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no abstract available.
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Recently, aducanumab, a beta amyloid targeted immunotherapy, has been approved by the US Food and Drug Administration for the treatment of Alzheimer’s dementia (AD). Although many questions need to be answered, this approval provides a promising hope for the development of AD drugs that could be supported by new biomarkers such as blood-based ones and composite neuropsychological tests that can confirm pathologic changes in early stages of AD. It is important to elucidate the complexity of AD which is known to be associated with other factors such as vascular etiologies and neuro-inflammation. Through the second international conference of the Korean Dementia Association (KDA), researchers from all over the world have participated in the exchange of opinions with KDA members on the most up-to-date topics. The Academic Committee of the KDA summarizes lectures to provide the depth of the conference as well as discussions. This will be an important milestone to widen the latest knowledge in the research of AD’s diagnosis, therapeutics, pathogenesis that can lead to the establishment of future directions.
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Because of repeated failures of clinical trials, the concept of Alzheimer's disease (AD) has been changing rapidly in recent years. As suggested by the National Institute on Aging and the Alzheimer's Association Research Framework, the diagnosis and classification of AD is now based on biomarkers rather than on symptoms, allowing more accurate identification of proper candidates for clinical trials by pathogenesis and disease stage. Recent development in neuroimaging has provided a way to reveal the complex dynamics of amyloid and tau in the brain in vivo, and studies of blood biomarkers are taking another leap forward in diagnosis and treatment of AD. In the field of basic and translational research, the development of animal models and a deeper understanding of the role of neuroinflammation are taking a step closer to clarifying the pathogenesis of AD. Development of big data and the Internet of Things is also incorporating dementia care and research into other aspects. Largescale genetic research has identified genetic abnormalities that can provide a foundation for precision medicine along with the aforementioned digital technologies. Through the first international conference of the Korean Dementia Association, experts from all over the world gathered to exchange opinions with association members on these topics. The Academic Committee of the Korean Dementia Association briefly summarizes the contents of the lectures to convey the depth of the conference and discussions. This will be an important milestone in understanding the latest trends in AD's pathogenesis, diagnostic and therapeutic research and in establishing a future direction.
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Background@#Computerized versions of cognitive screening test could have advantages over pencil-and-paper versions by eliminating rater-dependent factors and saving the time required to score the tests and report the results. We developed a computerized cognitive screening test (Inbrain Cognitive Screening Test [Inbrain CST]) that takes about 30 minutes to administer on a touchscreen computer and is composed of neuropsychological tests already shown to be sensitive in detecting early cognitive decline in Alzheimer's disease (AD). The aims of this study were to 1) introduce normative data for Inbrain CST, 2) verify its reliability and validity, 3) assess clinical usefulness, and 4) identify neuroanatomical correlates of Inbrain CST. @*Methods@#The Inbrain CST runs on the Microsoft Windows 10 operating system and comprises 7 subtests that encompass 5 cognitive domains: attention, language, visuospatial, memory, and executive functions. First, we recruited 480 cognitively normal elderly people (age 50–90) from communities nationwide to establish normative data for Inbrain CST.Second, we enrolled 97 patients from our dementia clinic (26 with subjective cognitive decline [SCD], 42 with amnestic mild cognitive impairment [aMCI], and 29 with dementia due to AD) and investigated sensitivity and specificity of Inbrain CST for discriminating cognitively impaired patients from those with SCD using receiver operating characteristic (ROC) curve analyses. Third, we compared the Inbrain CST scores with those from another neuropsychological test battery to obtain concurrent validity and assessed test–retest reliability. Finally, magnetic resonance imaging (MRI)-based cortical thickness analyses were performed to provide anatomical substrates for performances on the Inbrain CST. @*Results@#First, in the normative sample, the total score on the Inbrain CST was significantly affected by age, years of education, and gender. Second, Inbrain CST scores among the three patient groups decreased in the order of SCD, aMCI, and AD dementia, and the ROC curve analysis revealed that Inbrain CST had good discriminative power for differentiating cognitively impaired patients from those with SCD. Third, the Inbrain CST subtests had high concurrent validity and test–retest reliability. Finally, in the cortical thickness analysis, each cognitive domain score and the total score of Inbrain CST showed distinct patterns of anatomical correlates that fit into the previously known brain–behavior relationship. @*Conclusion@#Inbrain CST had good validity, reliability, and clinical usefulness in detecting cognitive impairment in the elderly. Furthermore, it showed neuroanatomical validity through MRI cortical thinning patterns. These results suggest that Inbrain CST is a useful cognitive screening tool with efficiency and validity to detect mild impairments in cognition in clinical settings.
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Objectives@#To investigate the relationship between subjective sleep quality and cognitive function in patients with subjective memory impairment (SMI), a self-perceived cognitive decline without objective cognitive impairment, and amnestic mild cognitive impairment (aMCI). @*Methods@#We enrolled 246 patients with memory impairment (126 with SMI and 120 with aMCI) who fulfilled the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K), a standardized battery of neuropsychological tests, and mood questionnaires. Based on the PSQI-K cutoff point of 5, patients were classified as good sleepers (GS) or poor sleepers (PS). @*Results@#There was no difference in the proportion of GS and PS between patients with SMI and aMCI [68 PS (54.0%) in SMI vs. 62 PS (51.7%) in aMCI, p>0.05]. Demographics did not differ between the SMI and aMCI groups. In both the SMI and aMCI groups, PS had worse sleep-wake parameters, such as sleep latency, total sleep time, and sleep efficiency, than GS and reported worse performance in all PSQI-K subcomponents. Neuropsychological data were not different between GS and PS, except for the Stroop word test in patients with aMCI. Depressive scores were worse in PS than in GS in both the SMI and aMCI groups. @*Conclusions@#We observed that cognitive function was not significantly different between GS and PS in both the SMI and aMCI groups, except in the Stroop word test in the aMCI group, while PS had more depressive mood than GS in both groups. This suggests that subjective sleep quality may depend on mood disturbances in patients with mild cognitive impairment.
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Objectives@#To investigate the relationship between subjective sleep quality and cognitive function in patients with subjective memory impairment (SMI), a self-perceived cognitive decline without objective cognitive impairment, and amnestic mild cognitive impairment (aMCI). @*Methods@#We enrolled 246 patients with memory impairment (126 with SMI and 120 with aMCI) who fulfilled the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K), a standardized battery of neuropsychological tests, and mood questionnaires. Based on the PSQI-K cutoff point of 5, patients were classified as good sleepers (GS) or poor sleepers (PS). @*Results@#There was no difference in the proportion of GS and PS between patients with SMI and aMCI [68 PS (54.0%) in SMI vs. 62 PS (51.7%) in aMCI, p>0.05]. Demographics did not differ between the SMI and aMCI groups. In both the SMI and aMCI groups, PS had worse sleep-wake parameters, such as sleep latency, total sleep time, and sleep efficiency, than GS and reported worse performance in all PSQI-K subcomponents. Neuropsychological data were not different between GS and PS, except for the Stroop word test in patients with aMCI. Depressive scores were worse in PS than in GS in both the SMI and aMCI groups. @*Conclusions@#We observed that cognitive function was not significantly different between GS and PS in both the SMI and aMCI groups, except in the Stroop word test in the aMCI group, while PS had more depressive mood than GS in both groups. This suggests that subjective sleep quality may depend on mood disturbances in patients with mild cognitive impairment.
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BACKGROUND AND PURPOSE: In Alzheimer's continuum (a comprehensive of preclinical Alzheimer's disease [AD], mild cognitive impairment [MCI] due to AD, and AD dementia), cognitive dysfunctions are often related to cortical atrophy in specific brain regions. The purpose of this study was to investigate the association between anatomical pattern of cortical atrophy and specific neuropsychological deficits. METHODS: A total of 249 participants with Alzheimer's continuum (125 AD dementia, 103 MCI due to AD, and 21 preclinical AD) who were confirmed to be positive for amyloid deposits were collected from the memory disorder clinic in the department of neurology at Samsung Medical Center in Korea between September 2013 and March 2018. To analyze neuropsychological test-specific neural correlates representing the relationship between cortical atrophy measured by cortical thickness and performance in specific neuropsychological tests, a linear regression analysis was performed. Two neural correlates acquired by 2 different standardized scores in neuropsychological tests were also compared. RESULTS: Cortical atrophy in several specific brain regions was associated with most neuropsychological deficits, including digit span backward, naming, drawing-copying, verbal and visual recall, semantic fluency, phonemic fluency, and response inhibition. There were a few differences between 2 neural correlates obtained by different z-scores. CONCLUSIONS: The poor performance of most neuropsychological tests is closely related to cortical thinning in specific brain areas in Alzheimer's continuum. Therefore, the brain atrophy pattern in patients with Alzheimer's continuum can be predict by an accurate analysis of neuropsychological tests in clinical practice.
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Humans , Alzheimer Disease , Atrophy , Brain , Cognition , Dementia , Korea , Linear Models , Memory Disorders , Cognitive Dysfunction , Neuroanatomy , Neurology , Neuropsychological Tests , Plaque, Amyloid , SemanticsABSTRACT
BACKGROUND AND PURPOSE: Evaluating instrumental activities of daily living (IADL) is an important part of procedure to diagnose dementia. The Korean-Instrumental Activities of Daily Living (K-IADL) has been used extensively in Korea. However, its cut-off score has not been reformulated since 2002. The purpose of this study was to yield a new optimal cut-off score for the K-IADL and confirm the validity of this new cut-off score with various dementia groups. METHODS: We retrospectively collected a total of 2,347 patients' K-IADL data from 6 general hospitals in Korea. These patients had mild cognitive impairment (MCI) or dementia with various etiologies for cognitive impairment. We also recruited a normal control group (n=254) from the community. Korean-Mini Mental State Examination, Short version of the Geriatric Depression Scale, Clinical Dementia Rating, and Global Deterioration Scale were administered to all participants. Caregivers completed K-IADL and Barthel Index. RESULTS: K-IADL scores were significantly different among dementia subgroups, but not significantly different among MCI subgroups. Based on internal consistency, correlations with other scales, and factor analysis, K-IADL showed excellent reliability and validity. The new optimal cut-off score to diagnose dementia was 0.40, which gave a sensitivity of 0.901 and a specificity of 0.916. Positive predictive value for dementia using the new cut-off score was 94.2% for Alzheimer's disease, 100% for vascular dementia, and 84% for Parkinson's disease. CONCLUSIONS: Our results illustrate that the new K-IADL cut-off score of 0.40 is reliable and valid for screening impairments of daily functioning resulting from various etiologies.
Subject(s)
Humans , Activities of Daily Living , Alzheimer Disease , Caregivers , Cognition Disorders , Dementia , Dementia, Vascular , Depression , Hospitals, General , Korea , Mass Screening , Cognitive Dysfunction , Parkinson Disease , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Weights and MeasuresABSTRACT
Gerstmann's syndrome, assigned to a lesion of the dominant parietal lobe, is a neurological disorder characterized by acalculia, agraphia, right-left disorientation and finger agnosia. Some studies report that these symptoms are also shown in other brain lesions. We report two patients who presented with this tetrad of symptoms in initial assessment. Their Brain MRI images both showed lesion of left frontal lobe. Over time, these symptoms became better but some still remained in last assessment. Accordingly, we suggest that a left frontal lesion cause Gerstmann's syndrome.
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Humans , Agnosia , Agraphia , Brain , Dyscalculia , Frontal Lobe , Gerstmann Syndrome , Magnetic Resonance Imaging , Nervous System Diseases , Parietal LobeABSTRACT
PURPOSE: The purpose of this study was to know psychological characteristics of psychogenic non-epileptic seizure (PNES) patients by analyzing profiles of Minnesota Multiphasic Personality Inventory (MMPI). In addition, we tried to investigate whether there are differences of MMPI profiles, depending on the gender and age. METHODS: We included 65 patients with non-epileptic psychogenic seizures. Their diagnosis was based on clinical features, provocative test and confirmed by video-EEG monitoring. RESULTS: The results of MMPI analysis did not show any statistically significant differences of quantitative scoring on the main clinical scales. However, additional analysis indicated that patients with PNES had some characteristics of more somatic complaints and depressive mood. According to sex difference, the MMPI profiles of female group showed an increase in the depression scale (D-Pt), whereas those of male group revealed an increased in the somatisation (Hs-Hy). According to age difference, MMPI profiles of adolescent group had the characteristics of personality pattern with a tendency toward somatisation. MMPI profiles of adult group had more depressive tendency. This study suggests that profiles of MMPI, according to the gender and age, can have different characteristics. CONCLUSIONS: Clinical consideration of those factors may be helpful for improving the care of PNES patients.
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Adolescent , Adult , Female , Humans , Male , Depression , Epilepsy , MMPI , Seizures , Sex Characteristics , Weights and MeasuresABSTRACT
PURPOSE: The purpose of this study was to know psychological characteristics of psychogenic non-epileptic seizure (PNES) patients by analyzing profiles of Minnesota Multiphasic Personality Inventory (MMPI). In addition, we tried to investigate whether there are differences of MMPI profiles, depending on the gender and age.METHODS: We included 65 patients with non-epileptic psychogenic seizures. Their diagnosis was based on clinical features, provocative test and confirmed by video-EEG monitoring.RESULTS: The results of MMPI analysis did not show any statistically significant differences of quantitative scoring on the main clinical scales. However, additional analysis indicated that patients with PNES had some characteristics of more somatic complaints and depressive mood. According to sex difference, the MMPI profiles of female group showed an increase in the depression scale (D-Pt), whereas those of male group revealed an increased in the somatisation (Hs-Hy). According to age difference, MMPI profiles of adolescent group had the characteristics of personality pattern with a tendency toward somatisation. MMPI profiles of adult group had more depressive tendency. This study suggests that profiles of MMPI, according to the gender and age, can have different characteristics.CONCLUSIONS: Clinical consideration of those factors may be helpful for improving the care of PNES patients.
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Adolescent , Adult , Female , Humans , Male , Depression , Epilepsy , MMPI , Seizures , Sex Characteristics , Weights and MeasuresABSTRACT
BACKGROUND AND PURPOSE: The occurrence of PWD in neurodegenerative disease is very rare, and this is the first report of it being related to early-onset AD. We describe a patient with early-onset Alzheimer's disease (AD) who presented with pure word deafness (PWD). CASE REPORT: The patient had experienced PWD for 2 years, followed by other cognitive deficits suggestive of parietotemporal dysfunction. Brain imaging including 18FDG-PET and [11C] PIB-PET supported the diagnosis of AD. CONCLUSIONS: Our case highlights the clinical variability that characterizes early-onset AD.
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Humans , Alzheimer Disease , Aphasia, Primary Progressive , Deafness , Neurodegenerative Diseases , NeuroimagingABSTRACT
The Seoul Neuropsychological Screening Battery (SNSB) is one of the standardized neuropsychological test batteries widely used in Korea. However, it may be a bit too lengthy for patients with decreased attention span; and it does not provide the score of global cognitive function (GCF), which is useful for monitoring patients longitudinally. We sought to validate a dementia version of SNSB (SNSB-D) that was shorter than the original SNSB and contained only scorable tests with a GCF score of 300. We administered SNSB-D to patients with mild cognitive impairment (MCI) (n=43) and Alzheimer's disease (AD) (n=93), and normal controls (NC) (n=77). MCI and AD groups had GCF scores significantly different from NC group, and GCF scores were able to distinguish patients with Clinical Dementia Rating of 0.5 and 1. Test-retest reliability was high, with a correlation coefficient of 0.918 for AD, 0.999 for MCI, and 0.960 for NC. The GCF score significantly correlated with the Mini-Mental State Examination (MMSE). Through ROC-curve analysis, GCF scores were found to yield more accurate diagnoses than the MMSE. The SNSB-D is a valid, reliable tool for assessing the overall cognitive function, and can be used to monitor cognitive changes in patients with dementia.
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Humans , Alzheimer Disease/diagnosis , Cognition Disorders/diagnosis , Dementia/complications , Korea , Neuropsychological Tests/standards , ROC Curve , Reproducibility of Results , Severity of Illness IndexABSTRACT
BACKGROUND AND PURPOSE: The closing-in phenomenon is the tendency to draw near or on the target when copying figures, which has been found mostly in patients with Alzheimer's disease (AD). We attempted to quantify the degree of closing-in and to compare it between patients with AD and vascular dementia (VaD). METHODS: The subjects (55 AD, 39 VaD and 38 normal controls) were asked to copy the figure of alternating square and triangle, starting at the designated point and continuing from left to right. The patients with AD and VaD did not differ in age, education, severity of dementia or Rey Complex Figure Test copy score. The proximity (Y-axis) of the subject's drawing to the target was plotted at intervals of 2 mm along the X-axis and the degree of closing-in was computed from the slope of the regression line. RESULTS: The AD and VaD patients showed a steeper slope than the controls. There was no significant difference, however, in the magnitude of closing-in of the AD and VaD patients. When closing-in was defined as a slope that was greater than the mean+2SD of the slope observed for the controls, 32.7% of the AD and 25.6% of the VaD patients showed closing-in. CONCLUSIONS: Our study, using a new method of measuring the degree of closing-in, suggests that this phenomenon is not specific to AD.
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Humans , Alzheimer Disease , Dementia , Dementia, Vascular , EducationABSTRACT
It is not uncommon for idiopathic parkinson's disease (IPD) to occur concurrently with other degenerative dementing disorders such as Alzheimer's disease. However, there has been no report about the comorbidity of IPD and frontotemporal lobar degeneration. We report a 70-year-old man diagnosed with IPD accompanied by progressive non-fluent aphasia (PA). Brain MRI showed left frontal opercular atrophy, and an 18F-FDG PET scan revealed predominant left frontotemporal hypometabolism. It remains unknown whether or not the co-occurrence of IPD and PA was coincidental.
Subject(s)
Aged , Humans , Alzheimer Disease , Aphasia , Atrophy , Brain , Comorbidity , Dementia , Fluorodeoxyglucose F18 , Frontotemporal Lobar Degeneration , Magnetic Resonance Imaging , Parkinson Disease , Positron-Emission Tomography , Primary Progressive Nonfluent AphasiaABSTRACT
BACKGROUND: Patients with Alzheimer's disease (AD) at an early stage present with memory decline and impairments of language and visuospatial functions. However, some AD patients occasionally show frontal lobe dysfunctions in the early stage those are known to emerge only at the advanced stage. This subtype of AD is called a frontal variant of AD (frontal AD). We report neuropsychological and FDG-PET findings of three cases of frontal AD. METHODS: Three patients met the diagnostic criteria of probable AD proposed by the NINCDS-ADRDA. However, they unusually showed clinical symptoms associated with frontal lobe dysfunctions even if they were relatively in the early stage of dementia. All the patients underwent neuropsychological tests and brain FDG-PET scans. Distribution of glucose hypometabolism was analyzed using statistical parametric mappings (SPM). RESULTS: Results of neuropsychological tests were consistent with findings of AD except that frontal lobe dysfunctions were prominent. FDG-PET scans and SPM analysis of these images showed hypometabolism in the frontal as well as temporo-parietal regions. Unlike the hypometabolism pattern found in frontotemporal dementia, frontal hypometabolism in our patients was not as severe as parietal hypometablism and hypometabolic regions within the temporal lobe were in the middle or posterior part of the middle and inferior temporal gyri rather than in the anterior part. CONCLUSIONS: Detailed neuropsycholgical tests and FDG-PET may help differentiate AD with frontal involvement in its early stage (frontal AD) from frontotemporal dementia. Future studies with FDG-PET in a larger series of frontal AD cases, especially with histologically proven cases, may be needed.
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Humans , Alzheimer Disease , Brain , Dementia , Frontal Lobe , Frontotemporal Dementia , Glucose , Memory , Neuroimaging , Neuropsychological Tests , Rabeprazole , Temporal LobeABSTRACT
Korean written language is composed of ideogram (Hanja) and phonogram (Hangul), as Japanese consists of Kanji (ideogram) and Kana (phonogram). Dissociation between ideogram and phonogram impairment after brain injury has been reported in Japanese, but few in Korean. We report a 64-yr-old right-handed man who showed alexia with agraphia in Hanja but preserved Hangul reading and writing after a left posterior inferior temporal lobe infarction. Interestingly, the patient was an expert in Hanja; he had been a Hanja calligrapher over 40 yr. However, when presented with 65 basic Chinese letters that are taught in elementary school, his responses were slow both in reading (6.3 sec/letter) and writing (8.8 sec/letter). The rate of correct response was 81.5% (53 out of 65 letters) both in reading and writing. The patient's performances were beyond mean-2SD of those of six age-, sex-, and education-matched controls who correctly read 64.7 out of 65 and wrote 62.5 out of 65 letters with a much shorter reaction time (1.3 sec/letter for reading and 4.0 sec/letter for writing). These findings support the notion that ideogram and phonogram can be mediated in different brain regions and Hanja alexia with agraphia in Korean patients can be associated with a left posterior inferior temporal lesion.