A Multinational, Multicenter, Randomized, Double-Blind, Active Comparator, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Donepezil Transdermal Patch in Patients With Alzheimer’s Disease

Background@#and Purpose Oral administration of cholinesterase inhibitors is often associated with adverse gastrointestinal effects, and so developing an alternative administration route, such as transdermal, is urgently needed. The primary objective of this study was to determine the efficacy and safety of the IPI-301 donepezil transdermal patch compared with donepezil tablets (control) in mild-to-moderate probable Alzheimer’s disease (AD). @*Methods@#This prospective, randomized, double-blind, double-dummy, two-arm parallel, multicenter trial included 399 patients, among whom 303 completed the trial. For randomization, the patients were stratified based on previous treatment and donepezil dose; patients in each stratum were randomized to the test and control groups at a 1:1 ratio. @*Results@#The difference between the control group and the IPI-301 group, quantified as the Hodges–Lehmann estimate of location shift, was 0.00 (95% confidence interval: -1.00 to 1.33), with an upper limit of less than 2.02. The change in Alzheimer’s Disease Cooperative Study– Activities of Daily Living (ADCS-ADL) score differed significantly between the IPI-301 and control groups (p=0.02). However, the changes in the full-itemized ADCS-ADL scores at week 24 did not differ significantly between the two groups. There were no differences between the two groups regarding the scores for the Clinician Interview-Based Impression of Change (f0.9097), Mini-Mental State Examination (p=0.7018), Neuropsychiatric Inventory (p=0.7656), or Clinical Dementia Rating (p=0.9990). Adverse events, vital signs, and laboratory test results were comparable between the two groups. @*Conclusions@#IPI-301 was safe and efficacious in improving cognitive function in patients with mild-to-moderate AD.

Effect of Integrated Cognitive Intervention Therapy in Patients with Mild to Moderate Alzheimer's Disease

Background@#and Purpose: The effect of the integrated program comprising cognitive training, art therapy, and music therapy has not been extensively studied in patients with Alzheimer's disease (AD). The present study investigated the effect of integrated cognitive intervention therapy on cognition, and activity of daily life (ADL), and mood in patients with mild to moderate AD. @*Methods@#In this study, the data of 59 patients who met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer disease and Related Disorders Association (NINCDS-ADRDS) criteria of probable AD among those who registered at the Centenarian's Good Memory Program in Goyang from September 2014 to August 2019 were collected. We statistically analyzed the scores of Korean version of a Mini-Mental Status Examination (K-MMSE), Korean Dementia Screening Questionnaire-Cognition (KDSQ-C), Geriatric Depression Scale (GDS), Beck Anxiety Inventory (BAI), and Seoul-Instrumental Activities of Daily Living (S-IADL) of the same patients before and after the use of integrated cognitive intervention therapy. @*Results@#K-MMSE slightly increased from 18.7±4.5 to 19.7±5.0 (p<0.001) and KDSQ-C improved from 14.5±7.6 before therapy to 12.6±7.2 after therapy (p=0.001). Mean S-IADL score improved from 17.6±7.6 before therapy to 15.7±9.5 after therapy (p<0.001). Additionally, mean GDS score before the therapy was 5.6±3.5 that improved to 4.2±3.0 after the therapy (p<0.001).Mean BAI score decreased from 8.4±10.3 before therapy to 5.9±8.4 after therapy (p=0.001). @*Conclusions@#In conclusion, this study demonstrated the possibility that the use of an integrated cognitive therapy improved cognition, ADL, and mood (depression and anxiety) in patients with mild to moderate ADs.

Reliability and Validity of a Short Form of the Korean Dementia Screening Questionnaire-Cognition

A Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes: Protocol of a Multicenter, Randomized Controlled Trial

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is the most common cause of vascular dementia and a major contributor to mixed dementia. CSVD is characterized by progressive cerebral white matter changes (WMC) due to chronic low perfusion and loss of autoregulation. In addition to its antiplatelet effect, cilostazol exerts a vasodilating effect and improves endothelial function. This study aims to compare the effects of cilostazol and aspirin on changes in WMC volume in CSVD.METHODS: The comparison study of Cilostazol and aspirin on cHAnges in volume of cerebral smaLL vEssel disease white matter chaNGEs (CHALLENGE) is a double blind, randomized trial involving 19 hospitals across South Korea. Patients with moderate or severe WMC and ≥ 1 lacunar infarction detected on brain magnetic resonance imaging (MRI) are eligible; the projected sample size is 254. Participants are randomly assigned to a cilostazol or aspirin group at a 1:1 ratio. Cilostazol slow release 200 mg or aspirin 100 mg are taken once daily for 2 years. The primary outcome measure is the change in WMC volume on MRI from baseline to 104 weeks. Secondary imaging outcomes include changes in the number of lacunes and cerebral microbleeds, fractional anisotropy and mean diffusivity on diffusion tensor imaging, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability.CONCLUSIONS: CHALLENGE will provide evidence to support the selection of long-term antiplatelet therapy in CSVD.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01932203

A Comparative Evaluation of the KDSQ-C, AD8, and SMCQ as a Cognitive Screening Test to Be Used in National Medical Check-ups in Korea

BACKGROUND: Korea has a periodic general health check-up program that uses the Korean Dementia Screening Questionnaire-Cognition (KDSQ-C) as a cognitive dysfunction screening tool. The Alzheimer Disease 8 (AD8) and Subjective Memory Complaints Questionnaire (SMCQ) are also used in clinical practice. We compared the diagnostic ability of these screening questionnaires for cognitive impairment when completed by participants and their caregivers. Hence, we aimed to evaluate whether the SMCQ or AD8 is superior to the KDSQ-C and can be used as its replacement. METHODS: A total of 420 participants over 65 years and their informants were recruited from 11 hospitals for this study. The patients were grouped into normal cognition, mild cognitive impairment, and dementia subgroups. The KDSQ-C, AD8, and SMCQ were completed separately by participants and their informants. RESULTS: A receiver operating characteristic analysis of questionnaire scores completed by participants showed that the areas under the curve (AUCs) for the KDSQ-C, AD8, and SMCQ for diagnosing dementia were 0.75, 0.8, and 0.73, respectively. Regarding informant-completed questionnaires, the AD8 (AUC of 0.93), KDSQ-C (AUC of 0.92), and SMCQ (AUC of 0.92) showed good discriminability for dementia, with no differences in discriminability between the questionnaires. CONCLUSION: When an informant-report is possible, we recommend that the KDSQ-C continues to be used in national medical check-ups as its discriminability for dementia is not different from that of the AD8 or SMCQ. Moreover, consistent data collection using the same questionnaire is important. When an informant is not available, either the KDSQ-C or AD8 may be used. However, in the cases of patient-reports, discriminability is lower than that for informant-completed questionnaires.

Reversible Delayed Hypoxic Leukoencephalopathy from Respiration Failure during Sleep

No abstract available.

Age-Specific Cutoff Scores on a T1-Weighted Axial Medial Temporal-Lobe Atrophy Visual Rating Scale in Alzheimer's Disease Using Clinical Research Center for Dementia of South Korea Data

BACKGROUND AND PURPOSE: Visual assessment of medial temporal-lobe atrophy (MTA) has been quick, reliable, and easy to apply in routine clinical practice. However, one of the limitations in visual assessments of MTA is the lack of widely accepted age-adjusted norms and cutoff scores for MTA for a diagnosis of Alzheimer's disease (AD). This study aimed to determine the optimal cutoff score on a T1-weighted axial MTA Visual Rating Scale (VRS) for differentiating patients with AD from cognitively normal elderly people. METHODS: The 3,430 recruited subjects comprising 1,427 with no cognitive impairment (NC) and 2003 AD patients were divided into age ranges of 50–59, 60–69, 70–79, and 80–89 years. Of these, 446 participants (218 in the NC group and 228 in the AD group) were chosen by random sampling for inclusion in this study. Each decade age group included 57 individuals, with the exception of 47 subjects being included in the 80- to 89-year NC group. The scores on the T1-weighted axial MTA VRS were graded by two neurologists. The cutoff values were evaluated from the area under the receiver operating characteristic curve. RESULTS: The optimal axial MTA VRS cutoff score from discriminating AD from NC increased with age: it was ≥as ≥1, ≥2, and ≥3 in subjects aged 50–59, 60–69, 70–79, and 80–89 years, respectively (all p < 0.001). CONCLUSIONS: These results show that the optimal cutoff score on the axial MTA VRS for diagnosing of AD differed according to the decade age group. This information could be of practical usefulness in the clinical setting.

Sleep Related Problems as a Nonmotor Symptom of Dentatorubropallidoluysian Atrophy

Dentatorubropallidoluysian atrophy (DRPLA) is a neurodegenerative disease caused by an expansion of a cytosine-adenine-guanine (CAG) repeat encoding a polyglutamine tract in the atrophin-1 protein. Unlike other CAG repeat diseases, sleep related problems have not been reported in patients with DRPLA. There was a 65-year-old man and his family with DRPLA. They suffered from seizure, gait disturbance, and cognitive decline. The patients commonly showed dream enacting sleep disorder, insomnia. The results from overnight polysomnography showed rapid eye movement (REM) without atonia in patients with DRPLA. The man died 2 years after diagnosis and was subjected for brain autopsy. We report REM sleep behavior disorders in patients with DRPLA confirmed with polysomnography with pathological description of the patient.

A Case Report of Occipital Lobe Epilepsy and Related Optical Coherence Tomography Findings

PURPOSE: In the present case report, visual pathway damage confirmed by retinal ganglion cell layer (GCL) damage on optical coherence tomography (OCT) in occipital lobe epilepsy was described. CASE SUMMARY: A 25-year-old female with idiopathic generalized epilepsy developed visual blurring followed by a generalized seizure. On brain magnetic resonance imaging (MRI), very subtle changes of the cortex in the left parietooccipital lobe were observed. Two days after the attack, even after the disappearance of epileptiform wave on electroencephalogram (EEG), visual acuity in both eyes was 0.5 and a perimetry revealed nearly complete visual defect in both eyes. OCT showed severe thinning of GCL and mild thinning of retinal nerve fiber layer (RNFL). No additional seizure attack occurred thereafter. One month after the attack, her visual acuity was recovered to 1.0 in both eyes and her left visual hemifield defect was recovered. However, even 6 months after the attack, her right visual hemifield defect and GCL damage persisted in both eyes. CONCLUSIONS: We reported a case in which the visual pathway damage caused by occipital lobe epilepsy was identified using OCT, despite very subtle changes in brain imaging. This case indicated GCL thinning is an objective and prognostic index for the irreversible visual field defect in occipital lobe epilepsy.

The Effect of Rivastigmine Transdermal Patch on Sleep Apnea in Patients with Probable Alzheimer's Disease

BACKGROUND AND PURPOSE: This study was designed to evaluate the effect on sleep of rivastigmine transdermal patch in patients with probable Alzheimer's disease (AD). METHODS: Patients with probable AD underwent a sleep questionnaire, overnight polysomnography and neuropsychological tests before and after rivastigmine transdermal patch treatment. We analyzed the data from enrolled patients with AD. RESULTS: Fourteen patients with probable AD were finally enrolled in this study. The respiratory disturbance index after the rivastigmine patch treatment was improved in patients with probable AD and sleep breathing disorder, compared with that of before treatment (p<0.05). CONCLUSIONS: Rivastigmine transdermal patch application are expected to improve the symptoms of sleep disordered breathing in patients with probable AD. Further placebo controlled studies are needed to confirm these results.

Urachal Sinus Presenting with Periumbilicus Abscess / 대한소화기학회지

No abstract available.

Factors Influencing Skin Tolerability to the Rivastigmine Patch in Patients with Alzheimer's Disease

BACKGROUND AND PURPOSE: The one-day rivastigmine patch is reportedly well tolerated and has minimal side effects. However, Asian patients show more side effects than those in Western countries. We evaluated tolerability of the rivastigmine patch in South Korean patients with Alzheimer's disease (AD) and the specific factors affecting adverse events of the skin. METHODS: A 6-month, open labeled, multi-centered, observational study was carried out in 440 patients with probable AD from July 2009 to September 2010 (NCT01312363). RESULTS: A total of 25.9% of the patients experienced adverse skin events at the rivastigmine patch application site and 17.0% discontinued treatment due to adverse events at the skin application site. The most common adverse events were itching and erythema. Patients with an allergic history and users of electric heating appliances reported skin discomfort. Older age was associated with discontinuing treatment. CONCLUSION: These results suggest that the rivastigmine patch induced some adverse skin events and may contribute to understanding and improving skin tolerability to the rivastigmine patch.

Reversible Amygdala and Parahippocampal Lesions of Brain 18Fluorodeoxy Glucose-Positron Emission Tomography in Neuropsychiatric Systemic Lupus Erythematosus

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that is a significant source of morbidity and mortality when it manifests in the central nervous system. The early detection and treatment of neuropsychiatric SLE (NPSLE) is very important, but a confirmative diagnostic tool has yet to be developed. CASE REPORT: We report here a case of neuropsychiatric manifestations in a patient that were associated with SLE, and evidence of reversal of bilateral amygdala and parahippocampal lesions in the brain revealed by 18fluorodeoxy glucose-positron emission tomography. CONCLUSIONS: We are suggestive of 18fluorodeoxy glucose-positron emission tomography appear to be more sensitive in detecting subtle brain changes in NPSLE.

Vivid Dreaming after Acetyl-L-Carnitine Administration: A Report of Two Cases

Acetyl-L-carnitine (ALC), an acetylated form of L-carnitine, is able to influence the activity of cholinergic neurons, cell membrane stabilization and enhancing mitochondrial function. A 52-year-old woman was referred to neurology clinic for memory impairment within 1 year. She was administered ALC as dose of 1,500 mg per day for improving memory decline. After 14 days from administrating ALC, she complained vivid dreams at every night. Vivid dream was disappeared after ceasing ALC. Another patient, a 72-year-old man, visited neurology clinic for cognitive decline for 2 years. After 20 days from administering ALC with dose of 1,500 mg per day, he also suffered from vivid dreams at every night. His previous stable sleep was also restored after ceasing ALC. ALC supplementation may present vivid dreams as a side effect. Possibility of vivid dream as a side effect should be considered during the management with oral ALC.

The Effect of Group Musical Therapy on Depression and Activities on Daily Living in Patients with Cognitive Decline

BACKGROUND: Beside pharmacological treatment, non-pharmacological interventions are a great deal of interest resides on ways that allow modulation of brain plasticity in the elderly. Music therapy is a potential non-pharmacological treatment for the behavioral and psychological symptoms of dementia, but a few studies reported it to be helpful. The aim of this study was to evaluate the effect of structured musical intervention therapy in patient with cognitive decline. METHODS: The subjects of the study were a total of fifty elderly with cognitive decline (K-MMSE: 21+/-3.99, CDR: 0.80+/-0.38). The musical therapy was applied to the group twice a week, fifty minutes per session for eight weeks. The data were analyzed by using chi-square and paired t-test before and after musical intervention. RESULTS: The study showed a significant reduction in depression and anxiety after musical therapy measured with short form-GDS and BDI (p<0.001). Activities daily living (ADL) markedly improved after the all session of musical interventions (p<0.001). CONCLUSION: Group music therapy is a safe and effective method for treating depression and anxiety, and also improving ADL in patients with cognitive decline.

Delayed presentation of aggravation of thyrotoxicosis after radioactive iodine therapy at Graves disease / 영남의대학술지

Radioactive iodine (RAI) therapy is widely used for the treatment of Graves disease. After RAI therapy, 44% become hypothyroid and up to 28% remain hyperthyroid. The development of thyrotoxicosis after RAI therapy is believed to be mediated by 2 different mechanisms: a transient increased release of thyroid hormone due to radiation thyroiditis and the rare development of Graves disease due to the formation of antibodies to the thyroid-associated antigens released from the damaged follicular cells. A 55-year-old woman was hospitalized with severe headache, weight loss, and palpitation. She received a dose of 7 mCi of RAI (I-131) about 6 weeks earlier. Thyroid function test showed 7.98 ng/dL free T4, >8 ng/mL T3, <0.08 microIU/L thyroid stimulating hormone, and high titer thyroid stimulating immunoglobulin (TSI) (85.8 IU/L). She improved with propylthiouracil, propranolol, and steroid treatment. The TSI, however, was persistently elevated for 11 months.

Portal-Splenic-Mesenteric Venous Thrombosis in a Patients with Protein S Deficiency due to Novel PROS1 Gene Mutation / 대한소화기학회지

Protein S (PS), a vitamin K-dependent glycoprotein, performs an important role in the anticoagulation cascade as a cofactor of protein C. Because of the presence of a pseudogene and two different forms of PS in the plasma, protein S deficiency (PSD) is one of the most difficult thrombophilias to study and a rare blood disorder associated with an increased risk of thrombosis. We describe a unusual case of previously healthy 37-year-old man diagnosed with portal-splenic-mesenteric vein thrombosis secondary to PSD. The patient was admitted to the hospital due to continuous nonspecific abdominal pain and nausea. Abdominal computed tomography revealed acute venous thrombosis from inferior mesenteric vein to left portal vein via splenic vein, and laboratory test revealed decreased PS antigen level and PS functional activity. Conventional polymerase chain reaction and direct DNA sequencing analysis of the PROS1 gene demonstrated duplication of the 166th base in exon 2 resulting in frame-shift mutation (p.Arg56Lysfs*10) which is the first description of the new PROS1 gene mutation to our knowledge. Results from other studies suggest that the inherited PSD due to a PROS1 gene mutation may cause venous thrombosis in a healthy young man without any known predisposing factor.

Response: The Association between Serum Endogenous Secretory Receptor for Advanced Glycation End Products and Vertebral Fractures in Type 2 Diabetes (Endocrinol Metab 2012;27:289-94, Cheol Ho Lee et al.)

No abstract available.

Cerebral Achromatopsia After Posterior Cerebral Artery Infarction

Cerebral achromatopsia, which refers to a loss of color vision, is a rare complication of posterior circulation stroke. We report two patients who presented with achromatopsia and dyschromatopsia (incomplete form of achromatopsia) respectively after acute posterior cerebral artery infarction. Lingual and fusiform gyri within the occipito-temporal area are known to be responsible for color perception.

Recurrence of Coronary-Subclavian Steal Syndrome After Successful Angioplasty of Malfunctioning Arteriovenous Fistula

We report a case of coronary-subclavian steal syndrome, which had been masked by a malfunctioning hemodialysis access vessel and then reappeared after a successful angioplasty of multiple stenoses in the arteriovenous fistula of the left arm in a 61-year-old man. This case suggests that coronary-subclavian steal syndrome should be considered before a coronary artery bypass grafting surgery using internal mammary artery conduit is done, especially when hemodialysis using the left arm vessels is expected.