ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Subject(s)
Humans , Area Under Curve , Cognition , Dementia , Mass Screening , Memory , Cognitive Dysfunction , Reproducibility of Results , ROC Curve , Self Report , Self-AssessmentABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Alzheimer Disease , Biomarkers , Classification , Cognition Disorders , Dementia , Cognitive Dysfunction , Plaque, AmyloidABSTRACT
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.
Subject(s)
Humans , Alzheimer Disease , Caregivers , Cognition , Cognition Disorders , Data Collection , Dementia , Korea , Mass Screening , Memory , Cognitive Dysfunction , ROC Curve , Self-AssessmentABSTRACT
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.
Subject(s)
Humans , Amnesia, Transient Global , Eye Movements , Hippocampus , Memory , Memory, Episodic , Neurons , Pursuit, SmoothABSTRACT
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.
Subject(s)
Aged , Humans , Alzheimer Disease , Atrophy , Cognition Disorders , Dementia , Diagnosis , Korea , Pemetrexed , ROC CurveABSTRACT
BACKGROUND AND PURPOSE: Several studies have validated the clinical efficacy of computerized cognitive training applications. However, few studies have investigated the neural substrates of these training applications using simultaneous multimodal neuroimaging modalities. We aimed to determine the effectiveness of computerized cognitive training and corresponding neural substrates through a multimodal approach. METHODS: Ten patients with mild cognitive impairment (MCI), six patients with subjective memory impairment (SMI), and 10 normal controls received custom-developed computerized cognitive training in the memory clinic of a university hospital. All of the participants completed 24 sessions of computerized cognitive training, each lasting 40 minutes and performed twice weekly. They were assessed using neuropsychological tests (both computerized and conventional), electroencephalography, fluorodeoxyglucose positron-emission tomography (FDG-PET), volumetric magnetic resonance imaging (MRI), and diffusion-tensor imaging (DTI) at pre- and posttraining. RESULTS: The patients with MCI exhibited significant improvements in the trail-making test–black & white-B, and memory domain of the computerized cognitive assessment. Subjects with normal cognition exhibited significant improvements in scores in the language and attention-/psychomotor-speed domains. There were no significant changes in subjects with SMI. In the pre- and posttraining evaluations of the MCI group, FDG-PET showed focal activation in the left anterior insula and anterior cingulate after training. Volumetric MRI showed a focal increase in the cortical thickness in the rostral anterior cingulate. DTI revealed increased fractional anisotropy in several regions, including the anterior cingulate. CONCLUSIONS: The anterior cingulate and anterior insula, which are parts of the salience network, may be substrates for the improvements in cognitive function induced by computerized cognitive training.
Subject(s)
Humans , Anisotropy , Cognition , Electroencephalography , Gyrus Cinguli , Magnetic Resonance Imaging , Memory , Cognitive Dysfunction , Neuroimaging , Neuropsychological Tests , Positron-Emission Tomography , Treatment OutcomeABSTRACT
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.
Subject(s)
Humans , Artificial Intelligence , Machine Learning , Mathematics , NeuronsABSTRACT
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.
Subject(s)
Humans , Alzheimer Disease , Amyloid , Amyloidosis , Brain , Citrus sinensis , Enzyme-Linked Immunosorbent Assay , Military Personnel , Plasma , VietnamABSTRACT
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.
Subject(s)
Female , Humans , Middle Aged , Accidental Falls , Alzheimer Disease , Amyloid , Cerebrospinal Fluid Shunts , Cognition Disorders , Comorbidity , Dementia , Diffusion , Gait , Gyrus Cinguli , Hydrocephalus , Hydrocephalus, Normal Pressure , Neurology , Parietal Lobe , Pathology , Positron-Emission TomographyABSTRACT
In cases of multiple facial trauma and other specific cases, the anesthesiologist may be asked to convert an oral endotracheal tube to a nasal endotracheal tube or vice versa. Conventionally, the patient is simply extubated and the endotracheal tube is re-inserted along either the oral or nasal route. However, the task of airway management can become difficult due to surgical trauma or worsening of the airway condition. Fiberoptic bronchoscopy was considered a novel method of airway conversion but this method is not useful when there are secretions and bleeding in the airway, or if the anesthesiologist is inexperienced in using this device. We report a successful airway conversion under the aid of both, a fiberoptic bronchoscope and a C-MAC video laryngoscope.