Mild Stage Of Disease Research Articles

Describing cognitive decline of patients at the mild or moderate stages of Alzheimer's disease using the Standardized MMSE.

To describe the progression of patients with mild or moderate Alzheimer's disease (AD) to a severe stage using the Standardized Mini-Mental State Examination (SMMSE). A cohort of 206 patients was stratified according to their baseline SMMSE scores: mild (19-24) and moderate (10-18). Proportional hazards analyses were used to determine the hazard of switching into a severe stage, defined as SMMSE score < 10. Among patients at the mild stage, 25% reached the severe stage within 2.6 years, and in the moderate group within 1.5 years. Patients with hallucinations at the mild stage experienced more rapid decline. The previous rate of decline was also found to be an important predictor. At the moderate stage, key predictors were lower SMMSE score and longer time since onset. Current SMMSE scores with other clinical details can be used to advise patients and caregivers about the expected progression of AD.

Cerebrospinal Fluid Amyloid β1–42 Levels in the Mild Cognitive Impairment Stage of Alzheimer's Disease

Cerebrospinal fluid (CSF) levels of amyloid β-protein ending at amino acid position 42 (CSF-A β1–42) and CSF-tau levels were quantified by sandwich ELISAs in 19 patients with mild cognitive impairment (MCI) who eventually developed Alzheimer's disease (AD) on follow-up as well as in 15 age-matched normal controls and 54 AD patients at diverse stages of the disease. In the present study, the annual conversion rate was approximately 15%. The CSF-A β1–42 levels did not differ significantly between the normal control group and the MCI group, however, these values declined significantly once AD became clinically overt. In contrast to CSF-Aβ1–42, CSF-tau levels were significantly increased in the MCI stage, and these values continued to be elevated thereafter, indicating that increased levels of CSF-tau may help in detecting MCI subjects who are predicted to develop AD. We propose that CSF-tau and CSF-A β1–42 must be used as two distinct biomarkers that should be applied appropriately in clinical settings.

Clinical characterization of patients with hereditary pancreatitis and mutations in the cationic trypsinogen gene

Purpose We determined the clinical manifestations of hereditary pancreatitis in nearly 30 families. Patients and methods The two trypsinogen mutations N29I and R122H were identified in a group of 550 patients with chronic pancreatitis of unclear origin. The following criteria were used to characterize the severity of chronic pancreatitis (one point each): calcifications, cysts, dilation of the pancreatic duct, diabetes, hospital treatment, and operation. Stages were defined as stage 0 (no points), stage 1 (one to two points), stage 2 (three to four points), and stage 3 (more than four points). Smoking and drinking habits were also recorded. Results Six families with the N29I mutation (25 subjects with the mutation) and 21 families with the R122H mutation (76 subjects with the mutation) were identified. The median ages for the onset of disease were 11 years in N29I and 10 years in R122H patients. The severity of chronic pancreatitis and symptoms were similar for both mutations. About 26% (n = 26) of the 101 subjects carrying a mutation were asymptomatic, and 42% (n = 42) had mild disease (stage 1). Twenty-nine percent (n = 29) had moderate disease (stage 2), and only 4% (n = 4) had severe disease (stage 3). Conclusions Symptoms of patients with the N29I or R122H trypsinogen mutation were generally similar. The majority of subjects with trypsinogen mutations had mild disease or was asymptomatic.

Temporal lobe asymmetry in patients with Alzheimer's disease with delusions

OBJECTIVETo test the hypothesis that delusions are associated with asymmetric involvement of the temporal lobe regions in Alzheimer's disease.METHODSTemporal lobe atrophy was assessed with a linear measure of width of...

Economic burden of amyotrophic lateral sclerosis in the United Kingdom

To assess the economic burden of amyotrophic lateral sclerosis (ALS) in the United Kingdom, yearly direct medical costs were determined for four defined ALS health states (mild, moderate, severe and terminal disease stages). Resource utilisation patterns for each health state were obtained from United Kingdom neurologists and local costs (1996/97) were attached to the resources. The annual direct cost of the health states increased from £1185.20 in mild disease to £3127.51 in the terminal state. Hospitalisation was a major contributor to total cost in mild (43.3%), severe (31.6%) and terminal (45.1%) states. In contrast, in moderate disease the impact of hospitalisation was minimal (0.8%) compared to physician remuneration costs (59%). The economic burden of ALS is therefore directly related to the severity of the disease. The study identifies the major cost drivers in current ALS care and provides a means for determining how potential therapeutic interventions might affect the overall cost of the disease.

Adult day care centers and the treatment of Alzheimer's disease patients: A critical analysis

Increasingly adult day care services will provide transitional care for Alzheimer's disease patients in mild or moderate stages of the disease. The following small scale studyfinds that adult day care services as transitional care allows patients with Alzheimer's disease to remain in the community for a longer period of care, than would otherwise be possible. The quality of life of patients appears to be highest in private (mostly voluntary) adult day care centers. The most comprehensive case management is found in private (voluntary and proprietary) adult day care centers rather than in public adult day care centers. Such private centers seem to have a more positive impact on behavioralfunctioning than the less comprehensive approach utilized by the public centers. Also, even where adult day care services are provided, informal caregivers are better able to function when they have an informal system of support offamily members and/or neighbors. In addition to adult day care service, family caregivers also need respite care and other supportive social services. Also, the study reveals some discrepancy between formal and informal caregiver perceptions of patient condition.

Attentional disengagement deficit in nondemented elderly over 75 years of age

Abstract Healthy older adults in the age range of 60-75 years are moderately deficient in visuospatial attention when central location cues are used to shift attention, but not when peripheral cues are used. In contrast, older adults with dementia of the Alzheimer's type (DAT) exhibit an attention shifting (disengagement) deficit for both central and peripheral cues. If the effects of dementia and normal aging on visuospatial attention differ qualitatively, then peripherally cued shifts of attention should be unaffected even in very old nondemented persons. to examine this possibility, subjects in six age groups (17-24, 35-44, 45-54, 55-64, 65-74, and 75-85 years) were tested on a visuospatial attention task. Valid, invalid and neutral location cues preceded a letter target requiring, in separate conditions, either speeded detection or discrimination. Combined costs and benefits of cue validity on reaction time (RT) increased with age in the discrimination but not in the detection task. the oldest group (75-85) showed significantly larger RT costs and benefits than the next oldest group (65-74), for both central and peripheral cues. the 75-85 year-olds were significantly slower than the 65-75 year-olds on invalid trials (costs) but not on valid trials (benefits), pointing to a disengagement deficit, as reported previously for patients with either parietal lobe damage or DAT. the results suggest that in healthy nondemented subjects of advanced age (over 75 years), visuospatial attention is affected similarly to younger patients in the early, mild stages of Alzheimer's disease.

Multicenter Study of Predictors of Disease Course in Alzheimer Disease (the “Predictors Study”). I. Study Design, Cohort Description, and Intersite Comparisons

Clinicians should be able to provide the patient with Alzheimer disease (AD) and the family with an accurate prediction of what to expect, but the variability in the rate of disease progression precludes this. In several previous studies, specific clinical signs such as muscular rigidity, myoclonus, and hallucinations or delusions were associated with rapid progression to a more severe stage of dementia or death. The "Predictors Study," a longitudinal study at three independent sites, was designed to develop a predictor model of the natural history of Alzheimer disease. The study was conducted at three study sites, New York, Baltimore, and Boston in a cohort of 224 patients with early probable AD. This article describes the design and implementation of the Predictors Study, and compares features of the study cohort at baseline across sites. Patients were all at the mild stage of disease at entry and were relatively comparable across sites. Extrapyramidal signs and delusions were common, but myoclonus was rarely observed.

Definitions in Chronic Obstructive Pulmonary Disease

States of airflow obstruction are common disorders which span the spectrum from asthmatic-chronic bronchitis to emphysema. Asthmatic and chronic bronchitic states are at least potentially reversible by systematic, pharmacologically oriented therapy focusing on bronchodilators and corticosteroids. Both asthmatic bronchitis, particularly when it is not adequately treated, and emphysema result in the final common pathway of COPD. These are generally progressive states, unless smoking cessation can be achieved in early or mild stages of disease. The future focuses on the great challenge of early identification, classification, and intervention. Thus, all patients with cough, dyspnea, and wheeze should be carefully evaluated by health workers who understand the history, physical examination, and simple pulmonary function tests in the context of chest radiology. These clinical methods together can help define the disease states characterized by airflow obstruction. Often, a final definition of disease cannot be made until aggressive attempts at the treatment of the airflow obstruction and its attendant symptoms complex have been vigorously pursued by experienced clinicians.

Ultrastructural findings in horses with chronic obstructive pulmonary disease (COPD) II: pathomorphological changes of the terminal airways and the alveolar region

Extensive light and electron microscope studies (transmission and scanning electron microscopy) of the bronchioles and alveolar region, in 28 horses suffering chronic obstructive pulmonary disease (COPD) and eight control horses, revealed good correlation between clinical severity and morphological changes. In the bronchiolar epithelium the non-ciliated bronchiolar epithelial (Clara) cells, in particular, showed ultrastructural alterations and, even in the mild stages of disease, these presented degenerative changes and lack of differentiation. Together with loss of granulation in the Clara cells and metaplasia of the goblet cells, cells were seen with unusual intracytoplasmic lamellar inclusion, the number of which increased sharply with clinical severity. The focal changes in the alveolar region were necrosis of type I epithelial cells, alveolar fibrosis of varying degrees with type II epithelial transformation and emphysema or hyperinflation, with an increase in Kohn's pores. Some horse also showed morphological signs of interference with the surfactant system, in the form of marked cysts with lamellar structure. The alveolar changes were mostly in the peribronchiolar region and were, therefore, interpreted as reactive processes. No conclusions as to the aetiology of equine COPD can be derived from these morphological investigations.

Electrodermal characteristics in psychosomatic patient groups

Specific autonomic reaction patterns in different psychosomatic patient groups have been by several authors. In our study 50 male hypertensive patients and 47 male duodenal ulcer patients both in the early mild reversible stage of disease were compared with 65 male control persons to determine distinguishing features of electrodermal activity in response to a sequence of verbal, acoustic and colour stimuli. The two patient groups show opposite characteristics in respect to the initial skin resistance level, response amplitude and non-specific responses. Slower recovery can be seen only in an emotionally disturbing situation in the duodenal ulcer group. On the contrary, in orienting situations the control persons tend to show slower electrodermal recovery. According to the results of factor analysis, the components of electrodermal activity belong to 3 different factors, underlining the relative independence of these parameters. The first factor contains the electrodermal amplitude values. The temporal characteristics of electrodermal responses belong to two different factors, the first being in connection with the orienting situation and the second with the emotionally disturbing situation. The longer recovery in orienting situations is associated positively with facilitating achievement anxiety and negatively with debilitating achievement anxiety. The anxiety and neurosis scores belong to the third factor in connection with the prolonged electrodermal responses in emotionally disturbing situations. Anxiety and depression scores are higher in both patient groups, in accordance with the results of earlier studies. The parameters of electrodermal responses were analyzed as a function of psychological characteristics.

Differing Populations of Mitochondria Isolated from the Skeletal Muscle of Normal and Dystrophic Hamsters

Polarographic studies of a magnesium-responsive, calcium-associated defect of oxidative phosphorylation in dystrophic hamster skeletal muscle suggested that all dystrophic mitochondria are defective. This is at variance with the typical histological picture of dystrophic muscle, which shows, besides defective muscle fibers, many apparently normal cells, with presumably normal mitochondria. This discrepancy was resolved by linear sucrose density-gradient centrifugation (39–51%, w/v), which can separate normal mitochondria from calcium-loaded organelles. Upon density-gradient centrifugation of control and dystrophic muscle mitochondria, both preparations were found to yield suspended bands of similar density. However, the dystrophic preparations also produced a pellet at the bottom (most dense region) of the tube with calcium levels 10–40 times higher than those in the suspended bands. The data show the existence in dystrophic muscle of a distinct population of mitochondria with very high calcium levels that is absent from normal preparations. During the course of oxidative phosphorylation measurements, loss of calcium from these particular organelles and its uptake by others appear to render all the mitochondria defective. This exchange can be prevented by ruthenium red. Density-gradient centrifugation allows the identification of dystrophic muscle mitochondria in early and/or mild disease stages in which polarographic testing of mitochondria isolated by conventional centrifugation fails to detect an abnormality.