Impact of an Education Program for Caregivers of Patients with Alzheimer’s Disease on Treatment Discontinuation and Compliance in Korea

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.

Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer’s Disease Patients in Asia

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.

Validation of a New Screening Tool for Dementia: The Simple Observation Checklist for Activities of Daily Living

Background@#and Purpose Screening tests for dementia such as the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment are widely used, but there are drawbacks to their efficient use. There remains a need for a brief and easy method of assessing the activities of daily living (ADL) that can be administered to elderly individuals by healthcare workers. We have therefore developed a new scale named the Simple Observation Checklist for Activities of Daily Living (SOC-ADL). @*Methods@#We developed the SOC-ADL scale as a team of experts engaged in caring for individuals with dementia. This scale comprises eight items and was designed based on the Korean instrumental activities of daily living (K-IADL) scale and the Barthel activities of daily living scale (Barthel Index). The new scale was validated by enrolling 176 patients with cognitive dysfunction across 6 centers. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were performed. We assessed its concurrent validity by performing comparisons with the Korean-MMSE, Clinical Dementia Rating, Clinical Dementia Rating-Sum of Boxes, K-IADL, and Barthel Index, and its criterion validity by performing comparisons between mild cognitive impairment (MCI) and dementia. We also used Cronbach’s alpha to assess the interitem reliability. The appropriate cutoff values were determined by analyzing receiver operating characteristic curves, including the areas underneath them. @*Results@#EFA extracted one factor and CFA revealed that all of the model fits exceeded the minimum acceptable criteria. The SOC-ADL scores were strongly correlated with those of the other tools for dementia and could be used to differentiate MCI from dementia. Cronbach’s alpha values indicated that the results were reliable. The optimal cutoff value of the SOC-ADL for discriminating dementia from MCI was 3 points, which provided a sensitivity and specificity of 74.5% and 75.7%, respectively. @*Conclusions@#Our results demonstrate that the SOC-ADL is a valid and reliable tool for differentiating dementia from MCI based on an assessment of ADL. This new tool can be used for screening ADL in elderly subjects who have difficulty communicating, and to increase the efficiency of dementia screening at the population level.

Impact of an Education Program for Caregivers of Patients with Alzheimer’s Disease on Treatment Discontinuation and Compliance in Korea

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.

Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer’s Disease Patients in Asia

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.

Clinical Aspects of Neurobehavioral Symptoms of Dementia

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.

Effect of Paper-Based Cognitive Training in Early Stage of Alzheimer's Dementia

BACKGROUND AND PURPOSE: Cognitive training refers to a series of standardized tasks with inherent challenges that target specific cognitive domains. Positive outcome of cognitive training in persons with Alzheimer's disease has been reported. In this study, the objective was to design sets of cognitive training program, “Gipum-seo” which is combined cognitive training, consists of different levels of difficulty using predesigned paper-and-pencil exercises. Also, to evaluate the effects of the cognitive training on patients' with early stage of Alzheimer's disease. METHODS: The subjects for this study were forty participants who were diagnosed with early stage of Alzheimer's dementia. To test the efficacy of paper-based cognitive training programs to cognition, all patients were randomly grouped to either an intervention group (n=20) or a control group (n=20). The intervention group regularly received 24 sessions of paper-based cognitive training over a 12-week period. Neuropsychological examinations were conducted before and after this training period. RESULTS: After the 12 weeks, the intervention group showed a significant change in Korean version of the Mini-Mental State Examination (25.90±3.8), compared to the control group (23.7±2.8) (p=0.042). The training group also showed a significant improvement in language, attention and executive function, as compared with controls. CONCLUSIONS: Paper-based cognitive training might have beneficial effects on the general cognitive functions in the early stage of Alzheimer's dementia.

Improvement of Post Stroke Echolalia after Using Selective Serotonin Reuptake Inhibitors

No abstract available.

A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial for Efficacy of Acetyl-L-carnitine in Patients with Dementia Associated with Cerebrovascular Disease

BACKGROUND AND PURPOSE: Acetyl-L-carnitine (ALC) is a widely used drug for various neurodegenerative diseases including dementia. The aim of the present study was to elucidate the efficacy of ALC in dementia patients with cerebrovascular disease (vascular cognitive impairment; VCI). METHODS: Fifty-six patients were randomized to treatment with 500 mg ter in die ALC, or placebo in this 28-week, double-blind, placebo-controlled trial. The primary outcome measure was the Korean version of Montreal Cognitive Assessment (MoCA-K). RESULTS: Following treatment with ALC, the cognitive function measured by the MoCA-K was significantly improved in the ALC-treated groups. However, other secondary outcomes were not statistically significant between ALC- and placebo-treated groups. In MoCA-K analysis, attention and language sub-items significantly favored the ALC-treated group. CONCLUSIONS: Compared with placebo, treatment with ALC 1,500 mg/day produced significant changes in MoCA-K in dementia patients with VCI. ALC was well tolerated in this population. Despite the study limitations, the findings suggested the potential benefits associated with the use of ALC in dementia patients with VCI.

FDG PET Findings according to Wandering Patterns of Patients with Drug-naïve Alzheimer's Disease

BACKGROUND AND PURPOSE: To explore anatomic substrate of specific wandering patterns in patients with Alzheimer's disease (AD) by performing positron emission tomography with 18F fluorodeoxyglucose positron emission tomography (FDG PET). METHODS: Drug-naïve AD patients with wandering (n=80) and without wandering (n=262) were recruited. First, the specific pattern of wandering type was operationally classified according to specific wandering score and clinical assessment. Second, brain FDG PET was performed and fluorodeoxyglucose (FDG) uptake differences of specific brain regions according to wandering patterns were compared to those of non-wanderers. RESULTS: In patients with pacing pattern, FDG PET showed significant lower FDG uptake in both middle cingulum and left putamen cluster compared to non-wanderers. The right precuneus and supplementary motor area in patients with random pattern and left calcarine sulcus, right calcarine sulcus, right middle cingulum, and right post central gyrus in patients with lapping pattern had significantly lower FDG uptake compared to non-wanderers. CONCLUSIONS: This study showed that wandering in patients with AD had three distinct patterns. These specific patterns showed significant lower FDG uptake in specific brain areas compared to non-wanderers.

Plasma Oligomeric Beta Amyloid in Alzheimer's Disease with History of Agent Orange Exposure

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.

Brain Perfusion Correlates of Apathy in Alzheimer's Disease

BACKGROUND AND PURPOSE: Apathy is one of the most common neuropsychiatric symptoms in patients with Alzheimer's disease (AD). It may have adverse impacts on the progression of AD. However, its neurobiological underpinnings remain unclear. The objective of this study was to investigate differences in regional cerebral blood flow (rCBF) between AD patients with apathy and those without apathy. METHODS: Sixty-six apathetic AD patients and 66 AD patients without apathy completed Neuropsychiatric Inventory (NPI) and underwent technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT) scans. Voxel-wise differences in rCBF between the 2 groups were examined. Association between rCBF and levels of apathy in the apathetic group was also assessed. RESULTS: AD patients with apathy showed lower rCBF in the bilateral orbitofrontal cortex, left putamen, left nucleus accumbens, left thalamus, and bilateral insula than those without (all p < 0.005). Mean perfusion across all significant clusters showed a negative linear correlation with NPI apathy score in AD patients with apathy (β = −0.25; p = 0.04). CONCLUSIONS: Hypoperfusion in the prefrontal, striatal, and insular areas may be neural correlates of apathy in AD patients.

Gait Patterns in Parkinson's Disease with or without Cognitive Impairment

BACKGROUND AND PURPOSE: Cognitive and gait disturbance are common symptoms in Parkinson's disease (PD). Although the relationship between cognitive impairment and gait dysfunction in PD has been suggested, specific gait patterns according to cognition are not fully demonstrated yet. Therefore, the aim of this study was to investigate gait patterns in PD patients with or without cognitive impairment. METHODS: We studied 86 patients at an average of 4.8 years after diagnosis of PD. Cognitive impairment was defined as scoring 1.5 standard deviation below age- and education-specific means on the Korean version of the Mini-Mental State Examination (K-MMSE). Three-dimensional gait analysis was conducted for all patients and quantified gait parameters of temporal-spatial data were used. Relationships among cognition, demographic characteristics, clinical features, and gait pattern were evaluated. RESULTS: Cognitive impairment was observed in 41 (47.7%) patients. Compared to patients without cognitive impairment, patients with cognitive impairment displayed reduced gait speed, step length, and stride length. Among K-MMSE subcategories, “registration,”“attention/calculation,” and “visuospatial function” were significantly associated with speed, step length, and stride length. However, age, disease duration, Hoehn-Yahr (HY) stage, or Unified Parkinson's Disease Rating Scale (UPDRS) motor score was not significantly related to any gait analysis parameter. CONCLUSIONS: Our present study shows that cognitive impairment is associated with slow and short-stepped gait regardless of HY stage or UPDRS motor score, suggesting that cognitive impairment may serve as a surrogate marker of gait disturbance or fall in PD patients.

Persistent Hiccup Treated by Levetiracetam

No abstract available.

Changes in Regional Cerebral Perfusion after Nicergoline Treatment in Early Alzheimer's Disease: A Pilot Study

BACKGROUND AND PURPOSE: Nicergoline is an ergoline derivative that is used to treat cognitive deficits in cerebrovascular disease and various forms of dementia. Although therapeutic effects of nicergoline have been established, little is known about its effects on cerebral perfusion in Alzheimer's disease (AD). The aim of this study was to examine the role of nicergoline in regional cerebral blood flow (rCBF) of AD patients using technetium-99m hexa-methyl-propylene-amine-oxime single photon emission computed tomography (SPECT). METHODS: Sixteen patients with early AD underwent a comprehensive clinical assessment including cognitive testing and SPECT scans before and after nicergoline treatment. Nicergoline (30 mg twice daily) was administered for an average duration of 1.5 years. Clinical and cognitive functioning was assessed using the Mini-Mental State Examination, Clinical Dementia Rating (CDR), CDR-Sum of Boxes, Global Deterioration Scale, Barthel Activities of Daily Living Index, Instrumental Activities of Daily Living, and Geriatric Depression Scale. RESULTS: Nicergoline treatment induced changes in the severity of dementia, cognitive function, activities of daily living, and depressive symptoms, which were not statistically significant. During the follow-up, the patients showed significant increases in their relative rCBF in the superior frontal gyrus, precentral gyrus, and postcentral gyrus. CONCLUSIONS: Nicergoline treatment improves perfusion of the frontal and parietal regions in early AD patients. It is possible that the increased perfusion in the superior frontal gyrus may be related to the mechanisms that delay or prevent progressive deterioration of cognitive functions in AD.

Improvement of Cognitive Function after Computer-Based Cognitive Training in Early Stage of Alzheimer's Dementia

BACKGROUND AND PURPOSE: Cognitive training is known to be an effective tool in enhancing cognitive functioning. Research has also shown that playing video game improves certain aspects of visual attention and cognitive processing speed. The effect of computer-based cognitive training has not been demonstrated so far. This study therefore evaluated whether computer-based cognitive training improved the cognitive abilities in patients with early stage of Alzheimer's dementia. METHODS: Totally, 20 participants (early stage of Alzheimer's dementia) participated in this study. To test the effectiveness of computer-based cognitive training programs to cognition, all patients were randomly allocated to either an intervention group (n=10) or a control group (n=10). The intervention group regularly received 24 sessions of computer-based cognitive training, over a 12 week period. Neuropsychological examinations were conducted before and after this training period. RESULTS: After 12 weeks, the intervention group showed a significant change in language of Korean version of the Mini-Mental State Examination (K-MMSE), compared with the baseline cognitive examinations. Also, there was greater improvement in language, attention, calculation, verbal memory, and frontal function for the experimental group, as compared with controls. CONCLUSIONS: Computer-based cognitive training might have beneficial effects on the general cognitive functions in early stage of Alzheimer's dementia.

Cerebral Perfusion Changes after Acetyl-L-Carnitine Treatment in Early Alzheimer's Disease Using Single Photon Emission Computed Tomography

BACKGROUND AND PURPOSE: Although acetyl-L-carnitine (ALC) treatment may have beneficial effects on Alzheimer's disease (AD), its underlying neural correlates remain unclear. The purpose of this study was to investigate cerebral perfusion changes after ALC treatment in AD patients using technetium-99m hexamethylpropylene amine oxime single photon emission computed tomography (SPECT). METHODS: A total of 18 patients with early AD were prospectively recruited and treated with ALC at 1.5 g/day for 1.4±0.3 years. At baseline and follow-up, brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI) were used to assess participants. After ALC administration, changes in brain perfusion, severity of dementia, cognitive performance, and neuropsychiatric disturbances were examined. RESULTS: After ALC administration, changes in scores of MMSE, CDR, GDS, and NPI were not statistically significant (p>0.05). Voxel-wise whole-brain image analysis revealed that perfusion was significantly (p<0.001) increased in the right precuneus whereas perfusion was reduced in the left inferior temporal gyrus (p<0.001), the right middle frontal gyrus (p<0.001), and the right insular cortex (p=0.001) at follow-up. CONCLUSIONS: Although previous studies have suggested that AD patients generally demonstrate progressive deterioration in brain perfusion and clinical symptoms, this study reveals that the perfusion of the precuneus is increased in AD patients after ALC administration and their cognitive and neuropsychiatric symptoms are not aggravated. Further studies are warranted to determine the potential association between perfusion increase in the precuneus and clinical symptoms after ALC treatment in AD patients.

Anxiety in Dementia

Until recently, there is considerable mess regarding the nature of anxiety in dementia. However, anxiety is common in this population affecting from 8% to 71% of prevalence, and resulted in poor outcome and quality of life, even after controlling for depression. Because a presentation of anxiety in the context of dementia can be different from typical early-onset anxiety disorder, it is not easy one to identify and quantify anxiety reliably. Moreover, differentiating anxiety from the depression and/or dementia itself also can be formidable task. Anxiety gradually decreases at the severe stages of dementia and this symptom may be more common in vascular dementia than in Alzheimer's disease. Due to the lack of large randomized clinical trials, optimal treatment and the true degree of efficacy of treatment is not clear yet in this population. However, these treatments can reduce adverse impact of anxiety on patients and caregivers. This article provides a brief review for the diagnosis, evaluation and treatment of anxiety in dementia.

Brain Abscess Caused by Vancomycin-Resistant Enterococci

No abstract available.

18F-FP-CIT Positron Emission Tomography for Correlating Motor and Cognitive Symptoms of Parkinson's Disease

BACKGROUND AND PURPOSE: The aim of this paper was to investigate the utility of 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography (PET) for evaluating the severity of Parkinson's disease (PD) according to various clinical stages, and to identify the relationship between the striatal substructure and the Unified Parkinson's Disease Rating Scale (UPDRS) motor score, cognitive symptoms through 18F-FP-CIT PET. METHODS: We retrospectively identified 542 patients with various clinical stages of PD who underwent an 18F-FP-CIT PET at our clinics. The difference between the 18F-FP-CIT PET according to the Hoehn-Yahr stage, correlation between 18F-FP-CIT PET and the UPDRS III grouped motor items, and the Korean Mini-Mental State Examination (K-MMSE) were investigated. RESULTS: As disease progressed, the right caudate and both the anterior putamen and caudate/putamen ratios exhibited a significantly lower uptake. The uptake of all striatal substructures was significantly correlated with the UPDRS total motor score. The right caudate nucleus was significantly related to both the UPDRS tremor items and the right UPDRS akinesia-rigidity items. The left caudate nucleus was related to both the UPDRS tremor items and UPDRS akinesia-rigidity items. The right anterior putamen was related to the axial items, right tremor and akinesia-rigidity items; while the left anterior putamen was related to the right tremor and right akinesia-rigidity items. Both of the posterior putamens were related to the axil items, left tremor and left akinesia rigidity items. K-MMSE was not significantly related to any striatal substructures. CONCLUSIONS: The UPDRS total motor score was significantly correlated with the uptake of all striatal substructures. However, the 18F-FPCIT uptake in specific striatal substructures was rather complexly correlated with the UPDRS motor grouped items and was not significantly related to K-MMSE. These results suggest the possibility of the complex pathophysiology of motor symptoms of PD and limitation of 18F-FPCIT PET for the evaluation of the severity of PD motor and cognitive symptoms.