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Background@#and Purpose: This study aimed to evaluate the brain magnetic resonance imaging (MRI) of patients with acute transient global amnesia (TGA) using volumetric analysis to verify whether the brains of TGA patients have pre-existing structural abnormalities. @*Methods@#We evaluated the brain MRI data from 87 TGA patients and 20 age- and sexmatched control subjects. We included brain MRIs obtained from TGA patients within 72 hours of symptom onset to verify the pre-existence of structural change. For voxel-based morphometric analyses, statistical parametric mapping was employed to analyze the structural differences between patients with TGA and control subjects. @*Results@#TGA patients exhibited significant volume reductions in the bilateral ventral anterior cingulate cortices (corrected p<0.05). @*Conclusions@#TGA patients might have pre-existing structural changes in bilateral ventral anterior cingulate cortices prior to TGA attacks.
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Background@#and Purpose: Voice, reflecting cerebral functions, holds potential for analyzing and understanding brain function, especially in the context of cognitive impairment (CI) and Alzheimer’s disease (AD). This study used voice data to distinguish between normal cognition and CI or Alzheimer’s disease dementia (ADD). @*Methods@#This study enrolled 3 groups of subjects: 1) 52 subjects with subjective cognitive decline; 2) 110 subjects with mild CI; and 3) 59 subjects with ADD. Voice features were extracted using Mel-frequency cepstral coefficients and Chroma. @*Results@#A deep neural network (DNN) model showed promising performance, with an accuracy of roughly 81% in 10 trials in predicting ADD, which increased to an average value of about 82.0%±1.6% when evaluated against unseen test dataset. @*Conclusions@#Although results did not demonstrate the level of accuracy necessary for a definitive clinical tool, they provided a compelling proof-of-concept for the potential use of voice data in cognitive status assessment. DNN algorithms using voice offer a promising approach to early detection of AD. They could improve the accuracy and accessibility of diagnosis, ultimately leading to better outcomes for patients.
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Background@#and Purpose: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a progressive decline in cognition and performance of daily activities. Recent studies have attempted to establish the relationship between AD and sleep. It is believed that patients with AD pathology show altered sleep characteristics years before clinical symptoms appear. This study evaluated the differences in sleep characteristics between cognitively asymptomatic patients with and without some amyloid burden. @*Methods@#Sleep characteristics of 76 subjects aged 60 years or older who were diagnosed with subjective cognitive decline (SCD) but not mild cognitive impairment (MCI) or AD were measured using Fitbit ® Alta HR, a wristwatch-shaped wearable device. Amyloid deposition was evaluated using brain amyloid plaque load (BAPL) and global standardized uptake value ratio (SUVR) from fluorine-18 florbetaben positron emission tomography. Each component of measured sleep characteristics was analyzed for statistically significant differences between the amyloid-positive group and the amyloid-negative group. @*Results@#Of the 76 subjects included in this study, 49 (64.5%) were female. The average age of the subjects was 70.72±6.09 years when the study started. 15 subjects were classified as amyloid-positive based on BAPL. The average global SUVR was 1.598±0.263 in the amyloidpositive group and 1.187±0.100 in the amyloid-negative group. Time spent in slow-wave sleep (SWS) was significantly lower in the amyloid-positive group (39.4±13.1 minutes) than in the amyloid-negative group (49.5±13.1 minutes) (p=0.009). @*Conclusions@#This study showed that SWS is different between the elderly SCD population with and without amyloid positivity. How SWS affects AD pathology requires further research.
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Background@#and Purpose: Reportedly 30–50% of patients being treated for chronic illnesses do not adhere to their medication regimen. We assessed the impact of a nurse-led education program for caregivers of Korean de novo Alzheimer’s disease patients who had newly been prescribed donepezil. @*Methods@#This multicenter study analyzed 93 participants in a caregiver education group and 92 participants in a caregiver no-education group. At every visit up to the end of the study (1 year), caregivers in the education group were given educational brochures regarding Alzheimer’s disease and the efficacy and adverse events of donepezil treatment. The primary endpoint was the discontinuation rate of donepezil treatment during the 1-year observation period. The secondary endpoints included the effect of education on compliance with donepezil treatment assessed at each visit using a clinician rating scale (CRS) and visual analog scale (VAS), and changes from baseline in cognitive assessment tests. @*Results@#The donepezil discontinuation rates at 1 year were 5.38% (5/93) and 6.52% (6/92) in the caregiver education and no-education groups, respectively (p=0.742). No significant between-group differences in donepezil compliance rates on the CRS and VAS were observed, but significant changes were observed in some cognitive tests from baseline to the end of the study. @*Conclusions@#Caregiver education had no significant effect on treatment discontinuation, but this may have been due to the low severity of cognitive impairment among the included population at baseline. In addition, the low discontinuation rates meant that no significant difference in treatment compliance was observed.
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Background@#and Purpose: Reportedly 30–50% of patients being treated for chronic illnesses do not adhere to their medication regimen. We assessed the impact of a nurse-led education program for caregivers of Korean de novo Alzheimer’s disease patients who had newly been prescribed donepezil. @*Methods@#This multicenter study analyzed 93 participants in a caregiver education group and 92 participants in a caregiver no-education group. At every visit up to the end of the study (1 year), caregivers in the education group were given educational brochures regarding Alzheimer’s disease and the efficacy and adverse events of donepezil treatment. The primary endpoint was the discontinuation rate of donepezil treatment during the 1-year observation period. The secondary endpoints included the effect of education on compliance with donepezil treatment assessed at each visit using a clinician rating scale (CRS) and visual analog scale (VAS), and changes from baseline in cognitive assessment tests. @*Results@#The donepezil discontinuation rates at 1 year were 5.38% (5/93) and 6.52% (6/92) in the caregiver education and no-education groups, respectively (p=0.742). No significant between-group differences in donepezil compliance rates on the CRS and VAS were observed, but significant changes were observed in some cognitive tests from baseline to the end of the study. @*Conclusions@#Caregiver education had no significant effect on treatment discontinuation, but this may have been due to the low severity of cognitive impairment among the included population at baseline. In addition, the low discontinuation rates meant that no significant difference in treatment compliance was observed.
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Background@#and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. @*Methods@#This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). @*Results@#Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. @*Conclusions@#In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.
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Background@#and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. @*Methods@#This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). @*Results@#Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. @*Conclusions@#In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.
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Background@#and Purpose: The Mini Mental State Examination, 2nd edition: Expanded version (MMSE-2: EV) involves an immediate recall (IR) of story memory (SM). A full version of SM has been developed and standardized; it includes delayed recall (DR) and recognition tests in addition to IR to increase its clinical utility as an independent story recall test. This study was conducted to provide norms for the full version of SM in the Korean version of MMSE-2: EV for clinical use. @*Methods@#A total of 1,168 participants (496 males and 672 females) were included in the study. The ages ranged from 19 to 90 years, and the education level ranged from illiterate to post-graduate. Regression analysis was used to evaluate the relative contributions of demographic variables (age, education, and sex) on the SM measures. @*Results@#We stratified age into 11 groups, and categorized the education level into 6 groups.It was found that the IR, DR, and recognition scores of SM were affected by age, education level, and sex. We provided corrected means and standard deviations of the IR, DR, and recognition scores of the SM for the demographic variables. @*Conclusions@#The results indicate the importance of considering demographic variables in interpreting the full version of SM measures. The normative data we have provided in this study should be useful in clinical and research settings for detecting the impairment in verbal memory.
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Background@#and Purpose: The Mini Mental State Examination, 2nd edition: Expanded version (MMSE-2: EV) involves an immediate recall (IR) of story memory (SM). A full version of SM has been developed and standardized; it includes delayed recall (DR) and recognition tests in addition to IR to increase its clinical utility as an independent story recall test. This study was conducted to provide norms for the full version of SM in the Korean version of MMSE-2: EV for clinical use. @*Methods@#A total of 1,168 participants (496 males and 672 females) were included in the study. The ages ranged from 19 to 90 years, and the education level ranged from illiterate to post-graduate. Regression analysis was used to evaluate the relative contributions of demographic variables (age, education, and sex) on the SM measures. @*Results@#We stratified age into 11 groups, and categorized the education level into 6 groups.It was found that the IR, DR, and recognition scores of SM were affected by age, education level, and sex. We provided corrected means and standard deviations of the IR, DR, and recognition scores of the SM for the demographic variables. @*Conclusions@#The results indicate the importance of considering demographic variables in interpreting the full version of SM measures. The normative data we have provided in this study should be useful in clinical and research settings for detecting the impairment in verbal memory.
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Neurobehavioral symptoms of dementia (NBSD) are very common and are significant symptoms of the illness, contributing most to caregiver burdens and often resulting in premature institutionalization of the person with dementia. The main symptoms of NBSD are anxiety, depression, delusions, and hallucinations. NBSD produce significant problems for both patients and caregivers. The pathophysiology of NBSD is determined by genetic, structural, or environmental factors. Therefore, treatment of NBSD requires continuous and organic cooperation between patients, caregivers, social environments, and doctors. Therefore, it is important for neurologists, who mainly view NBSD for dementia patients, to increase their understanding of these more comprehensive areas as well as the latest insights and treatments to help patients and caregivers.
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Background@#and Purpose: To identify biomarkers for prediction of the progression to dementia in mild cognitive impairment (MCI) patients, evaluation of brain structure changes has been validated by a comprehensive visual grading scale (CVRS) through magnetic resonance imaging (MRI). In this study, we specifically elucidated for the cognitive change of MCI patients classified based on AT(N) pathological status classification during the follow-up period of 3 years through the CVRS. @*Methods@#The 301 patients with initial MCI visited at least once for follow-up period. The data used in this study were obtained from the Alzheimer's disease (AD) Neuroimaging Initiative study. Brain atrophy was assessed by CVRS using MRI. AT(N) profiles were classified by cerebrospinal fluid abnormality. Based on the AT(N) assessment, all individuals in this study were divided into 3 groups (normal state biomarker, suspected non-Alzheimer's pathology [SNAP], or Alzheimer's continuum). The cox regression was used to analyze the hazard ratios of CVRS for progression to dementia. @*Results@#Sixty-three progressed and 238 remained stable to dementia and the CVRS (mean±standard deviation) had significant difference between progressive MCI and stable MCI (p<0.001). Univariate and multivariate cox regression results (p<0.001) showed the independence of initial CVRS as a predictor for the progression to dementia. Moreover, comparing the classified AT(N) pathology group, SNAP and AD, effectiveness of CVRS as a predictor was verified only in Alzheimer's continuum. @*Conclusions@#The initial CVRS score as a predictor of dementia progression was independently validated at the stage of Alzheimer's progression among AT(N) pathologically differentiated MCI.
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Background@#and Purpose: To identify biomarkers for prediction of the progression to dementia in mild cognitive impairment (MCI) patients, evaluation of brain structure changes has been validated by a comprehensive visual grading scale (CVRS) through magnetic resonance imaging (MRI). In this study, we specifically elucidated for the cognitive change of MCI patients classified based on AT(N) pathological status classification during the follow-up period of 3 years through the CVRS. @*Methods@#The 301 patients with initial MCI visited at least once for follow-up period. The data used in this study were obtained from the Alzheimer's disease (AD) Neuroimaging Initiative study. Brain atrophy was assessed by CVRS using MRI. AT(N) profiles were classified by cerebrospinal fluid abnormality. Based on the AT(N) assessment, all individuals in this study were divided into 3 groups (normal state biomarker, suspected non-Alzheimer's pathology [SNAP], or Alzheimer's continuum). The cox regression was used to analyze the hazard ratios of CVRS for progression to dementia. @*Results@#Sixty-three progressed and 238 remained stable to dementia and the CVRS (mean±standard deviation) had significant difference between progressive MCI and stable MCI (p<0.001). Univariate and multivariate cox regression results (p<0.001) showed the independence of initial CVRS as a predictor for the progression to dementia. Moreover, comparing the classified AT(N) pathology group, SNAP and AD, effectiveness of CVRS as a predictor was verified only in Alzheimer's continuum. @*Conclusions@#The initial CVRS score as a predictor of dementia progression was independently validated at the stage of Alzheimer's progression among AT(N) pathologically differentiated MCI.
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BACKGROUND@#AND PURPOSE: We aimed to determine the reliability and validity of a short form of the Korean Dementia Screening Questionnaire-Cognition (KDSQ-C) as a screening tool for cognitive dysfunction.@*METHODS@#This study recruited 420 patients older than 65 years and their informants from 11 hospitals, and categorized the patients into normal cognition, mild cognitive impairment, and dementia subgroups. The KDSQ-C was completed separately by the patients and their informants. We abstracted three components of the KDSQ-C and combined these components into the following four subscales: KDSQ-C-I (items 1–5, memory domain), KDSQ-C-II (items 1–5 & 11–15, memory domain+activities of daily living), KDSQ-C-III (items 1–5 & 6–10, memory domain+other cognitive domains), and KDSQ-C-IV (items 6–10 & 11–15, other cognitive domains+activities of daily living). The reliability and validity were compared between these four subscales.@*RESULTS@#A receiver operating characteristic (ROC) analysis of questionnaire scores provided by the patients showed that the areas under the ROC curves (AUCs) for the KDSQ-C, KDSQC-I, and KDSQ-C-II for diagnosing dementia were 0.75, 0.72, and 0.76, respectively; the corresponding AUCs for informant-completed questionnaires were 0.92, 0.89, and 0.92, indicating good discriminability for dementia.@*CONCLUSIONS@#A short form of the patient- and informant-rated versions of the KDSQ-C (KDSQ-C-II) is as capable as the 15-item KDSQ-C in screening for dementia.
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Diagnostic guidelines for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease (AD) were released by the National Institute on Aging and Alzheimer's Association (NIA-AA) in 2011. Promoted by the subsequent scientific progress, a unifying update, the ‘NIA-AA Research Framework', was published in 2018. This new research framework shifts the definition of AD from syndrome to biological construct based on biomarkers in living people. The biomarkers were grouped into β amyloid deposition (A), pathologic tau (T), and neurodegeneration (N) related, termed the ‘AT(N) classification system#x2019;, which could be extended with new biomarkers as they become available in the future. For the staging of cognitive impairment, three syndromal stages for observational studies and six numeric stages for clinical trials were also suggested. This biomarker-based classification combined with clinical staging is expected to enhance the understanding of AD as well as aid in precise targeting for interventional clinical trials. This review focused on the introduction of the new 2018 NIA-AA Research Framework. Although this framework has been proposed for research purposes, it is expected to be adopted into general clinical practice with thorough examination and validation in the future.
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Enfermedad de Alzheimer , Biomarcadores , Clasificación , Trastornos del Conocimiento , Demencia , Disfunción Cognitiva , Placa AmiloideRESUMEN
BACKGROUND AND PURPOSE: During transient global amnesia (TGA), selective impairment of episodic memory is assumed to occur due to alteration in the neuronal network between the hippocampus and parietooccipital cortices that also include a hub for smooth pursuit (SP) eye movements. This study aimed to determine whether SP is impaired during TGA, and to identify any anatomical and functional linkage present between the oculomotor and memory systems. METHODS: Within a median of 1.0 day of TGA, horizontal SP was evaluated in 145 patients with a target moving at peak velocities of 10°/s and 20°/s. The average SP gains of patients were compared with those of the age-matched controls. RESULTS: The patients with TGA showed lower SP gains in both directions for both peak target velocities. While the normal controls showed symmetric SP in the rightward and leftward directions, in the TGA patients the SP gain was lower during rightward than leftward SP regardless of bilaterality or the side of the lesions. CONCLUSIONS: The cortical regions processing information about visual motion appeared to be affected during or soon after an amnestic episode of TGA, and more so in the right hemisphere. This means that disturbed processing of dynamic visual information may be related to the impaired spatial orientation observed during TGA.
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Humanos , Amnesia Global Transitoria , Movimientos Oculares , Hipocampo , Memoria , Memoria Episódica , Neuronas , Seguimiento Ocular UniformeRESUMEN
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.
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Humanos , Enfermedad de Alzheimer , Cuidadores , Cognición , Trastornos del Conocimiento , Recolección de Datos , Demencia , Corea (Geográfico) , Tamizaje Masivo , Memoria , Disfunción Cognitiva , Curva ROC , Autoevaluación (Psicología)RESUMEN
BACKGROUND: Normal pressure hydrocephalus (NPH) is an etiology of dementia that is reversible following cerebrospinal fluid shunt placement, however, surgical intervention not always clinically effective and the respons to shunt therapy is poorly understood. Furthermore, NPH is a source of comorbidity in diseases with neurodegenerative pathology, such as Alzheimer's disease (AD). CASE REPORT: A 61-year-old woman presented to the neurology clinic with progressive gait difficulties and cognitive impairment over five years. Nine years after ventriculoperitoneal (VP) shunt treatment, the patient began to experience frequent falls. There was no improvement in clinical symptoms after the alteration of valve pressure on the VP shunt. An 18F-florbetaben amyloid positron emission tomography scan showed increased diffusion uptake over the bilateral cortices, precuneus, and posterior cingulate cortex. CONCLUSIONS: The patient of NPH was unresponsive to shunt therapy due to the development of AD.
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Femenino , Humanos , Persona de Mediana Edad , Accidentes por Caídas , Enfermedad de Alzheimer , Amiloide , Derivaciones del Líquido Cefalorraquídeo , Trastornos del Conocimiento , Comorbilidad , Demencia , Difusión , Marcha , Giro del Cíngulo , Hidrocefalia , Hidrocéfalo Normotenso , Neurología , Lóbulo Parietal , Patología , Tomografía de Emisión de PositronesRESUMEN
BACKGROUND AND PURPOSE: During the Vietnam War, many Korean soldiers were exposed to Agent Orange. Until now, there existed only limited evidence of association between exposure to Agent Orange and Alzheimer's disease (AD). The main pathological feature of AD is brain amyloidosis. To explore the pathophysiological characteristic of AD with Agent Orange exposure, we compared newly developed amyloid beta (Aβ) oligomer levels in plasma between AD with Agent Orange exposure and without exposure. METHODS: We recruited 48 AD patients with Agent Orange exposure and 66 AD patients without Agent Orange. Using the Multimer Detection System technique, which was based on an enzyme-linked immunosorbent assay, we measured Aβ oligomers in the plasma of study subjects. RESULTS: Compared to normal control patients, plasma Aβ oligomer levels were higher in AD patients regardless of history of Agent Orange exposure. However, AD patients with Agent Orange exposure showed higher plasma Aβ oligomer levels than AD patients without Agent Orange. DISCUSSION: This study showed higher plasma Aβ oligomer levels in AD patients with Agent Orange exposure compared to AD patients without Agent Orange. This finding suggests the possibility of a different pathophysiology of AD patients with Agent Orange exposure from AD patients without Agent Orange.
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Humanos , Enfermedad de Alzheimer , Amiloide , Amiloidosis , Encéfalo , Citrus sinensis , Ensayo de Inmunoadsorción Enzimática , Personal Militar , Plasma , VietnamRESUMEN
Machine learning is where a machine (i.e., computer) determines for itself how input data is processed and predicts outcomes when provided with new data. An artificial neural network is a machine learning algorithm based on the concept of a human neuron. The purpose of this review is to explain the fundamental concepts of artificial neural networks.