ABSTRACT
As modern society ages rapidly, the number of people with dementia is sharply increasing. Direct medical costs and indirect social costs for dementia patients are also increasing exponentially. However, the lack of social awareness about dementia results in difficulties to dementia patients and their families. So, understanding dementia is the first step to remove or reduce the stigma of dementia patients and promote the health of our community. Alzheimer's disease is the most common form of dementia. The term, ‘Alzheimer's disease’ has been used for over 100 years since first used in 1910. With the remarkable growth of science and medical technologies, the techniques for diagnosis and treatment of dementia have also improved. Although the effects of the current symptomatic therapy are still limited, dramatic improvement is expected in the future through the continued research on disease modifying strategies at the earlier stage of disease. It is important to look at the past to understand the present and obtain an insight into the future. In this article, we review the etymology and history of dementia and previous modes of recognizing dementia. We also review the historical developments leading to the terminology of Alzheimer's disease.
Subject(s)
Humans , Alzheimer Disease , Dementia , Diagnosis , Terminology as TopicABSTRACT
BACKGROUND AND PURPOSE: The one-day rivastigmine patch is reportedly well tolerated and has minimal side effects. However, Asian patients show more side effects than those in Western countries. We evaluated tolerability of the rivastigmine patch in South Korean patients with Alzheimer's disease (AD) and the specific factors affecting adverse events of the skin. METHODS: A 6-month, open labeled, multi-centered, observational study was carried out in 440 patients with probable AD from July 2009 to September 2010 (NCT01312363). RESULTS: A total of 25.9% of the patients experienced adverse skin events at the rivastigmine patch application site and 17.0% discontinued treatment due to adverse events at the skin application site. The most common adverse events were itching and erythema. Patients with an allergic history and users of electric heating appliances reported skin discomfort. Older age was associated with discontinuing treatment. CONCLUSION: These results suggest that the rivastigmine patch induced some adverse skin events and may contribute to understanding and improving skin tolerability to the rivastigmine patch.
Subject(s)
Humans , Alzheimer Disease , Asian People , Erythema , Heating , Hot Temperature , Observational Study , Pruritus , Skin , RivastigmineABSTRACT
Marchiafava-Bignami disease (MBD) is a rare disorder of demyelination or necrosis of the corpus callosum. Mainly, MBD is associated with alcohol and malnutrition. We report a 60-year-old woman with no history of alcohol consumption or malnutrition who had MBD as a possible complication of normal pressure hydrocephalus (NPH). The patient presented with a 2-month history of progressive gait unsteadiness, urinary incontinence, and forgetfulness, for which the patient underwent ventriculoperitoneal shunt surgery with remarkable improvement. Magnetic resonance imaging (MRI) demonstrated hyperintensity in the body and splenium of corpus callosum when she was brought to the hospital again with rapid deterioration of her mental ststus. It might be postulated that cerebrospinal fluid (CSF) tumor necrosis factor-alpha (TNF-alpha) might have contributed to the development of MBD although not measured in this patient, given that TNF-alpha, as a proinflammatory cytokine mediating demyelinating process have been found in be increased in the CSF of NPH.
Subject(s)
Female , Humans , Middle Aged , Alcohol Drinking , Cerebrospinal Fluid , Corpus Callosum , Demyelinating Diseases , Gait , Hydrocephalus, Normal Pressure , Magnetic Resonance Imaging , Malnutrition , Marchiafava-Bignami Disease , Necrosis , Negotiating , Tumor Necrosis Factor-alpha , Urinary Incontinence , Ventriculoperitoneal ShuntABSTRACT
STUDY DESIGN: A case report. OBJECTIVE: We present a rare case of acute spinal cord infarction and usefulness of diffusion weighted MR imaging. SUMMARY OF LITERATURE REVIEW: T1-weighted and T2-weighted images are often normal in a patient with acute spinal cord infarction. MATERIAL AND METHODS: An 82-year-old presented with acute onset of paraplegia and urinary retention. His symptoms developed 6 days ago without any trauma. He had a history of vertebroplasty due to compression fracture of 12th thoracic vertebral body 6 years ago. There was no evidence of spinal cord compression on routine T1-and T2-weighted MRI. RESULTS: In diffusion-weighted MRI, a high intensity signal intensity lesion in the spinal cord and conus medullaris was observed. CONCLUSION: We report an example for the usefulness of diffusion-weighted image for early and accurate diagnosis of acute spinal cord infarction.
Subject(s)
Humans , Conus Snail , Diffusion , Fractures, Compression , Infarction , Paraplegia , Spinal Cord , Spinal Cord Compression , Urinary Retention , VertebroplastyABSTRACT
Activities of daily living (ADL) refer to the ability to care for self and perform daily activities within an individual's place or in outdoor environments. ADL comprise two main categories: Basic or physical ADL and Instrumental ADL. The latter allows for the earlier detection of functional decline than the former. The cognitive changes in neurodegenerative dementias contribute to the impaired ability of the patients to take care of themselves. Activities of daily living is a major criterion for diagnosing dementia. Furthermore, it has recently been emphasized that some impairment of activities of daily living, particularly of complex instrumental functions, is already present even in mild cognitive impairment prodromal stage of dementia, although mild cognitive impairment is distinguished from dementia by the absence of significant deficit in activities of daily living. The impaired activities of daily living increase the rate of institutionalization of the patients with dementia to nursing home and inevitably bring about the changes in the qualities of life not only of the patients but their caregivers. One of the best ways to evaluate the degree of impairment in activities of daily living and the care burden is through standardized functional assessment tools according to the severity of dementia. These tools provide objective data, thereby allowing the clinicians to judge decline and improvement in the functional status and to plan individualized care. In this review, we will review the clinical significance of evaluating ADL, the assessment tools according to the severity of dementia, and therapeutic approaches to enhance the functional levels. We will also review the impact of the impaired ADL on the quality of life among the patients and their care providers.
Subject(s)
Humans , Activities of Daily Living , Caregivers , Dementia , Hypogonadism , Institutionalization , Cognitive Dysfunction , Mitochondrial Diseases , Nursing Homes , Ophthalmoplegia , Prodromal Symptoms , Quality of LifeABSTRACT
During recent years, there has been remarkable progress with respect to the identification of molecular mechanisms and underlying pathology of neurodegenerative dementias. The latest evidence indicates that a common cause and pathological mechanism of diverse neurodegenerative dementias can be found in the increased production, misfolding, aggregation, and accumulation of specific proteins such as beta-amyloid, tau protein, alpha-synuclein, prion protein, polyglutamine, transactive response DNA-binding protein (TARDBP or TDP-43), or fused in sarcoma (FUS). The conformational variants of these proteins range from small oligomers to the characteristic pathologic inclusions. However, it is noteworthy that a certain pathology can be a hallmark of a certain dementia, but there is a substantial overlap between different pathologies and different types of dementias. In this review, molecular mechanisms and pathologies of different neurodegenerative dementias will be summarized from the perspective of proteins rather than from the viewpoint of individual dementias. We will also review recent evidence surrounding these protein misfolding disorders, the role of toxic oligomers, cell-to-cell transmission, and the links between the misfolded proteins, along with the general therapeutic strategies for the protein misfolding disorders.
Subject(s)
alpha-Synuclein , Dementia , Neurodegenerative Diseases , Peptides , Proteins , Proteostasis Deficiencies , Sarcoma , tau ProteinsABSTRACT
BACKGROUND: Episodic memory impairment can be subdivided into two subtypes, encoding failure vs. retrieval deficit. We defined two subtypes of amnestic mild cognitive impairment (aMCI) according to recognition performance on the memory test: aMCI with encoding failure or aMCI-E and aMCI with retrieval deficit or aMCI-R. We hypothesized that compared to aMCI-R, subjects with aMCI-E are more likely to convert to Alzheimer's disease, as encoding failure suggests that medial temporal lobes are affected early in the disease process. We also investigated whether aMCI-E can be a predictor for progression to AD. METHODS: Using the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, a total of 397 aMCI subjects were included. APOE genotype, cerebrospinal fluid (CSF) fluid biomarkers, and a set of neuropsychological measures were also collected. Unadjusted and adjusted odds ratios were calculated to predict the conversion to AD dementia. The Spearman's rs test was used to measure the degree of correlation between aMCI subtypes and the prognostic factors for progression to AD. RESULTS: Among the 397 subjects, 209 (52.6%) subjects were classified into aMCI-E and 188 (47.4%) into aMCI-R. One hundred two (48.8%) subjects with aMCI-E and 57 (30.3%) of those with aMCI-R progressed to AD (unadjusted odds ratio=2.19 with 95% confidence interval [CI] 1.45-3.31) over 3 years. However, when adjusted odds ratio by a logistic regression was calculated, probability value of aMCI-E disappeared with the odds of conversion by of 1.47 (95% CI 0.89-2.43). There were statistically significant correlations between aMCI-E subtype and MMSE, CDR Memory, RAVLT delayed recall, CSF biomarkers, and genotypes. CONCLUSIONS: This analysis did not show that aMCI-E is an independent prognostic factor to predict the progression to AD. However, this subtype significantly correlates with other prognostic factors for progression. This may suggest that aMCI-E might be a later stage of aMCI and aMCI-R an earlier stage which might be a better target than aMCI-E for therapeutic intervention. Further studies are needed to validate this conjecture.
Subject(s)
Alzheimer Disease , Apolipoproteins E , Biomarkers , Dementia , Deoxycytidine , Disease Progression , Genotype , Logistic Models , Memory , Memory, Episodic , Cognitive Dysfunction , Neuroimaging , Odds Ratio , Temporal LobeABSTRACT
The majority of neurodegenerative dementias are thought to result primarily from the misfolding, aggregation and accumulation of proteins which interfere with protein homeostasis in the brain. Some of them are caused by the expansion of unstable nucleotide repeats, which include Huntington's disease as a prototype. Other neurodevelopmental or neurodegenerative disorders, such as fragile X syndrome, some spinocerebellar ataxias and myotonic dystrophies exhibit cognitive or behavioral deficits as parts of their clinical manifestations. Unstable repeat expansions include trinucleotide, tetranucleotide, and pentanucleotide. Recently hexanucleotide repeat expansion in frontotemporal dementia and amyotrophic lateral sclerosis was identified. The pathogenic mechanisms for these repeat disorders include either loss of protein function or gain of function at the protein or RNA levels. The aim of this article is to review proposed mechanisms by which unstable repeat expansions give rise to degeneration of brain with the hope of understanding the diseases and providing insights into the areas of therapeutic intervention. We will review these potential mechanisms in the context of fragile X syndrome, Huntington's disease, spinocerebellar ataxias, myotonic dystrophy, and frontotemporal dementia and amyotrophic lateral sclerosis. We will also discuss the potential targets for therapeutic intervention.
Subject(s)
Amyotrophic Lateral Sclerosis , Brain , Dementia , Fragile X Syndrome , Frontotemporal Dementia , Homeostasis , Huntington Disease , Myotonic Dystrophy , Neurodegenerative Diseases , Proteins , RNA , Spinocerebellar AtaxiasABSTRACT
The majority of neurodegenerative dementias are thought to result primarily from the misfolding, aggregation and accumulation of proteins which interfere with protein homeostasis in the brain. Some of them are caused by the expansion of unstable nucleotide repeats, which include Huntington's disease as a prototype. Other neurodevelopmental or neurodegenerative disorders, such as fragile X syndrome, some spinocerebellar ataxias and myotonic dystrophies exhibit cognitive or behavioral deficits as parts of their clinical manifestations. Unstable repeat expansions include trinucleotide, tetranucleotide, and pentanucleotide. Recently hexanucleotide repeat expansion in frontotemporal dementia and amyotrophic lateral sclerosis was identified. The pathogenic mechanisms for these repeat disorders include either loss of protein function or gain of function at the protein or RNA levels. The aim of this article is to review proposed mechanisms by which unstable repeat expansions give rise to degeneration of brain with the hope of understanding the diseases and providing insights into the areas of therapeutic intervention. We will review these potential mechanisms in the context of fragile X syndrome, Huntington's disease, spinocerebellar ataxias, myotonic dystrophy, and frontotemporal dementia and amyotrophic lateral sclerosis. We will also discuss the potential targets for therapeutic intervention.
Subject(s)
Amyotrophic Lateral Sclerosis , Brain , Dementia , Fragile X Syndrome , Frontotemporal Dementia , Homeostasis , Huntington Disease , Myotonic Dystrophy , Neurodegenerative Diseases , Proteins , RNA , Spinocerebellar AtaxiasABSTRACT
BACKGROUND: The main complication of cerebral cavernous angioma is hemorrhage. Ischemic stroke as a complication of cerebral cavernous angioma has rarely been described, and hemorrhage after ischemic Wallenberg's syndrome has not been reported before. CASE REPORT: A 45-year-old woman presented with perioral numbness, hoarseness, dysphagia, and worsening of her previous sensory symptoms. The patient had been taking aspirin for 3 years after suffering from ischemic Wallenberg's syndrome with left paresthesia as a residual symptom. Brain computed tomography revealed an acute medullary hematoma in the previously infarcted area. Follow-up magnetic resonance imaging revealed a cavernous angioma in the right medulla. CONCLUSIONS: We presume that cerebral cavernous angioma was responsible for both the ischemia and the hemorrhage, and we also cautiously speculate that the aspirin contributed to the development of hemorrhage in the previously infarcted area.
Subject(s)
Female , Humans , Middle Aged , Aspirin , Brain , Caves , Deglutition Disorders , Follow-Up Studies , Hemangioma, Cavernous , Hematoma , Hemorrhage , Hoarseness , Hypesthesia , Ischemia , Lateral Medullary Syndrome , Magnetic Resonance Imaging , Medulla Oblongata , Paresthesia , Stress, Psychological , StrokeABSTRACT
The accumulation of beta-amyloid (A beta) aggregates is a characteristic of Alzheimer's disease (AD). Furthermore, these aggregates have neurotoxic effects on cells, and thus, molecules that inhibit A beta aggregate formation could be valuable therapeutics for AD. It is well known that aggregation of A beta depends on its hydrophobicity, and thus, in order to increase the hydrophilicity of A beta, we considered using citrate, an anionic surfactant with three carboxylic acid groups. We hypothesized that citrate could reduce hydrophobicity and increase hydrophilicity of A beta(1-40) molecules via hydrophilic/electrostatic interactions. We found that citrate significantly inhibited A beta(1-40) aggregation and significantly protected SH-SY5Y cell line against A beta(1-40) aggregates-induced neurotoxicity. In details, we examined the effects of citrate on A beta(1-40) aggregation and on A beta(1-40) aggregates-induced cytotoxicity, cell viability, and apoptosis. Th-T assays showed that citrate significantly inhibited A beta(1-40) aggregation in a concentration-dependent manner (Th-T intensity: from 91.3% in 0.01 mM citrate to 82.1% in 1.0 mM citrate vs. 100.0% in A beta(1-40) alone). In cytotoxicity and viability assays, citrate reduced the toxicity of A beta(1-40) in a concentration-dependent manner, in which the cytotoxicity decreased from 107.5 to 102.3% as compared with A beta(1-40) aggregates alone treated cells (127.3%) and the cell viability increased from 84.6 to 93.8% as compared with the A beta(1-40) aggregates alone treated cells (65.3%). Furthermore, Hoechst 33342 staining showed that citrate (1.0 mM) suppressed A beta(1-40) aggregates-induced apoptosis in the cells. This study suggests that citrate can inhibit A beta(1-40) aggregation and protect neurons from the apoptotic effects of A beta(1-40) aggregates. Accordingly, our findings suggest that citrate administration should be viewed as a novel neuroprotective strategy for AD.
