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Alzheimer’s disease (AD) is the most-common cause of neurodegenerative dementia, and it is characterized by abnormal amyloid and tau accumulation, which indicates neurodegeneration. AD has mostly been diagnosed clinically. However, ligand-specific positron emission tomography (PET) imaging, such as amyloid PET, and cerebrospinal fluid (CSF) biomarkers are needed to accurately diagnose AD, since they supplement the shortcomings of clinical diagnoses. Using biomarkers that represent the pathology of AD is essential (particularly when disease-modifying treatment is available) to identify the corresponding pathology of targeted therapy and for monitoring the treatment response. Although imaging and CSF biomarkers are useful, their widespread use is restricted by their high cost and the discomfort during the lumbar puncture, respectively. Recent advances in AD blood biomarkers shed light on their future use for clinical purposes. The amyloid β (Aβ)42/Aβ40 ratio and the concentrations of phosphorylated tau at threonine 181 and at threonine 217, and of neurofilament light in the blood were found to represent the pathology of Aβ, tau, and neurodegeneration in the brain when using automatic electrochemiluminescence technologies, single-molecule arrays, immunoprecipitation coupled with mass spectrometry, etc. These blood biomarkers are imminently expected to be incorporated into clinical practice to predict, diagnose, and determine the stage of AD. In this review we focus on advancements in the measurement technologies for blood biomarkers and the promising biomarkers that are approaching clinical application.We also discuss the current limitations, the needed further investigations, and the perspectives on their use.
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This study examined the effect of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet of the Korean multi-domain dementia prevention program on the cognitive functions of the elderly with dementia risk factors. We developed the program including nutrition, exercise, cognitive training, vascular disease prevention, and motivation. One- hundred and fifty-three participants aged 60∼79 years with at least 1 dementia risk factor were randomly assigned in a 1:1:1 ratio to the facility-based intervention (FMI), home-based intervention (HMI), and the control group. The nutrition education program consisted of 10 classes over 24 weeks: the FMI received 7 group sessions and three 1:1 sessions, the HMI received 4 group sessions and three 1:1 sessions with 3 homework sessions. The Nutrition Quotient for Elderly (NQ-E) and the Mini Nutritional Assessment (MNA) were used to evaluate nutritional status. The Repeatable Battery for the Assessment Neuropsychological Status (RBANS), Korean Mini-Mental State Examination (K-MMSE), and the Cognitive Complaint Interview (CCI) were used to evaluate cognitive functions. A total of 136 people completed the program with an 11.1% dropout rate. The NQ-E (P=0.009) and RBANS (P=0.001) scores significantly increased in the FMI (N=45) and HMI (N=49) groups compared to the control group (N=42) after the study. The changes in the score of MNA and CCI did not differ significantly between groups. In conclusion, the nutritional intervention which focused on the MIND diet as a part of a multi-domain intervention program had a positive effect on the improvement of healthy eating habits and cognitive function scores in the high-risk dementia group.
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We report herein a 78-year-old woman with insidiously progressive cognitive impairment and asymmetric amyloid deposition and neurodegeneration. Brain magnetic resonance imaging revealed remarkable atrophy in the right-sided temporal lobe and hippocampus. Early dynamic 18F-flutemetamol brain amyloid positron-emission tomography images showed decreased uptake in the right temporoparietal regions. Delayed images revealed amyloid deposition which was most remarkable in the right frontotemporoparietal regions. Asymmetries of amyloid burden and neuronal dysfunction are positively correlated in Alzheimer’s disease in cortical regions with high amyloid load.
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We report a 61-year-old woman with clinical course for Alzheimer’s disease (AD) dementia and discordant amyloid-β positron-emission tomography (PET) and cerebrospinal fluid biomarkers. Brain magnetic resonance imaging revealed remarkable atrophy in the hippocampus. However, repeated delayed 18F-flutemetamol brain amyloid PET images with 1 year-interval revealed no amyloid deposition, whereas her CSF revealed low Aβ42, high total tau and p-tau181. This discordant amyloid-β PET and CSF biomarkers in this early-onset AD dementia might be associated with her low resilience or mixed pathology.
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We report herein a 78-year-old woman with insidiously progressive cognitive impairment and asymmetric amyloid deposition and neurodegeneration. Brain magnetic resonance imaging revealed remarkable atrophy in the right-sided temporal lobe and hippocampus. Early dynamic 18F-flutemetamol brain amyloid positron-emission tomography images showed decreased uptake in the right temporoparietal regions. Delayed images revealed amyloid deposition which was most remarkable in the right frontotemporoparietal regions. Asymmetries of amyloid burden and neuronal dysfunction are positively correlated in Alzheimer’s disease in cortical regions with high amyloid load.
ABSTRACT
We report a 61-year-old woman with clinical course for Alzheimer’s disease (AD) dementia and discordant amyloid-β positron-emission tomography (PET) and cerebrospinal fluid biomarkers. Brain magnetic resonance imaging revealed remarkable atrophy in the hippocampus. However, repeated delayed 18F-flutemetamol brain amyloid PET images with 1 year-interval revealed no amyloid deposition, whereas her CSF revealed low Aβ42, high total tau and p-tau181. This discordant amyloid-β PET and CSF biomarkers in this early-onset AD dementia might be associated with her low resilience or mixed pathology.
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Background@#and PurposeThe prevalence of dementia is increasing in South Korea. Multidomain interventions may be useful for preventing dementia. Such programs need to be disseminated to elderly Koreans throughout the country. We have developed programs of the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), which consists of a facility-based multidomain intervention (FMI) program and a home-based multidomain intervention (HMI) program suitable for elderly Koreans. We aim to determine the feasibility of the SUPERBRAIN programs before a large-scale randomized controlled trial. @*Methods@#We will recruit 150 participants among those without dementia aged 60–79 years with at least 1 modifiable dementia risk factor. They will be randomly assigned in a 1:1:1 ratio to the FMI, HMI, and the waiting-list control arm. The 6-month multidomain intervention consists of management of metabolic and vascular risk factors, cognitive training and social activity, physical exercise, nutritional guidance, and motivational enhancement programs. The primary outcomes are adherence and retention rates and changes in the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to the study end. The main secondary outcomes are disability, depressive symptoms, quality of life, vascular risk factors, physical performance, nutritional assessment, and motivation questionnaire. There will be an exploratory evaluation of neurotrophic, neurodegeneration, and neuroinflammation factors, microbiome, telomere length, electroencephalography, and neuroimaging measures. @*Conclusions@#The results obtained will provide information on the applicability of these multidomain intervention programs to at-risk elderly people.
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BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk for dementia. The effects of hypoglycemia on dementia are controversial. Thus, we evaluated whether hypoglycemia increases the risk for dementia in senior patients with T2DM.METHODS: We used the Korean National Health Insurance Service Senior cohort, which includes >10% of the entire senior population of South Korea. In total, 5,966 patients who had ever experienced at least one episode of hypoglycemia were matched with those who had not, using propensity score matching. The risk of dementia was assessed through a survival analysis of matched pairs.RESULTS: Patients with underlying hypoglycemic events had an increased risk for all-cause dementia, Alzheimer's dementia (AD), and vascular dementia (VaD) compared with those who had not experienced a hypoglycemic event (hazard ratio [HR], 1.254; 95% confidence interval [CI], 1.166 to 1.349; P<0.001 for all-cause dementia; HR, 1.264; 95% CI, 1.162 to 1.375; P<0.001 for AD; HR, 1.286; 95% CI, 1.110 to 1.490; P<0.001 for VaD). According to number of hypoglycemic episodes, the HRs of dementia were 1.170, 1.201, and 1.358 in patients with one hypoglycemic episode, two or three episodes, and more than three episodes, respectively. In the subgroup analysis, hypoglycemia was associated with an increased risk for dementia in both sexes with or without T2DM microvascular or macrovascular complications.CONCLUSION: Our findings suggest that patients with a history of hypoglycemia have a higher risk for dementia. This trend was similar for AD and VaD, the two most important subtypes of dementia.
Subject(s)
Humans , Cohort Studies , Dementia , Dementia, Vascular , Diabetes Mellitus, Type 2 , Hypoglycemia , Korea , National Health Programs , Propensity ScoreABSTRACT
The purpose of this study was to verify whether Mediterranean diet, which proved to have a significant effect on preventing dementia for people aged 65 or older, could be well modified to be a Korean-style Mediterranean diet. This study was performed as a randomized-controlled trial for 6 weeks. Functional physical changes, cognitive scores, depression scores and dietary changes were all assessed. The walking speed (P<0.001) and the cognitive scores were statistically improved in only the experimental group (P<0.001), and the depression scores were also significantly improved in only the experimental group (P<0.01). The dietary intake showed a 30% improvement for consuming more than 7 cups per day of vegetables and fruits. When the participants were contacted four months after the end of the study, 90% of them said that the Korean-style Mediterranean diet was feasible and 100% said the nutrition interventions helped them maintain the diet during their daily lives. The results suggest that although the Mediterranean diet can be difficult to apply, any limitations of this healthy diet can be overcome.
Subject(s)
Aged , Humans , Dementia , Depression , Diet , Diet, Mediterranean , Fruit , Vegetables , WalkingABSTRACT
BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) could be misleading in idiopathic normal-pressure hydrocephalus (iNPH). We therefore investigated the CSF biomarkers in 18F-florbetaben amyloid-negative positron-emission tomography (PET) [amyloid PET(−)] iNPH, amyloid-positive PET [amyloid PET(+)] AD, and cognitively normal (CN) subjects. METHODS: Ten amyloid PET(+) AD patients (56.7±5.6 years old, mean±standard deviation), 10 amyloid PET(−) iNPH patients (72.8±4.5 years old), and 8 CN subjects (61.2±6.5 years old) were included. We measured the levels of β-amyloid (Aβ)40, Aβ42, total tau (t-tau) protein, and phosphorylated tau (p-tau) protein in the CSF using enzyme-linked immunosorbent assays. RESULTS: The level of Aβ42 and the Aβ42/Aβ40 ratio in the CSF were significantly lower in AD than in iNPH or CN subjects. The Aβ40 level did not differ significantly between AD and iNPH (p=1.000), but it did between AD and CN subjects (p=0.032). The levels of both t-tau and p-tau were higher in AD than in iNPH or CN subjects. The levels of Aβ42, Aβ40, t-tau, and p-tau were lower in iNPH than in CN subjects, but there was no significant difference after controlling for age. CONCLUSIONS: Our results suggest that the mechanism underlying low CSF Aβ levels differs between amyloid PET(−) iNPH and amyloid PET(+) AD subjects. The lower levels of all CSF biomarkers in iNPH patients might be due to reduced clearances from extracellular fluid and decreased brain metabolism of the periventricular zone in iNPH resulting from glymphatic dysfunction.
Subject(s)
Humans , Alzheimer Disease , Amyloid , Biomarkers , Brain , Cerebrospinal Fluid , Enzyme-Linked Immunosorbent Assay , Extracellular Fluid , Hydrocephalus , Metabolism , Positron-Emission TomographyABSTRACT
BACKGROUND AND PURPOSE: We aimed to elucidate independent predictors of adverse outcomes in caregivers of patients with dementia using readily available clinical and demographic data of patients with dementia and their caregivers. METHODS: We reviewed patient-caregiver data from the Clinical Research Center for Dementia of South Korea and Caregivers of Alzheimer Disease Research study. The clinical factors of the patients and the demographics of both patients and caregivers were used to predict adverse outcomes for caregivers. Correlation and linear regression analyses were performed. RESULTS: We enrolled 454 patients and their caregivers for the present study. The general burden for the caregiver was higher amongst female caregivers, patients with further decreased the level of activities of daily living (ADL), patients with more abnormal behavior, or younger patients. The time spent by the caregivers was more in cases of patients with higher Caregiver Administered Neuropsychiatric Inventory scores, younger patients and for patients with decreased level of ADL. Depression amongst caregivers was more prominent in patients with higher Clinical Dementia Rating Sum of Boxes scores. Physical health-related quality of life (HRQoL) was lower in female caregivers, more physically affected patients, and older caregivers. Lastly, mental HRQoL was lower in younger, more physically affected, and in patients with abnormal behaviors. CONCLUSIONS: Clinical and demographic characteristics of patients and caregivers predict adverse outcomes for caregivers. Therefore, these factors should be considered to provide support to both patients and their caregivers.
Subject(s)
Female , Humans , Activities of Daily Living , Alzheimer Disease , Caregivers , Dementia , Demography , Depression , Korea , Linear Models , Quality of LifeABSTRACT
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: We investigated predictors of institutionalization in patients with Alzheimer's disease (AD) in South Korea. METHODS: In total, 2,470 patients with AD aged 74.5±7.8 years (mean±standard deviation, 68.1% females) were enrolled from November 2005 to December 2013. The dates of institutionalization were identified from the public Long-Term-Care Insurance program in January 2014. We used a Cox proportional-hazards model to identify predictors for future institutionalization among characteristics at the time of diagnosis in 2,470 AD patients. A similar Cox proportional-hazards model was also used to investigate predictors among variables that reflected longitudinal changes in clinical variables before institutionalization in 816 patients who underwent follow-up testing. RESULTS: A lower Mini Mental State Examination score [hazard ratio (HR)=0.95, 95% confidence interval (CI)=0.92–0.97] and higher scores for the Clinical Dementia Rating and Neuro-Psychiatric Inventory (HR=1.01, 95% CI=1.00–1.01) at baseline were independent predictors of institutionalization. The relationship of patients with their main caregivers, presence of the apolipoprotein E e4 allele, and medication at baseline were not significantly associated with the rate of institutionalization. In models with variables that exhibited longitudinal changes, larger annual change in Clinical Dementia Rating Sum of Boxes score (HR=1.15, 95% CI=1.06–1.23) and higher medication possession ratio of antipsychotics (HR=1.89, 95% CI=1.20–2.97) predicted earlier institutionalization. CONCLUSIONS: This study shows that among Korean patients with AD, lower cognitive ability, higher dementia severity, more-severe behavioral symptoms at baseline, more-rapid decline in dementia severity, and more-frequent use of antipsychotics are independent predictors of earlier institutionalization.
Subject(s)
Humans , Alleles , Alzheimer Disease , Antipsychotic Agents , Apolipoproteins , Behavioral Symptoms , Caregivers , Dementia , Diagnosis , Follow-Up Studies , Institutionalization , Insurance , KoreaABSTRACT
PURPOSE: Assessment of the severity and clinical course of asthma is important for effective disease control. Cognitive and physical impairments occur due to the aging process, which may impact on asthma control. We aimed to evaluate the impact of cognitive function on the assessment of asthma control in older asthmatics as a prospective interventional trial. METHODS: A total of 50 mild to moderate asthmatics over 60 years of age were enrolled. Three questionnaires were used: the asthma control test (ACT), the asthma-specific quality of life, and the Korean version of the Short Form of the Geriatric Depression Scale. The Seoul neuropsychological screening battery-dementia version (SNSB-D), Korean version of the Mini-Mental Status Examination, and the Seoul instrumental activities of daily living scale were applied for neuropsychological assessment. RESULTS: The mean patient age was 67.0±4.9 years, and 30 patients (60.0%) were female. The sensitivity and specificity of the ACT for determining well-controlled asthma were 91.7% and 39.5%, respectively. Regarding neuropsychological assessment, 22 patients (44%) had mild cognitive impairment, 4 (8.7%) had dementia, and 17 (34%) had depression. Total SNSB-D score was significantly higher in patients with an ACT score of ≥20 (P=0.015). The ACT scores were significantly associated with SNSB-D results in analyses adjusted for age, sex, education duration, lung function, and depression (P=0.004). CONCLUSION: We found significant positive correlations between cognitive functions, as measured by SNSB-D, and asthma control status, as measured by ACT scores, in older patients with asthma. Therefore, cognitive impairment may be associated with poor asthma control in older asthmatics.
Subject(s)
Female , Humans , Activities of Daily Living , Aging , Asthma , Cognition , Cognition Disorders , Dementia , Depression , Education , Lung , Mass Screening , Cognitive Dysfunction , Prospective Studies , Quality of Life , Sensitivity and Specificity , SeoulABSTRACT
Sustained downgaze mostly occurs in association with lesions affecting the dorsal midbrain. We report sustained downgaze in a patient with hepatic encephalopathy. The sustained downgaze existed for seven more days after she regained her consciousness. The persistent downgaze even after regaining full consciousness indicates localized pretectal dysfunction rather than diffuse encephalopathy as the mechanism of sustained downgaze in our patient. The ocular motor dysfunction in hepatic encephalopathy may be due to localized dysfunction of the brainstem
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A 64-year-old woman presented with headache and visual disturbance which occurred 10 minutes after bee venom acupuncture. She was normotensive. Her pupils were isocoric and normally reflexive but she could precept only lights just in front of her eyes. The brain MRI showed vasogenic edema in the cerebellum and occipitotemporoparietal areas. She fully recovered 2 days later. The brain MRI taken after 7 days revealed remarkable improvement. This case suggests that bee venom might cause posterior reversible encephalopathy syndrome.
Subject(s)
Female , Humans , Middle Aged , Acupuncture , Bee Venoms , Brain , Cerebellum , Edema , Headache , Magnetic Resonance Imaging , Posterior Leukoencephalopathy Syndrome , Pupil , ReflexABSTRACT
Distal hereditary motor neuropathy (dHMN) is a heterogeneous group of disorders characterized by weakness and wasting of distal limb muscles without overt sensory abnormalities. Recently, autosomal dominant dHMN has been mapped to chromosome 12q24 and 7q11-q21. We present a family with autosomal dominant adult onset dHMN type II consisting of fi ve affected individuals spanning three generations. They developed mild symmetrical distal lower limb weakness, muscle wasting, and severe foot deformity after the third decade. Genetic analysis showed no support for linkage to chromosome 12q24 and 7q11-q21 in our family. These fi ndings further demonstrate a genetic heterogeneity within dHMN type II.
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We report a man who presented with progressive disinhibition and through clinicoradiologic correlation using magnetic resonance imaging (MRI), aim to investigate the pathomechanism of disinhibition in neuro-Behcet's disease (NBD). A 46-year-old man presented with progressive disinhibition and apathy for 4 months. One month after his visit, additionally, he developed left partial third nerve palsy. His brain MRI showed lesions in the ventral caudate nucleus as well as left midbrain and thalamus. Taking his recurrent oral ulcers, uveitis, and erythema nodosum into consideration, he was diagnosed with NBD. We found that progressive disinhibition could be one of presenting symptoms in BD and might be associated with the caudate nucleus. This finding suggests that involvement of the basal ganglia in BD prior to the involvement of the brainstem could result in unique clinical features such as behavioral changes without extrapyramidal signs.
Subject(s)
Humans , Middle Aged , Apathy , Basal Ganglia , Brain , Brain Stem , Caudate Nucleus , Erythema Nodosum , Magnetic Resonance Imaging , Mesencephalon , Oculomotor Nerve Diseases , Oral Ulcer , Thalamus , UveitisABSTRACT
We report a man who presented with progressive disinhibition and through clinicoradiologic correlation using magnetic resonance imaging (MRI), aim to investigate the pathomechanism of disinhibition in neuro-Behcet's disease (NBD). A 46-year-old man presented with progressive disinhibition and apathy for 4 months. One month after his visit, additionally, he developed left partial third nerve palsy. His brain MRI showed lesions in the ventral caudate nucleus as well as left midbrain and thalamus. Taking his recurrent oral ulcers, uveitis, and erythema nodosum into consideration, he was diagnosed with NBD. We found that progressive disinhibition could be one of presenting symptoms in BD and might be associated with the caudate nucleus. This finding suggests that involvement of the basal ganglia in BD prior to the involvement of the brainstem could result in unique clinical features such as behavioral changes without extrapyramidal signs.