Journal of clinical neurology (Seoul, Korea), 2018
Visual assessment of medial temporal-lobe atrophy (MTA) has been quick, reliable, and easy to app... more 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. 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 n...
While dementia is mainly characterized by cognitive alterations, behavioral and psychological sym... more While dementia is mainly characterized by cognitive alterations, behavioral and psychological symptoms are very common, increasing the risk of poor outcome. The most common alterations reported in dementia patients are apathy and decreased sexual interest. Nevertheless, inappropriate sexual behavior (ISB) has also frequently been described in many cases of dementia, and it has increasingly been recognized as an important symptom. ISB is more frequent among institutionalized patients and those with greater cognitive impairment. 3 Given the profoundly disruptive nature of ISB, especially to caregivers and other residents in nursing facilities, there have been efforts in the appropriate management of ISB. The general consensus has been that non-pharmacological interventions, including an environmental or behavioral approach, should be prioritized due to safety and ethical issues. Only when such efforts are not responsive, a pharmacological approach should be considered. However, there has not been any randomized controlled trial regarding the effects of medications on ISB, with only case reports to date. Hormonal agents are one option for ISB. A number of case reports have shown that they achieved a significant reduction in ISB patients sexually acting out post-administration of hormonal agents that lowered testosterone production. Cyproterone acetate (CPA) is a synthetic progestin and anti-androgen that works by inhibiting the interaction between endogenous androgens and androgen receptors, as well as by reducing the biosynthesis of androgens. In the present study, we investigated whether CPA is an effective and safe pharmacological approach to reduce moderate-to-severe ISB in older patients with dementia. The study protocol was approved by the institutional review board of Seoul National University Bundang Hospital and conforms to the provisions of the Declaration of Helsinki. A consecutive series of 10 older male patients with dementia, who visited the Department of Neurology of Seoul National University Bundang Hospital between April 2014 and June 2017, were treated with CPA. They showed moderate-to-severe ISB, which corresponded to stage 2 or higher on the overt behavior scale of inappropriate sexual behavior category. In these patients, a non-pharmacological approach was used, without much success, before administration of CPA. Table 1 shows the patient characteristics, description of ISB and dosage of CPA prescribed. CPA effectively reduced ISB in all patients. Five patients responded to 25 mg of CPA twice a day, whereas four patients responded to 50 mg of CPA twice a day. One patient with Alzheimer’s disease responded to 75 mg of CPA twice a day; but the medication was stopped as a result of depression and fatigue, which disappeared soon after discontinuation of CPA. There were no laboratory abnormalities or other relevant side-effects associated with CPA in all patients. The present findings show that CPA is an effective pharmacological strategy for managing ISB. A previous case report suggested CPA as a potent agent for ISB. In their report, 10 mg of CPA was used with beneficial effects in two men with dementia-related ISB after unsuccessful attempts with antipsychotic or sedative medication. However, another case report described unsuccessful CPA treatment in a 70-year-old dementia patient with a dosage of 50 mg twice a day; this patient developed adverse side-effects – impairment of mobility – that recovered after discontinuation. The possible side-effects of CPA include fatigue, gynecomastia, weight gain, dry skin, hair loss, depressive mood, sleepiness, hepatocellular damage, and rarely, thromboembolism. Although the use of CPA in the geriatric population might be associated with such disadvantages, there have not been any reported cases of major side-effects in dementia patients for the purpose of behavioral management. To date, CPA has already been used extensively in older male patients for the treatment of prostate cancer, and most side-effects have been shown to emerge with a dosage of >300 mg/day. CPA can also be used to control aggression (excluding hypersexuality-related behaviors) in dementia. There has been a case report describing the successful management of aggression in a patient with Alzheimer’s disease, who initially failed other medications. A randomized double-blind trial that included 27 participants with Alzheimer’s disease comparing CPA with haloperidol has also showed that CPA might be more effective in controlling aggression and was associated with fewer side-effects. CPA can be an effective alternative to antipsychotic drugs, especially in patients with dementia with Lewy bodies, as introducing antipsychotic drugs can increase the risk of worsening parkinsonian symptoms. In the present pilot study, we showed that CPA can be an effective treatment method for moderate-to-
Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acety... more Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer's disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs. Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study. Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 13...
Journal of the neurological sciences, Jan 15, 2016
We designed this study to extensively compare the neuropsychological profiles of Alzheimer's ... more We designed this study to extensively compare the neuropsychological profiles of Alzheimer's disease (AD) and mixed dementia (MD) in a large multicenter cohort of patients. Specifically, we performed subgroup analyses to examine group differences associated with dementia severity. A total of 1021 AD patients and 577 MD patients were included from the Clinical Research Center for Dementia of South Korea (CREDOS) Study. All patients underwent comprehensive neuropsychological and functional ratings, as well as complete physical and neurological examinations. To avoid floor confounds, only patients with Clinical Dementia Rating (CDR) scores of 0.5-2.0 were included. Overall, MD patients showed worse performance in frontal/executive function than those with AD. Stratification by dementia severity revealed a significant difference in global cognitive function scores between AD and MD patients only in the low severity groups (CDR 0.5). Also, MD patients showed worse performance in fron...
Recently, a Korean research group suggested a consensus protocol, based on the Alzheimer's Di... more Recently, a Korean research group suggested a consensus protocol, based on the Alzheimer's Disease Neuroimaging Initiative study protocol but with modifications for minimizing the confounding factors, for the evaluation of cerebrospinal fluid (CSF) biomarkers. Here, we analyzed fluid and imaging biomarkers of Alzheimer's disease (AD) in Korean population. We used the updated protocol to propose a more accurate CSF biomarker value for the diagnosis of AD. Twenty-seven patients with AD and 30 cognitively normal controls (NC) were enrolled. CSF was collected from 55 subjects (patients with AD = 26, NC = 29) following the Korea consensus protocol. CSF biomarkers were measured using the INNO-BIA AlzBio3 immunoassay, and Pittsburgh compound B (PIB) positron emission tomography (PET) scans were also performed. The cutoff values of CSF amyloid beta 1-42 (Aβ42), total tau (t-Tau), and phosphorylated tau (p-Tau) proteins were 357.1 pg/ml, 83.35 pg/ml, and 38.00 pg/ml, respectively. Th...
The aims of this study were to investigate concrete and abstract word definition ability (1) betw... more The aims of this study were to investigate concrete and abstract word definition ability (1) between patients with amnestic mild cognitive impairment (aMCI) and normal adults and (2) between the aMCI subtypes (i.e., amnestic single-domain MCI and amnestic multidomain MCI; asMCI and amMCI) and normal controls. The 68 patients with aMCI (29 asMCI and 39 amMCI) and 93 age- and education-matched normal adults performed word definition tasks composed of five concrete (e.g., train) and five abstract nouns (e.g., jealousy). Task performances were analyzed on total score, number of core meanings, and number of supplementary meanings. The results were as follows. First, the aMCI patients scored significantly poorer than the normal controls in only abstract word definition. Second, both subtypes of aMCI performed worse than the controls in only abstract word definition. In conclusion, a definition task of abstract rather than concrete concepts may provide richer information to show semantic i...
Bacillus cereus meningitis can show unusual presentation and very rapid progression associated wi... more Bacillus cereus meningitis can show unusual presentation and very rapid progression associated with high mortality and unusual MRI findings. We report a 77-year-old man with fever and altered mentality after epidural neuroplasty for chronic lumbar spinal pain. Symptoms rapidly progressed over the 12 hours following surgery. He was diagnosed with meningoencephalitis by Bacillus cereus confirmed by CSF culture and DNA sequencing. He improved with antibiotics slowly although his mental state did not completely revert to his prior level. This case demonstrates the rapid and fulminant clinical picture produced by Bacillus cereus associated with neuroplasty. It also shows peculiar frontal white matter changes with hydrocephalus on MRI
We report the clinical, neuropsychological, and neuroimaging findings of two patients of diffuse ... more We report the clinical, neuropsychological, and neuroimaging findings of two patients of diffuse encephalopathy associated with the use of metronidazole. Both patients showed characteristic abnormalities on magnetic resonance imaging (MRI) with diffusion weighted imaging (DWI) and recovered incompletely after the discontinuation of metronidazole. We also suggest that MRI with DWI may be useful in the diagnosis of metronidazole-induced encephalopathy, and that they have a role in the prediction of prognosis.
Journal of Geriatric Psychiatry and Neurology, 2011
We investigated the associations of periventricular white matter hyperintensities (PWMHs) and dee... more We investigated the associations of periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs) with cognition, activities of daily living (ADLs), and neuropsychiatric symptoms in dementia. This was a hospital-based MRI300 study. We recruited patients newly diagnosed with mild-to-moderate dementia caused either by Alzheimer's disease or subcortical ischemic vascular dementia from 13 dementia clinics at university or general hospitals in South Korea. We enrolled 289 patients aged over 50 from August 2007 to March 2008. We compared cognition, ADLs, and neuropsychiatric symptoms among 3 groups according to the severities of PWMHs and DWMHs, respectively, by adjusting for age, vascular risk factors, and level of other WMHs. A higher severity of PWMHs was related to lower cognitive function and severer neuropsychiatric symptoms, whereas basic ADLs were associated with DWMH. Both PWMHs and DWMHs exhibited different associations with cognition, neuropsychiatric symptoms, and daily activities.
Journal of clinical neurology (Seoul, Korea), 2018
Visual assessment of medial temporal-lobe atrophy (MTA) has been quick, reliable, and easy to app... more 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. 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 n...
While dementia is mainly characterized by cognitive alterations, behavioral and psychological sym... more While dementia is mainly characterized by cognitive alterations, behavioral and psychological symptoms are very common, increasing the risk of poor outcome. The most common alterations reported in dementia patients are apathy and decreased sexual interest. Nevertheless, inappropriate sexual behavior (ISB) has also frequently been described in many cases of dementia, and it has increasingly been recognized as an important symptom. ISB is more frequent among institutionalized patients and those with greater cognitive impairment. 3 Given the profoundly disruptive nature of ISB, especially to caregivers and other residents in nursing facilities, there have been efforts in the appropriate management of ISB. The general consensus has been that non-pharmacological interventions, including an environmental or behavioral approach, should be prioritized due to safety and ethical issues. Only when such efforts are not responsive, a pharmacological approach should be considered. However, there has not been any randomized controlled trial regarding the effects of medications on ISB, with only case reports to date. Hormonal agents are one option for ISB. A number of case reports have shown that they achieved a significant reduction in ISB patients sexually acting out post-administration of hormonal agents that lowered testosterone production. Cyproterone acetate (CPA) is a synthetic progestin and anti-androgen that works by inhibiting the interaction between endogenous androgens and androgen receptors, as well as by reducing the biosynthesis of androgens. In the present study, we investigated whether CPA is an effective and safe pharmacological approach to reduce moderate-to-severe ISB in older patients with dementia. The study protocol was approved by the institutional review board of Seoul National University Bundang Hospital and conforms to the provisions of the Declaration of Helsinki. A consecutive series of 10 older male patients with dementia, who visited the Department of Neurology of Seoul National University Bundang Hospital between April 2014 and June 2017, were treated with CPA. They showed moderate-to-severe ISB, which corresponded to stage 2 or higher on the overt behavior scale of inappropriate sexual behavior category. In these patients, a non-pharmacological approach was used, without much success, before administration of CPA. Table 1 shows the patient characteristics, description of ISB and dosage of CPA prescribed. CPA effectively reduced ISB in all patients. Five patients responded to 25 mg of CPA twice a day, whereas four patients responded to 50 mg of CPA twice a day. One patient with Alzheimer’s disease responded to 75 mg of CPA twice a day; but the medication was stopped as a result of depression and fatigue, which disappeared soon after discontinuation of CPA. There were no laboratory abnormalities or other relevant side-effects associated with CPA in all patients. The present findings show that CPA is an effective pharmacological strategy for managing ISB. A previous case report suggested CPA as a potent agent for ISB. In their report, 10 mg of CPA was used with beneficial effects in two men with dementia-related ISB after unsuccessful attempts with antipsychotic or sedative medication. However, another case report described unsuccessful CPA treatment in a 70-year-old dementia patient with a dosage of 50 mg twice a day; this patient developed adverse side-effects – impairment of mobility – that recovered after discontinuation. The possible side-effects of CPA include fatigue, gynecomastia, weight gain, dry skin, hair loss, depressive mood, sleepiness, hepatocellular damage, and rarely, thromboembolism. Although the use of CPA in the geriatric population might be associated with such disadvantages, there have not been any reported cases of major side-effects in dementia patients for the purpose of behavioral management. To date, CPA has already been used extensively in older male patients for the treatment of prostate cancer, and most side-effects have been shown to emerge with a dosage of >300 mg/day. CPA can also be used to control aggression (excluding hypersexuality-related behaviors) in dementia. There has been a case report describing the successful management of aggression in a patient with Alzheimer’s disease, who initially failed other medications. A randomized double-blind trial that included 27 participants with Alzheimer’s disease comparing CPA with haloperidol has also showed that CPA might be more effective in controlling aggression and was associated with fewer side-effects. CPA can be an effective alternative to antipsychotic drugs, especially in patients with dementia with Lewy bodies, as introducing antipsychotic drugs can increase the risk of worsening parkinsonian symptoms. In the present pilot study, we showed that CPA can be an effective treatment method for moderate-to-
Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acety... more Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer's disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs. Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study. Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 13...
Journal of the neurological sciences, Jan 15, 2016
We designed this study to extensively compare the neuropsychological profiles of Alzheimer's ... more We designed this study to extensively compare the neuropsychological profiles of Alzheimer's disease (AD) and mixed dementia (MD) in a large multicenter cohort of patients. Specifically, we performed subgroup analyses to examine group differences associated with dementia severity. A total of 1021 AD patients and 577 MD patients were included from the Clinical Research Center for Dementia of South Korea (CREDOS) Study. All patients underwent comprehensive neuropsychological and functional ratings, as well as complete physical and neurological examinations. To avoid floor confounds, only patients with Clinical Dementia Rating (CDR) scores of 0.5-2.0 were included. Overall, MD patients showed worse performance in frontal/executive function than those with AD. Stratification by dementia severity revealed a significant difference in global cognitive function scores between AD and MD patients only in the low severity groups (CDR 0.5). Also, MD patients showed worse performance in fron...
Recently, a Korean research group suggested a consensus protocol, based on the Alzheimer's Di... more Recently, a Korean research group suggested a consensus protocol, based on the Alzheimer's Disease Neuroimaging Initiative study protocol but with modifications for minimizing the confounding factors, for the evaluation of cerebrospinal fluid (CSF) biomarkers. Here, we analyzed fluid and imaging biomarkers of Alzheimer's disease (AD) in Korean population. We used the updated protocol to propose a more accurate CSF biomarker value for the diagnosis of AD. Twenty-seven patients with AD and 30 cognitively normal controls (NC) were enrolled. CSF was collected from 55 subjects (patients with AD = 26, NC = 29) following the Korea consensus protocol. CSF biomarkers were measured using the INNO-BIA AlzBio3 immunoassay, and Pittsburgh compound B (PIB) positron emission tomography (PET) scans were also performed. The cutoff values of CSF amyloid beta 1-42 (Aβ42), total tau (t-Tau), and phosphorylated tau (p-Tau) proteins were 357.1 pg/ml, 83.35 pg/ml, and 38.00 pg/ml, respectively. Th...
The aims of this study were to investigate concrete and abstract word definition ability (1) betw... more The aims of this study were to investigate concrete and abstract word definition ability (1) between patients with amnestic mild cognitive impairment (aMCI) and normal adults and (2) between the aMCI subtypes (i.e., amnestic single-domain MCI and amnestic multidomain MCI; asMCI and amMCI) and normal controls. The 68 patients with aMCI (29 asMCI and 39 amMCI) and 93 age- and education-matched normal adults performed word definition tasks composed of five concrete (e.g., train) and five abstract nouns (e.g., jealousy). Task performances were analyzed on total score, number of core meanings, and number of supplementary meanings. The results were as follows. First, the aMCI patients scored significantly poorer than the normal controls in only abstract word definition. Second, both subtypes of aMCI performed worse than the controls in only abstract word definition. In conclusion, a definition task of abstract rather than concrete concepts may provide richer information to show semantic i...
Bacillus cereus meningitis can show unusual presentation and very rapid progression associated wi... more Bacillus cereus meningitis can show unusual presentation and very rapid progression associated with high mortality and unusual MRI findings. We report a 77-year-old man with fever and altered mentality after epidural neuroplasty for chronic lumbar spinal pain. Symptoms rapidly progressed over the 12 hours following surgery. He was diagnosed with meningoencephalitis by Bacillus cereus confirmed by CSF culture and DNA sequencing. He improved with antibiotics slowly although his mental state did not completely revert to his prior level. This case demonstrates the rapid and fulminant clinical picture produced by Bacillus cereus associated with neuroplasty. It also shows peculiar frontal white matter changes with hydrocephalus on MRI
We report the clinical, neuropsychological, and neuroimaging findings of two patients of diffuse ... more We report the clinical, neuropsychological, and neuroimaging findings of two patients of diffuse encephalopathy associated with the use of metronidazole. Both patients showed characteristic abnormalities on magnetic resonance imaging (MRI) with diffusion weighted imaging (DWI) and recovered incompletely after the discontinuation of metronidazole. We also suggest that MRI with DWI may be useful in the diagnosis of metronidazole-induced encephalopathy, and that they have a role in the prediction of prognosis.
Journal of Geriatric Psychiatry and Neurology, 2011
We investigated the associations of periventricular white matter hyperintensities (PWMHs) and dee... more We investigated the associations of periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs) with cognition, activities of daily living (ADLs), and neuropsychiatric symptoms in dementia. This was a hospital-based MRI300 study. We recruited patients newly diagnosed with mild-to-moderate dementia caused either by Alzheimer's disease or subcortical ischemic vascular dementia from 13 dementia clinics at university or general hospitals in South Korea. We enrolled 289 patients aged over 50 from August 2007 to March 2008. We compared cognition, ADLs, and neuropsychiatric symptoms among 3 groups according to the severities of PWMHs and DWMHs, respectively, by adjusting for age, vascular risk factors, and level of other WMHs. A higher severity of PWMHs was related to lower cognitive function and severer neuropsychiatric symptoms, whereas basic ADLs were associated with DWMH. Both PWMHs and DWMHs exhibited different associations with cognition, neuropsychiatric symptoms, and daily activities.
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Papers by Sangyun Kim