Jae-Hyeok Heo

Panax Ginseng Enhances Cognitive Performance in Alzheimer Disease

Recent experimental evidences suggest protective and trophic effects of ginseng in the memory function of Alzheimer disease (AD). Thus, we investigated the clinical efficacy of Panax ginseng in the cognitive performance of AD patients in an open-label study. Consecutive AD patients were randomly assigned to the ginseng (n=58) or the control group (n=39), and the ginseng group was treated with Panax ginseng powder (4.5 g/d) for 12 weeks. Cognitive performances were monitored using the mini-mental state examination (MMSE) and Alzheimer disease assessment scale (ADAS) during 12 weeks of the ginseng treatment and at 12 weeks after the ginseng discontinuation. MMSE and ADAS scales showed no baseline difference between the groups. After ginseng treatment, the cognitive subscale of ADAS and the MMSE score began to show improvements and continued up to 12 weeks (P=0.029 and P=0.009 vs. baseline, respectively). After discontinuing ginseng, the improved ADAS and MMSE scores declined to the levels of the control group. These results suggest that Panax ginseng is clinically effective in the cognitive performance of AD patients (ClinicalTrials.gov Identifier: NCT00391833).

The effects of bilateral Subthalamic Nucleus Deep Brain Stimulation (STN DBS) on cognition in Parkinson disease

The effects of subthalamic nucleus (STN) stimulation on cognition and mood have not been well established. The authors estimated cognitive and mood effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinsons disease (PD) at 6 months and 1 year postoperatively. Forty-six patients were recruited from the Movement Disorder Center at Seoul National University Hospital. Neuropsychologic tests were performed three times, before, 6 months after, and 1 year after surgery. Mean patient age was 58 and mean education duration 8 years. Eighteen of the 46 patients were men. The instruments used for assessing cognitive functions were; the Mini-Mental Status Examination (MMSE), the Trail Making Test (TMT), the Korean Boston Naming Test (K-BNT), the Rey-Kim Memory Battery, the Grooved pegboard test, the Stroop test, a fluency test, the Wisconsin Card Sorting test (WCST), and the Beck depression inventory (BDI). Of these tests, the verbal memory test, the Stroop test, and the fluency test showed statistically significant changes. The verbal memory test using the Rey-Kim memory battery showed a decline in delayed recall and recognition at 6 months and 1 year postoperatively, whereas nonverbal memory showed no meaningful change. In terms of frontal lobe function tests, Stroop test and fluency test findings were found to be aggravated at 6 months and this continued at 1 year postoperatively. Previous studies have consistently reported a reduction in verbal fluency and improvements in self-reported symptoms of depression after STN DBS. However, in the present study, Beck depression inventory (B.D.I.) was not significantly changed. Other tests, namely, MMSE, TMT, K-BNT, Grooved pegboard test, and the WCST also failed to show significant changes. Of the baseline characteristics, age at onset, number of years in full-time education, and L-dopa equivalent dosage were found to be correlated with a postoperative decline in neuropsychological test results. The correlation of motor improvement and cognitive deterioration was not significant, which suggests that the stimulation effect is rather confined to the motor-related part in the STN. In conclusion, bilateral STN DBS in Parkinsons disease did not lead to a significant global deterioration in cognitive function. However, our findings suggest that it has minor detrimental long-term impacts on memory and frontal lobe function.

Effects of human neural stem cell transplantation in canine spinal cord hemisection.

Abstract Objectives: Previous works have reported that the transplantation of neural stem cells (NSCs) may improve functional recovery after spinal cord injury (SCI), but these results have been mainly obtained in rat models. In the present work, the authors sought to determine whether the transplantation of human NSCs improves functional outcome in a canine SCI model and whether transplanted NSCs survive and differentiate. Methods: Human NSCs (HB1. F3 clone) were used in this work. Lateral hemisection at the L2 level was performed in dogs and either (1) Matrigel (200 μl) alone as a growth-promoting matrix or (2) Matrigel seeded with human NSCs (107 cells/200 μl) were transplanted into hemisected gaps. Using a canine hind limb locomotor scale, functional outcomes were assessed over 12 weeks. Immunofluorescence staining was performed to examine cell survival, differentiation and axonal regeneration. Results: Compared with dogs treated with Matrigel alone, dogs treated with Matrigel + human NSCs showed significantly better functional recovery (10.3 ± 0.7 versus 15.6 ± 0.7, respectively, at 12 weeks; p<0.05). Human nuclei-positive cells were found mainly near hemisected areas in dogs treated with Matrigel + NSCs. In addition, colocalization of human nuclei and neuronal nuclei or myelin basic protein was clearly observed. Moreover, the Matrigel + NSC group showed more ascending sensory axon regeneration. Conclusions: The transplantation of human NSCs has beneficial effects on functional recovery after SCI, and these NSCs were found to differentiate into mature neurons and/or oligodendrocytes. These results provide baseline data for future clinical applications.

Improvement of Cognitive Deficit in Alzheimer's Disease Patients by Long Term Treatment with Korean Red Ginseng

A 24-week randomized open-label study with Korean red ginseng (KRG) showed cognitive benefits in patients with Alzheimer’s disease. To further determine long-term effect of KRG, the subjects were recruited to be followed up to 2 yr. Cognitive function was evaluated every 12 wk using the Alzheimer’s Disease Assessment Scale (ADAS) and the Korean version of the Mini Mental Status Examination (K-MMSE) with the maintaining dose of 4.5 g or 9.0 g KRG per d. At 24 wk, there had been a significant improvement in KRG-treated groups. In the long-term evaluation of the efficacy of KRG after 24 wk, the improved MMSE score remained without significant decline at the 48th and 96th wk. ADAS-cog showed similar findings. Maximum improvement was found around week 24. In conclusion, the effect of KRG on cognitive functions was sustained for 2 yr follow-up, indicating feasible efficacies of long-term follow-up for Alzheimer’s disease.

The possible role of antioxidant vitamin C in Alzheimer's disease treatment and prevention.

Oxidative stress is suggested to play a major role in the pathogenesis of Alzheimer’s disease (AD). Among the antioxidants, vitamin C has been regarded as the most important one in neural tissue. It also decreases β-amyloid generation and acetylcholinesterase activity and prevents endothelial dysfunction by regulating nitric oxide, a newly discovered factor in the pathogenesis and progression of AD. However, clinical trials using antioxidants, including vitamin C, in patients with AD yielded equivocal results. The current article discusses the relevance of vitamin C in the cellular and molecular pathogenesis of AD and explores its therapeutic potential against this neurodegenerative disorder.

White Matter Hyperintensities and Cognitive Dysfunction in Alzheimer Disease

The effect of white matter lesions in magnetic resonance imaging or vascular atherosclerosis on cognitive function is not fully understood in Alzheimer disease (AD). In this investigation, we examined the influence of white matter lesions on cognitive decline in AD. A total of 142 patients with AD (44 men, mean age 65.7 + 7.6 years; mean education period 7.8 + 5.0 years) were included. Patients were divided into 4 groups based on the severities of white matter hyperintensities (WMH) in brain magnetic resonance images (MRI) using Fazekas scale. Cognitive functions were determined using the Korean version of the Mini-Mental State Examination (K-MMSE) and the Clinical Dementia Rating (CDR) scale before acetylcholinesterase inhibitors were administered. Of the 142 patients, 30% (43/142) had no white matter signal abnormality (grade 0). Fourteen percentage (20/142) were grade 1, 42% (59/142) grade 2, and 14% (20/142) were grade 3. Mean K-MMSE scores declined as MRI grades increased to grade 2 and 3 compared to grade 0 (P < .01). Clinical Dementia Ratings were also aggravated by MRI grade. These results remained significant after adjusting for compounding factors affecting cognitive functions; sex, age, number of years in full-time education, hypertension, diabetes, hypercholesterolemia, smoking, and atrial fibrillation. The presence of WMHs were associated with score of MMSE and CDR impairment in patients with AD. These features could be a correctable factor hastening cognitive decline in AD.

Spatial Distribution of Glucose Hypometabolism Induced by Intracerebroventricular Streptozotocin in Monkeys

Intracerebroventricular injection of streptozotocin (icv-STZ) in rodents induces cellular and behavioral features mimicking Alzheimers disease (AD). However, the effect of icv-STZ in terms of regional cerebral glucose metabolism has not yet been examined in vivo. Given that regionally specific hypometabolism of glucose is a consistent neuroimaging marker in early AD, we monitored 18F-deoxyglucose uptake using a high-resolution micro-PET after icv-STZ in non-human primates. Two cynomolgus monkeys (Macaca fascicularis) received STZ (2 mg/kg), and another two were given normal saline as controls, at the cerebellomedullary cistern (CM) three times (day 1, 7, and 14). FDG-PET, as well as MRI for structural evaluation, was performed immediately before, six weeks after, and 12 weeks after the first icv injection. In the STZ group, FDG uptake decreased significantly in comparison to the pre-injection baseline, at the precuneus, the posterior cingulate, and medial temporal cortices. Increase in sulcal markings suggesting brain atrophy was observed by MRI at six weeks post-injection. The structural changes normalized at 12 weeks, but the reduced FDG uptake persisted at the same loci. The cortical distribution of glucose hypometabolism was similar to that at early stages of AD patients. The findings demonstrate that the effect of icv-STZ is regionally specific, lending further support for the method as a model of AD pathogenesis.

Neuro-Behcet's disease mimicking multiple brain tumors: Diffusion-weighted MR study and literature review

A 47-year-old man with Behcets disease presented with a five day history of right side weakness and dysarthria. Ten years ago, he was diagnosed as Behcets disease. Since then, he was treated with low dose steroids. T1-weighted magnetic resonance images with gadolinium injection revealed ring enhancing lesions with internal hypointensities at the left side of the pons and at the left parietal cortex suggesting multiple metastatic tumors. Diffusion-weighted image and ADC map revealed central hyperintensity on diffusion with low ADC values at both lesions. The histopathology of stereotactic biopsy specimen showed frequent perivascular lymphocytic cuffings, focal necrotic lesions and reactive gliosis. The most common neuropathologic findings in neuro-Behcets disease are focal necrotic lesions, but the location in cerebral cortex has not been reported before. Long term steroid therapy and antibiotics were administered and the patient recovered gradually. Neuro-Behcets disease could be presented as brain tumor like lesion, and stereotactic biopsy should be considered in such situation.

The efficacy of combined estrogen and buspirone treatment in olivopontocerebellar atrophy

BACKGROUND Olivopontocerebellar atrophy (OPCA) is a chronic neurodegenerative disease with symptoms of cerebellar ataxia, parkinsonism, autonomic disturbances and ophthalmoplegia. Buspirone, a 5-HT1(A) agonist could constitute a symptomatic improvement in cerebellar dysfunction whereas estrogen has been investigated for neuroprotection. We conducted an open-labeled pilot trial to assess the efficacy of estrogen with buspirone treatment. PATIENTS AND METHODS Eighteen patients (7 male and 11 female) with OPCA were randomized into the buspirone (15 mg/day, n=9), or the combined treatment group (estrogen, 0.625 mg/d plus buspirone, n=9). For the clinical rating, International Cooperative Ataxia Rating Scale (ICARS) was used and dysarthria, gaze evoked nystagmus, finger to nose, pronation-supination alternating movement, knee-tibia test, and gait speed were evaluated for 12 months. RESULTS Buspirone-treated group showed improvements in finger to nose and pronation-supination alternating movement test (p=0.046 and p=0.025, respectively). The combination group (Estrogen+buspirone), however, showed no improvement in cerebellar sub-scales compared to the baseline. CONCLUSIONS Buspirone treatment showed feasible efficacies for OPCA, while the combined treatment of estrogen and buspirone failed to improve, suggesting estrogen may not have further benefit in cerebellar dysfunction.

Heat-processed ginseng enhances the cognitive function in patients with moderately severe Alzheimer's disease

Abstract Objectives Ginseng has been reported to improve cognitive function in animals and in healthy and cognitively impaired individuals. In this study, we investigated the efficacy of a heat-processed form of ginseng that contains more potent ginsenosides than raw ginseng in the treatment of cognitive impairment in patients with moderately severe Alzheimers disease (AD). Methods Forty patients with AD were randomized into one of three different dose groups or the control group as follows: 1.5 g/day (n = 10), 3 g/day (n = 10), and 4.5 g/day (n = 10) groups, or control (n = 10). The Alzheimers Disease Assessment Scale (ADAS) and Mini-Mental State Examination (MMSE) were used to assess cognitive function for 24 weeks. Results The treatment groups showed significant improvement on the MMSE and ADAS. Patients with higher dose group (4.5 g/day) showed improvements in ADAS cognitive, ADAS non-cognitive, and MMSE score as early as at 12 weeks, which sustained for 24-week follow-up. Discussion These results demonstrate the potential efficacy of a heat-processed form of ginseng on cognitive function and behavioral symptoms in patients with moderately severe AD.