups according to the FM (gender-specific tertiles [GTx]). Seven hundred and twenty-two subjects (321 men) between 50 and 75 years of age were recruited. The overall odds ratio (OR) of SI/WMC was 2.23 (95% confidence interval (CI), 1.34-3.71; p = 0.002) times higher in the 37th to 100th percentiles (GT3) than in the first to 32nd percentiles (GT1). When men and women were separated, the OR of GT3 was 1.35 (CI, 0.62-2.94; p = 0.45) in men and 3.2 (CI, 1.60-6.40; p = 0.001) in women. The findings were not found to be statistically significant after adjusting for the well-known stroke risk factors. When the subjects were divided into a high FM (HFMG, GT3) and low FM group (LFMG, GT1 + GT2), the HFMG showed an increased OR of SI/WMC in women. Similar results were seen after adjusted (overall: OR, 1.38; CI, 0.85-2.25, p = 0.198; men: OR, 0.93; CI, 0.422-2.051; p = 0.86; women: OR, 2.02; CI, 1.06-3.86; p = 0.03). The findings suggest that high FM may be an independent risk factor for ischemic stroke among adults free from stroke and dementia, especially in women.

Bone mineral loss and cognitive impairment: The PRESENT project.

Low bone mineral density (BMD) is correlated with Alzheimer's disease and its severity, but the association remains unclear in adults (≥50 years) without a history of stroke or dementia.We assessed BMD and cognitive function using the Mini-Mental Status Examination (MMSE) in 650 stroke- and dementia-free subjects (≥50 years) who were recruited for an early health check-up program between January 2009 and December 2010.The mean age was 62.9 ±â€Š8.0 years and mean MMSE score was 27.6 ±â€Š3.6. A total of 361 subjects had reduced BMD: 197 (30.3%) had osteopenia and 154 (23.6%) had osteoporosis, based on criteria of world health organization. A total of 5.4% of the male subjects had osteoporosis, versus 19.8% of the female subjects. After adjusting for age, sex, education, and other possible confounding factors such as hypertension, diabetes mellitus, and smoking, the estimated odds ratio for cognitive impairment was 1.72 for the osteopenia group (95% confidence interval [CI] 1.09-2.14, P = .019) and 2.81 for the osteoporosis group (95% CI 1.78-4.45, P < .001).Low BMD is correlated with cognitive impairment in community-dwelling adults aged 50 years and above without any medical history of stroke or dementia, especially in women. A community-based, early life, preventive osteoporosis education campaign might decrease the incidence of dementia.

Stroke awareness in Korean high school students.

Public awareness is essential for the early diagnosis, treatment, and prevention of stroke. In particular, young adults represent an important avenue for increasing awareness and precluding the adoption of unhealthy, risk-increasing behaviors. This study was the first to investigate the basic knowledge of Korean adolescents about stroke and evaluate the improvement of this knowledge after an educational lecture. In total, 1269 high school students were instructed on the risk factors, symptoms, diagnosis, and management of stroke. Knowledge was evaluated before education (Pre-E), immediately after the lecture (Post-E1), and during a 2-week follow-up (Post-E2), using a questionnaire. Overall, we found that students' knowledge increased after the educational session. On the questionnaire section pertaining to stroke risk factors, out of nine possible points, the mean scores were 3.97, 5.28, and 5.10, on the Pre-E, Post-E1, and Post-E2 tests, respectively, indicating a significant improvement (p < 0.001). Additionally, students who reported that they paid attention during the lecture performed better, and scored 4.29, 6.32, and 6.40, on the Pre-E, Post-E1, and Post-E2 tests, respectively, again indicating a significant improvement (p < 0.001). Our findings indicate that incorporating a stroke education program into school curriculums will enhance the knowledge of Korean adolescents. Implementing this type of program is critical as it may reduce behavior associated with increased stroke risk, and more effort is needed to develop educational methods for engaging students and increasing their concentration during these programs.

Higher skeletal muscle mass may protect against ischemic stroke in community-dwelling adults without stroke and dementia: The PRESENT project.

BACKGROUND: It is well known that a low skeletal muscle mass (SMM) is associated with stroke. However, it is unknown whether increasing muscle mass can prevent stroke. METHODS: This community-based cross-sectional study was supported by the regional government. SMM measurements and brain computed tomography was performed in 722 stroke-free and dementia-free subjects (aged 50-75 years). Subjects were divided into quartiles (Q) by SMM, checked using the bioelectrical impedance analysis method (InBody 770, InBody, Seoul, Korea). Odds ratios (ORs) of brain white matter changes/silent infarction (WMC/SI) were calculated. The subjects were then divided into two groups by sex and evaluated. RESULTS: In the analysis of the four groups, the unadjusted ORs of Q2-Q4 were 0.616 (95% confidence interval [CI], 0.372-1.022; P = 0.061), 0.290 (CI, 0.159-0.530; P < 0.001), and 0.209 (CI, 0.108-0.403; P < 0.001) for the risk of WMC/SI. Adjusted ORs for age, hypertension, diabetes mellitus, education, hypercholesterolemia, and smoking were 0.994 (CI, 0.513-1.740; P = 0.085), 0.669 (CI, 0.329-1.362; P = 0.268), and 0.464 (CI, 0.219-0.984; P = 0.045). In the two-group (dichotomized) analysis, the unadjusted OR for the higher muscle mass groups (Q3 + Q4) was 0.313 (CI, 0.200-0.491; P < 0.001). The adjusted OR was 0.577 (CI, 0.340-0.979; P = 0.042). Considering sex, the adjusted OR were 0.351 (CI, 0.141-0.869; P = 0.024) in men and 0.771 (CI, 0.391-1.519; P = 0.452) in women. CONCLUSIONS: Our findings suggest that increased SMM may protect against WMC/SI, especially in men.

Serum Uric Acid Is Associated with Cerebral White Matter Hyperintensities in Patients with Acute Lacunar Infarction.

BACKGROUND AND PURPOSE: The Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of Transcranial Doppler (ECLIPse) study showed a significant decrease in transcranial Doppler pulsatility index (PI) with cilostazol treatment after 90 days of acute lacunar infarction. The aim of this analysis was to perform a subgroup analysis of the ECLIPse study to explore the relationship between serum uric acid (UA) and the volume of white matter hyperintensities (WMH) in patients with acute lacunar infarction. METHODS: The ECLIPse was a multicenter, randomized, double-blind, placebo-controlled study conducted in Korea. For this subgroup analysis, WMH volume was measured for those subjects for whom FLAIR or T2-weighted images were available using semiautomated computerized software. RESULTS: Of the 203 patients in 8 hospitals in the ECLIPse study, 130 in 6 hospitals were entered for this subgroup analysis. The mean age was 64.7 ± 9.95 years, and 20.8% were women. The mean WMH volume was 11.57 cm(3) (.13 to 68.45, median 4.86) and mean serum UA was 5.2 mg/dL (1.5 to 8.9). Multiple linear regression analysis revealed that age (P < .001) and serum UA (P = .013) were significantly associated with WMH volume. Age-adjusted scatterplots showed that serum UA level was positively related to WMH volume in patients with acute lacunar infarction (r = 0.275, P = .003). CONCLUSIONS: This study showed that serum UA was associated with cerebral WMH in patients with acute lacunar infarction.

Cilostazol decreases cerebral arterial pulsatility in patients with mild white matter hyperintensities: subgroup analysis from the Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of Transcranial Doppler (ECLIPse) study.

BACKGROUND: The Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of the Transcranial Doppler (ECLIPse) study showed a significant decrease in the transcranial Doppler (TCD) pulsatility index (PI) with cilostazol treatment at 90 days after acute lacunar infarction. The aim of the present study was to perform a subgroup analysis of the ECLIPse study in order to explore the effect of cilostazol in acute lacunar infarction based on cerebral white matter hyperintensities (WMH) volume. METHODS: The ECLIPse study was a multicenter, randomized, double-blind, placebo-controlled trial that evaluated the difference between the efficacy of cilostazol and a placebo to reduce the PI in patients with acute lacunar infarction using serial TCD examinations. The primary outcome was changes in the PIs of the middle cerebral artery (MCA) and basilar artery at 14 and 90 days from the baseline TCD study. For this subgroup analysis, using semi-automated computerized software, the WMH volume was measured for those subjects for whom fluid-attenuated inversion recovery (FLAIR) images were available. RESULTS: Of the 203 patients in eight hospitals in the ECLIPse study, 130 participants from six hospitals were included in this subgroup analysis. Cilostazol was given to 63 patients (48.5%) and placebo to 67 patients (51.5%). All baseline characteristics were well balanced across the two groups, and there were no significant differences in these characteristics except in the changes of PI from the baseline to the 90-day point. There was a significant decrease of TCD PIs at 90-day study from baseline in the cilostazol group (p = 0.02). The mean WMH volume was 11.57 cm(3) (0.13-68.45, median 4.86) and the mean MCA PI was 0.95 (0.62-1.50). The changes in PIs from the baseline to 14 days and to 90 days were 0.09 (-0.21 to 0.33) and 0.10 (-0.22 to 0.36). While there were no significant correlations between WMH volume and the changes in PIs, a trend of inverse correlation was observed between the WMH volume and the changes in PIs from the baseline to the 90-day point. For the subgroup analysis, the WMH volume was dichotomized based on its median value (4.90 cm(3)). Cilostazol decreased the TCD PIs significantly at the 90-day point in patients with WMH volumes ≤ 4.9 cm(3) (p = 0.002). Significant treatment effects were observed in the cilostazol group. CONCLUSIONS: This study showed that cilostazol decreased cerebral arterial pulsatility in patients with WMH. Our findings indicate the unique effect of cilostazol in small vessel disease (SVD), especially in patients with mild WMH changes. Further clinical trials focusing on WMH volume and clinical outcomes are required to assess the unique efficacy of cilostazol in SVD.

Tooth loss may predict poor cognitive function in community-dwelling adults without dementia or stroke: the PRESENT project.

Periodontal disease is a potential predictor of stroke and cognitive impairment. However, this association is unclear in adults aged 50 yr and above without a history of stroke or dementia. We evaluated the association between the number of teeth lost, indicating periodontal disease, and cognitive impairment in community-dwelling adults without any history of dementia or stroke. Dental examinations were performed on 438 adults older than 50 yr (315 females, mean age 63±7.8 yr; 123 males, mean age 61.5±8.5 yr) between January 2009 and December 2010. In the unadjusted analysis, odds ratios (OR) of cognitive impairment based on MMSE score were 2.46 (95% CI, 1.38-4.39) and 2.7 (95% CI, 1.57-4.64) for subjects who had lost 6-10 teeth and those who had lost more than 10 teeth, respectively, when compared with subjects who had lost 0-5 teeth. After adjusting for age, education level, hypertension, diabetes, hyperlipidemia, and smoking, the relationship remained significant (OR, 2.0; 95% CI, 1.08-3.69, P=0.027 for those with 6-10 teeth lost; OR, 2.26; 95% CI, 1.27-4.02, P=0.006 for those with more than 10 teeth lost). The number of teeth lost is correlated with cognitive impairment among community-dwelling adults aged 50 and above without any medical history of stroke or dementia.

Tooth loss is associated with brain white matter change and silent infarction among adults without dementia and stroke.

Periodontal disease is a predictor of stroke and cognitive impairment. The association between the number of lost teeth (an indicator of periodontal disease) and silent infarcts and cerebral white matter changes on brain CT was investigated in community-dwelling adults without dementia or stroke. Dental examination and CT were performed in 438 stroke- and dementia-free subjects older than 50 yr (mean age, 63 ± 7.9 yr), who were recruited for an early health check-up program as part of the Prevention of Stroke and Dementia (PRESENT) project between 2009 and 2010. In unadjusted analyses, the odds ratio (OR) for silent cerebral infarcts and cerebral white matter changes for subjects with 6-10 and > 10 lost teeth was 2.3 (95% CI, 1.38-4.39; P = 0.006) and 4.2 (95% CI, 1.57-5.64; P < 0.001), respectively, as compared to subjects with 0-5 lost teeth. After adjustment for age, education, hypertension, diabetes mellitus, hyperlipidemia, and smoking, the ORs were 1.7 (95% CI, 1.08-3.69; P = 0.12) and 3.9 (95% CI, 1.27-5.02; P < 0.001), respectively. These findings suggest that severe tooth loss may be a predictor of silent cerebral infarcts and cerebral white matter changes in community-dwelling, stroke- and dementia-free adults.

Effect of cilostazol in acute lacunar infarction based on pulsatility index of transcranial Doppler (ECLIPse): a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study is intended to evaluate the propensities of cilostazol to reduce the pulsatility index (PI) in patients with acute lacunar infarction using the serial transcranial Doppler (TCD) examinations. METHODS: In a multicenter, randomized, double-blind, placebo-controlled trial, patients were randomly assigned to receive either placebo or 100 mg cilostazol twice a day as well as aspirin 100 mg a day. The primary outcomes were the changes of middle cerebral artery (MCA) and basilar artery (BA) PIs at 14 and 90 days from the baseline TCD study. This study is registered with ClinicalTrials.gov (NCT00741286). RESULTS: Trial medication was given to 203 patients, with 100 receiving cilostazol and 103 receiving placebo, and 164 were included in the per-protocol analysis of the primary outcome. Results from the linear mixed model showed that significant effects were obtained for time-by-group interactions (p = 0.008 in right MCA, p = 0.015 in left MCA, p = 0.002 in BA), suggesting that changes of PIs from the baseline to the 90-day study were different across the groups. CONCLUSIONS: Cilostazol further decreased TCD PIs at 90 days from baseline compared to placebo in acute lacunar infarction. This result may be related to pleiotropic effects, such as vasodilation, beyond its antiplatelet activity.

Associated conditions and clinical significance of awake bruxism.

BACKGROUND: Awake bruxism is defined as an oral parafunctional activity that includes clenching and grinding of teeth during wakefulness. Confirming the possible related anatomy and the clinical significance of awake bruxism in geriatric hospitals is the aim of this study. METHODS: We analyzed the medical records of 503 patients who were admitted to hospital from April to June 2008. After the recognition of bruxism, the clinical, brain imaging studies and statistical parametric mapping (SPM) of brain single photon emission computed tomography were performed. RESULTS: In each disease group, five of 125 Alzheimer's disease (AD) patients (4.0%), three of 11 frontotemporal dementia (FTD) patients (27.3%), seven of 230 stroke patients (including two patients related to citalopram, 3.0%), one of 45 Parkinson's disease patients (2.2%) and four of 17 hydrocephalus patients (23.5%) had bruxism. Even though awake bruxism occurred early after stroke onset, it occurred late after AD and FTD onset. This occurred in a far advanced stage of AD, while it occurred in a moderately advanced stage of FTD. SPM analysis in AD and FTD patients with awake bruxism revealed significant hypoperfusion in frontotemporal and other subcortical structures. Surface electromyography recordings from the masseter muscle showed rhythmic regular motor activity at a rate of 1-2/s. CONCLUSION: This study suggests that awake bruxism is encountered not infrequently in various diseases in geriatric hospitals. It is frequently observed in FTD and normal pressure hydrocephalus, which characteristically shows frontal lobe dysfunction. These facts and SPM analysis show that awake bruxism can be regarded as a frontal neurological sign of various neurological disorders.

Toxic encephalopathy after taking dried seeds of Datura stramonium in two elderly subjects.

An altered mentality, or delirium, is a common medical condition of the elderly in emergency medicine or neurology clinics. Among causes of this, toxic etiology due to an anticholinergic agent is not rare. The authors present two elderly women who were brought to an emergency room because of anticholinergic syndrome. The patients displayed agitative behavior, confusion, urinary retention, dry mouth and dilated pupils within 3 h of ingesting the dried seeds of Datura stramonium which has been used as a herbal medicine or as a traditional folk remedy for relieving coughing and asthma in Korea. They were discharged with a complete recovery after receiving conservative therapy for 5 days. Physicians of emergency medicine should be mindful of anticholinergic syndrome due to herbal medicine when the elderly with a history of delirium come to a hospital.

Two cases of discontinuation syndrome following cessation of memantine.

Although memantine is widely used and generally considered safe, an abrupt cessation of memantine may result in discontinuation syndrome that can be distressing and result in decline of natural course. We report two patients who developed significant behavior disturbance after abrupt cessation of memantine. Although re-trial of memantine improves these symptoms, more additional drugs may be required to achieve previous status. Therefore, abrupt cessation of memantine should be prudent and require cautious follow up.

Induction of apoptosis signal-regulating kinase 1 and oxidative stress mediate age-dependent vulnerability to 3-nitropropionic acid in the mouse striatum.

The mitochondrial toxin, 3-nitropropionic acid (3-NP), produces age-dependent oxidative stress and selective striatal damage, which may simulate Huntington's disease starting in middle age. Recent reports showed that apoptosis signal-regulating kinase 1 (Ask1) activated by oxidative stress triggers a cell death signaling pathway. 3-NP was injected to the striatum in C57BL/6J mice. We have confirmed that striatal lesion volume and DNA fragmentation were age-dependent after 3-NP treatment. In the non-injured striatum of the middle-aged group, the protein levels of Ask1 and its active form, phosphorylated Ask1 (pAsk1), were significantly higher than in the young group. Ask1 increased more in the 3-NP injured striatum of the middle-aged group than in the non-injured striatum, and subsequently the activity of pAsk1 was significantly higher than in the young group. However, middle-aged SOD1Tg mice showed significant reductions of Ask1 and pAsk1 in the injured and the non-injured striatum compared to the middle-aged group. In particular, apoptosis signal transduction and cell death were significantly inhibited by the reduction of Ask1 expression using siRNA. Present results suggest that age-related upregulation of Ask1 and oxidative stress may mediate age-dependent striatal vulnerability to 3-NP.

Facilitation and reciprocal inhibition by imagining thumb abduction.

It is well known that motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) of the motor cortex are facilitated by voluntary muscle contraction. We evaluated the effects of imagination of movements on MEP latencies of agonist and antagonist muscles in the hand using TMS. Twenty-two healthy volunteers were studied. TMS delivered at rest and while imagining tonic abduction of the right thumb. MEPs were recorded in response to magnetic stimulation over the scalp and cervical spine (C7-T1), and central motor conduction times (CMCT) were calculated. MEPs were recorded from right abductor pollicis brevis muscle (APB) and adductor pollicis muscle (AP) simultaneously. Imagination of abduction resulted in a shortened latency of MEPs in the APB muscle, and a prolonged latency in the AP muscle. But the imagination caused no significant change in the latency of MEPs elicited by stimulation over the cervical spine. The changes of the CMCT may account for these latency changes with imagination of movement. These findings indicate that imagination of thumb abduction facilitates motoneurons of agonist muscle and has an inhibitory effect on those of antagonist muscle (reciprocal inhibition).

Aseptic Meningitis in Kikuchi's Disease.

The involvement of the nervous system in Kikuchi's disease (KD) is rare. Although some reports of meningeal involvement in KD were described in the literature from Japan, it has rarely been reported in Korea. A 23-year-old man presented with severe headache, fever, and vomiting. Cerebrospinal fluid (CSF) analysis revealed an opening pressure 300 mmH(2)O, WBC 283/mm(3), glucose 44 mg/dl and protein 86 mg/dl. Multiple tender lymph nodes on the left anterior neck were found on the 9(th) day of his hospital stay. The lymph node biopsy disclosed histopathologic features typical of KD. We report a patient with KD accompanied by aseptic meningitis, emphasizing the importance of recognizing this disorder in diagnosing patients with meningitis.

Abdominal obesity and risk of ischemic stroke: the Northern Manhattan Stroke Study.

BACKGROUND AND PURPOSE: Obesity is well recognized as a risk factor for coronary heart disease and mortality. The relationship between abdominal obesity and ischemic stroke remains less clear. Our aim was to evaluate abdominal obesity as an independent risk factor for ischemic stroke in a multiethnic community. METHODS: A population-based, incident case-control study was conducted July 1993 through June 1997 in northern Manhattan, New York, NY. Cases (n=576) of first ischemic stroke (66% >or=BORDER="0">65 years of age; 56% women; 17% whites; 26% blacks; 55% Hispanics) were enrolled and matched by age, sex, and race-ethnicity to stroke-free community controls (n=1142). All subjects were interviewed and examined and had measurements of waist-to-hip ratio (WHR). Odds ratios (ORs) of ischemic stroke were calculated with gender-specific quartiles (GQs) and gender-specific medians of WHR adjusted for stroke risk factors and body mass index (BMI). RESULTS: Compared with the first quartile, the third and fourth quartiles of WHR had an increased risk of stroke (GQ3: OR, 2.4; 95% CI, 1.5 to 3.9; GQ4: OR, 3.0; 95% CI, 1.8 to 4.8) adjusted for other risk factors and BMI. Those with WHR equal to or greater than the median had an overall OR of 3.0 (95% CI, 2.1 to 4.2) for ischemic stroke even after adjustment for other risk factors and BMI. Increased WHR was associated with a greater risk of stroke in men and women and in all race-ethnic groups. The effect of WHR was stronger among younger persons (test for heterogeneity, P<0.0002) (<65 years of age: OR, 4.4; 95%CI, 2.2 to 9.0; >or=65 years of age: OR, 2.2; 95% CI, 1.4 to 3.2). WHR was associated with an increased risk among those with and without large-artery atherosclerotic stroke. CONCLUSIONS: Abdominal obesity is an independent, potent risk factor for ischemic stroke in all race-ethnic groups. It is a stronger risk factor than BMI and has a greater effect among younger persons. Prevention of obesity and weight reduction need greater emphasis in stroke prevention programs.