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At least 19 recordsLinked to original sources
PubMed2006

Preclinical pharmacokinetics and metabolism of 6-(4-(2,5-difluorophenyl)oxazol-5-yl)-3-isopropyl-[1,2,4]-triazolo[4,3-a]pyridine, a novel and selective p38alpha inhibitor: identification of an active metabolite in preclinical species and human liver microsomes.

The disposition of 6-(4-(2,5-difluorophenyl)oxazol-5-yl)-3-isopropyl-[1,2,4]-triazolo[4,3-a]pyridine (1), a potent and selective inhibitor of mitogen activated protein (MAP) kinase p38alpha, was characterized in several animal species in support of its selection for preclinical safety studies and potential clinical development. 1 demonstrated generally favorable pharmacokinetic properties in all species examined. Following intravenous (i.v.) administration, 1 exhibited low volumes of distribution at steady state (Vd(ss)) ranging from 0.4-1.3 l/kg (2.4-26 l/m(2)) in the rat, dog and monkey. Systemic plasma clearance was low in cynomolgus monkeys (6.00 ml/min/kg, 72.0 ml/min/m(2)) and Sprague-Dawley rats (7.65+/-1.08 ml/min/kg, 45.9+/-6.48 ml/min/m(2) in male rats and 3.15+/-0.27 ml/min/kg, 18.9+/-1.62 ml/min/m(2) in female rats) and moderate in beagle dogs (12.3+/-5.1 ml/min/kg, 246+/-102 ml/min/m(2)) resulting in plasma half-lives ranging from 1 to 5 h in preclinical species. Moderate to high bioavailability of 1 was observed in rats (30-65%), dogs (87%) and monkeys (40%) after oral (p.o.) dosing consistent with the in vitro absorption profile of 1 in the Caco-2 permeability assay. In rats, the oral pharmacokinetics were dose dependent over the dose range studied (5, 50 and 100 mg/kg). The principal route of clearance of 1 in rat, dog, monkey and human liver microsomes and in vivo in preclinical species involved oxidative metabolism mediated by cytochrome P450 enzymes. The major metabolic fate of 1 in preclinical species and humans involved hydroxylation on the isopropyl group to yield the tertiary alcohol metabolite 2. In human liver microsomes, this transformation was catalysed by CYP3A4 as judged from reaction phenotyping analysis using isozyme-specific inhibitors and recombinant CYP enzymes. Metabolite 2 was also shown to possess inhibitory potency against p38alpha in a variety of in vitro assays. 1 as well as the active metabolite 2 were moderately to highly bound to plasma proteins (f(u) approximately 0.1-0.33) in rat, mouse, dog, monkey and human. 1 as well as the active metabolite 2 did not exhibit competitive inhibition of the five major cytochrome P450 enzymes namely CYP1A2, 2C9, 2C19, 2D6 and 3A4 (IC(50)>50 microM). Overall, these results indicate that the absorption, distribution, metabolism and excretion (ADME) profile of 1 is relatively consistent across preclinical species and predict potentially favorable pharmacokinetic properties in humans, supporting its selection for toxicity/safety assessment studies and possible investigations in humans as an anti-inflammatory agent.

Administration, Oral↗
PubMed1980

Preclinical teachers and preclinical students.

A survey in 1974 in Manchester University medical school of the preclinical teachers showed that they thought that the motives of students in studying medicine were not what they should have been. Medically qualified and non-medically qualified teachers agreed about the importance of nine suggested motives, but there were highly significant differences between the two groups about the motives they felt to be present in students. The non-medically qualified were very much more likely to see students as concerned with the financial and social rewards of medicine, and more likely to doubt students' desires to be professionally competeant or to help individuals. Some anecdotal evidence possibly throws light on these findings, which may have serious implications for teaching as non-medically qualified staff make up an increasing proportion of preclinical teachers.

Attitude of Health Personnel↗
PubMed1995

Docetaxel (Taxotere): a review of preclinical and clinical experience. Part I: Preclinical experience.

Docetaxel is a taxoid which is currently in phase II/III clinical trials in Europe, the US and Japan. It was found to promote tubulin assembly in microtubules and to inhibit their depolymerization. In vitro, the docetaxel concentrations required to reduce murine and human cell survival by 50% ranged from 4 to 35 ng/ml and the cytotoxic effects were greater on proliferating than on non-proliferating cells. It was also found to be cytotoxic on fresh human tumor biopsies. In vivo, the drug was found to be schedule independent. A total of 13/14 murine transplantable tumors were found very sensitive to i.v. docetaxel and complete regressions of advanced stage tumors were obtained. Activity was also observed in 15/16 human tumor xenografts in nude mice at an advanced stage. In combination studies, synergism was observed in vivo with 5-fluorouracil, cyclophosphamide and etoposide. Pharmacokinetic evaluation revealed linear pharmacokinetics in tumor-bearing mice. There was a good tumor retention with a 22 h elimination half-life. Plasma protein binding ranged from 76 to 89%. Preclinical toxicology evaluation of docetaxel included single-dose toxicity in rats, mice and dogs, 5-day toxicity in mice and dogs, intermittent-dose toxicity in rats, dogs and monkeys, genetic and reproductive toxicity, as well as investigation of the irritation and sensitization potential. The principal toxicities were hematopoietic (all species), gastrointestinal (dog, monkey) and neuromotor (mice). Dogs appeared to be the most sensitive species. The clinical entry dose of 5 mg/m2 was based on one-third of the 'toxic dose low' in dogs (15 mg/m2).

Animals↗
PubMed2001

Use of preclinical data for selection of a phase II/III dose for evernimicin and identification of a preclinical MIC breakpoint.

One of the most challenging issues in the design of phase II/III clinical trials of antimicrobial agents is dose selection. The choice is often based on preclinical data from pharmacokinetic (PK) studies with animals and healthy volunteers but is rarely linked directly to the target organisms except by the MIC, an in vitro measure of antimicrobial activity with many limitations. It is the thesis of this paper that rational dose-selection decisions can be made on the basis of the pharmacodynamics (PDs) of the test agent predicted by a mathematical model which uses four data sets: (i) the distribution of MICs for clinical isolates, (ii) the distribution of the values of the PK parameters for the test drug in the population, (iii) the PD target(s) developed from animal models of infection, and (iv) the protein binding characteristics of the test drug. In performing this study with the new anti-infective agent evernimicin, we collected a large number (n = 4,543) of recent clinical isolates of gram-positive pathogens (Streptococcus pneumoniae, Enterococcus faecalis and Enterococcus faecium, and Staphylococcus aureus) and determined the MICs using E-test methods (AB Biodisk, Stockholm, Sweden) for susceptibility to evernimicin. Population PK data were collected from healthy volunteers (n = 40) and patients with hypoalbuminemia (n = 12), and the data were analyzed by using NPEM III. PD targets were developed with a neutropenic murine thigh infection model with three target pathogens: S. pneumoniae (n = 5), E. faecalis (n = 2), and S. aureus (n = 4). Drug exposure or the ratio of the area under the concentration-time curve/MIC (AUC/MIC) was found to be the best predictor of microbiological efficacy. There were three possible microbiological results: stasis of the initial inoculum at 24 h (10(7) CFU), log killing (pathogen dependent, ranging from 1 to 3 log(10)), or 90% maximal killing effect (90% E(max)). The levels of protein binding in humans and mice were similar. The PK and PD of 6 and 9 mg of evernimicin per kg of body weight were compared; the population values for the model parameters and population covariance matrix were used to generate five Monte Carlo simulations with 200 subjects each. The fractional probability of attaining the three PD targets was calculated for each dose and for each of the three pathogens. All differences in the fractional probability of attaining the target AUC/MIC in this PD model were significant. For S. pneumoniae, the probability of attaining all three PD targets was high for both doses. For S. aureus and enterococci, there were increasing differences between the 6- and 9-mg/kg evernimicin doses for reaching the 2 log killing (S. aureus), 1 log killing (enterococci), or 90% E(max) AUC/MIC targets. This same approach may also be used to set preliminary in vitro MIC breakpoints.

Aminoglycosides↗
PubMed1993

[Preclinical and clinical studies on a tumor marker, galactosyltransferase associated with tumor (GAT), in ovarian cancer (first report)--preclinical study of GAT assay kit and clinical study of normal level].

We conducted preclinical and clinical studies on GAT: Galactosyltransferase Associated with Tumor, a newly developed tumor marker of ovarian carcinoma. This paper presents the results of evaluation of a GAT assay kit, the normal range of its values, and analysis of its value relative to age, menstrual cycle, and stage of pregnancy. Calibration curve, reproducibility, analytical recovery test, and dilution test all yielded favorable results, and the assay system was proved to be reliable in both precision and reproducibility. However, special attention must be paid to highly hemolytic samples because of a positive error in GAT value for samples with a high concentration of hemoglobin. The cut-off value was set at 16U/ml based on the mean+2SD of healthy females. A uniform cut-off value could be employed since neither age nor stage of menstrual cycle had any observable influence on the level. The positive rate for healthy subjects was 3.1%, when the cut-off value of 16 U/ml was used. On the other hand, elevation of the GAT value was observed during the progression of pregnancy.

Adult↗
PubMed1998

[Preclinical blood gas analysis. 1. The value of preclinical blood gas analysis].

UNLABELLED: Prehospital blood gas analysis is a new method in out-of-hospital emergency care. In a prospective pilot study we evaluated the feasibility of prehospital compensation of severe acidosis relying on different monitoring systems to evaluate patients oxygen, carbon dioxide or acid-base status, respectively. METHODS: With the help of arterial blood gas checks taken at the site of the emergency, the acid base status of patients undergoing out of hospital cardiopulmonary resuscitation was analysed. The values derived from the first arterial puncture were used to determine the presence and the type of acidosis. The data of the arterial blood gas checks were set into relation with the time elapsed since the beginning of resuscitation and they were compared with end-tidal CO2. RESULTS: During the observation period 26 blood gas analyses from patients who had out-of-hospital resuscitation because of cardiac arrest were done. Twenty three patients had severe acidosis (pH range < 6.9 to 7.31), one had alkalosis (pH 7.51). Only two had an arterial pH within normal range. The pCO2 was variable (range: 24 to 97 mm Hg). The correlation of pH with time from the beginning of resuscitation to arterial puncture was poor (r = 0.407, p < 0.05). There was no correlation between pH and BE (r = 0.267) or pH and pCO2, (r = 0.016) respectively. Prehospital capnometry had a poor correlation with arterial pCO2 in most emergency patients. Only patients with respiratory disturbances of extrapulmonary origin showed a good correlation between end-tidal CO2 and the arterial pCO2. In severely ill patients the arterio-alveolar CO2-difference was unexpectedly high (> 15 mm Hg). In four patients resuscitation was not successful until compensation of an unexpectedly severe acidosis based upon the findings from blood-gas analysis had been performed. CONCLUSIONS: Arterial blood gas analysis proved to be helpful in the optimal management of out of hospital cardiac arrest. The incidence of severe acidosis in patients undergoing cardiopulmonary resuscitation was 80%. The probability of developing acidosis was found to increase slightly depending on the time elapsed since the beginning of CPR. The application of a calculated buffering of acidosis with sodium bicarbonate showed a good outcome in selected cases. In emergency patients alternative methods fail to detect severe disturbances of the patients oxygen and/or carbon dioxide status and the acid-base balance. Management of prehospital cardiac arrest could be optimized by the routine use of blood gas analysis.

Acidosis↗
PubMed1995

Relationship between quantity of undergraduate science preparation and preclinical performance in medical school.

PURPOSE: The primary purpose of this study was to determine whether a relationship existed between the quantities of undergraduate science education completed by medical students and their subsequent preclinical performances in medical school. The secondary purpose of the study was to determine the nature of any relationship present and to re-verify standard predictors of preclinical performance in medical school. METHOD: This study was undertaken at Albany Medical College in conjunction with Sage Graduate School, Albany, New York. The analysis encompassed 120 systematically and 80 randomly selected medical student academic records (200 total cases) from the entering classes of 1977 through 1992. Twelve distinct variables were collected. Data transformations were completed as required, and the data subsequently standardized. Standard descriptive statistics, correlation between variables, t-tests between systematically and randomly selected groups, and factor analysis were performed on the data collected. RESULTS: It was determined that there was no significant relationship between total hours of undergraduate science completed and average preclinical performance in medical school. In addition, correlation between subdivisions of total hours of undergraduate science (total hours of chemistry, total hours of biology, total hours of math, and total hours of physics) and subdivisions of average preclinical performance (year-one preclinical performance and year-two preclinical performance) also proved to be nonsignificant. However, significant relationships between average preclinical performance and its subdivisions and other standard predictors of preclinical performance (Medical College Admission Test score and science grade-point average) were found to be in line with values in recent literature. In addition, significant relationships were found with the National Board of Medical Examiners Part I examination. Factor analysis of all variables yielded three underlying factors: medical school preclinical performance factor, undergraduate performance factor, and quantity of non-life-sciences factor. CONCLUSION: Quantity of science-based undergraduate premedical education, either in its entirety or in subdivisions, did not materially affect the performances of the selected medical school students in their preclinical years of medical school.

Achievement↗
PubMed2001

Preclinical syndromes predict dementia: the Sydney older persons study.

OBJECTIVES: To identify if preclinical syndromes for Alzheimer's disease, vascular dementia, and Parkinson's disease and related dementias exist. Identification of dementia at early or even preclinical stages has important implications for treatment. METHODS: A community dwelling sample of 647 subjects aged 75 and over at recruitment were followed up for a mean period of 3.19 years (range 2.61 to 4.51 years). Each subject was asked to participate in a medical assessment which included a standardised medical history examining both past and current health and medication usage; a neuropsychological battery (mini mental state examination, Reid memory test, verbal fluency, subsets of the Boston naming test and similarities, clock drawing and copied drawings) and physical examination. Preclinical syndromes for the three predominant dementias (Alzheimer's disease, vascular dementia and Parkinson's disease, and related dementias) and their combinations were defined using cognitive, motor, and vascular features. Their longitudinal outcome as defined by death and dementia incidence was examined. RESULTS: Preclinical syndromes affected 55.7% (n=299) of subjects. Preclinical syndromes showed a trend for an increased odds of death (odds ratio 1.72, p=0.056) and a significantly increased odds of developing dementia (odds ratio 4.81, p<0.001). Preclinical syndromes were highly sensitive, detecting 52 of 58 (89.7%) incident dementias. Two hundred and sixteen of 268 (80.6%) preclinical subjects did not show dementia over the 3 year period (positive predictive value 19.4%). Subjects defined as having a combination of cognitive, extrapyramidal, and vascular features were at greatest risk of progressing to dementia. CONCLUSIONS: Preclinical syndromes were sensitive and significant predictors of dementia. In view of their poor positive predictive value, the preclinical syndromes as defined in this study remain a research tool needing both definitional refinement and greater periods of observation. Multiple coexistent preclinical disorders resulted in a greater incidence of dementia, providing evidence for an additive role between multiple disorders.

Aged↗
PubMed1998

Examination of the preclinical visit in a bachelor of nursing program.

When nursing entered the tertiary sector in 1985 the preclinical visit was introduced and became accepted practice. The initial purpose of the preclinical visit was to inform and prepare Clinical Facilitators and Nursing Unit Managers for undergraduate nursing students' clinical experience. The preclinical visit was perceived as a significant factor which potentially impacts on the quality of student learning within the clinical environment. Initial planning of the preclinical visit shapes and determines the outcomes of the clinical experience for all participants. Students personal and professional development often depend upon how well they are received in the ward area. Despite the emphasis placed on the significance of the preclinical visit, its effectiveness has not been evaluated. Ten years after the introduction of nursing to tertiary education, the preclinical visit was evaluated by a group of academics and clinicians who perceived that the preclinical visit was not achieving the desired outcomes. A survey using a convenience sample of Nursing Unit Managers and Clinical Facilitators was conducted at a major metropolitan teaching hospital in New South Wales. This paper reviews the findings of the study evaluating the preclinical visit. From the results of the study it is evident that a structured, clear format is required for the preclinical visit to be effective.

Attitude of Health Personnel↗
PubMed2006

Detection of preclinical scrapie from serum by infrared spectroscopy and chemometrics.

In this study we describe a methodology for diagnosing preclinical scrapie infection in hamsters from serum by a combination of Fourier-transform infrared (FT-IR) spectroscopy and chemometrics. Syrian hamsters (Mesocricetus auratus) were orally inoculated with the 263K scrapie agent, or mock-infected, and sera were obtained at 70, 100 and 130 days post infection (dpi) and at the terminal stage of scrapie (160 +/- 10 dpi). The analysis of hamster sera by FT-IR spectroscopy and artificial neural networks (ANN) confirmed results from earlier studies which had indicated the existence of disease-related structural and compositional alterations in the sera of infected donors in the terminal stage of scrapie [Schmitt et al. (2002) Anal Chem 74:3865-3868]. Experimental data from sera of animals in the preclinical stages of scrapie revealed subtle but reproducible spectral variations that permitted the identification of a preclinical scrapie infection at 100 dpi and later, but not at 70 dpi. The IR spectral features that were discriminatory for the preclinical stages differed from those of the terminally ill individuals. In order to reliably identify scrapie-negative as well as preclinical (100 and 130 dpi) and terminal scrapie-positive animals, a hierarchical classification system of independent artificial neural networks (ANN) was established. A "toplevel" ANN was designed which discriminates between animals in the terminal stage of scrapie and preclinical scrapie-positive or control animals. Spectra identified by the "toplevel" ANN as preclinical or controls were then further analyzed by a second classifier, the "sublevel" ANN. Using independent external validation procedures, the toplevel classifier produced an overall classification accuracy of 98%, while the sublevel classifier yielded an accuracy of 93%, indicating that scrapie-specific serum markers were also present for preclinical disease stages. Possible spectral markers responsible for the discrimination capacity of the two different ANNs are discussed.

Animals↗
PubMed2000

Distinction between preclinical Alzheimer's disease and depression.

OBJECTIVE: To assess the prevalence of depression in subjects with preclinical Alzheimer's disease (AD) and to investigate the possibility of differentiating subjects with preclinical AD and depression from subjects with depression-related cognitive impairment. DESIGN: A prospective, observational cohort study. SETTING: An outpatient memory clinic of a university-affiliated hospital. PARTICIPANTS: Nondemented subjects with cognitive impairment older than 55 years (n = 111) without neurological or somatic causes for the cognitive impairment. MEASUREMENTS: At baseline, data were collected on patient characteristics, the severity of depression, and cognitive functioning. The course of the cognitive impairment and the presence of dementia were assessed after 2 and 5 years. RESULTS: Twenty-five subjects had preclinical dementia with Alzheimer's type dementia at follow-up. Sixty percent of these subjects (n = 15) were depressed at baseline. Subjects with depression and preclinical AD had at baseline a poorer performance on the cognitive tasks and were older than the subjects with depression-related cognitive impairment. Logistic regression with backward step selection selected age and memory performance as the best predictors for Alzheimer's type dementia in the depressed subjects. The specificity of these predictors for the diagnosis of future Alzheimer's type dementia in depressed subjects was 94%, sensitivity was 90%, positive predictive value was 90%, and negative predictive value was 94%. CONCLUSIONS: Depression is common in preclinical AD. Depressed subjects with preclinical AD can be accurately differentiated from subjects with depression-related cognitive impairment by age and the severity of the memory impairment. Research that aims to investigate preclinical AD should not exclude a priori subjects with depression inasmuch as preclinical AD is often accompanied by depression.

Aged↗
PubMed2007

Specific psychiatric manifestations among preclinical Huntington disease mutation carriers.

BACKGROUND: Despite the need for significant clinical intervention owing to the psychiatric manifestations of Huntington disease (HD), there has been a paucity of studies specifically designed to evaluate these symptoms prior to disease diagnosis. OBJECTIVES: To investigate whether the Symptom Checklist 90-Revised (SCL-90-R) and the Center for Epidemiological Studies Depression Scale can be used to detect psychiatric manifestations among preclinical mutation carriers with absent or minimal motor signs of HD. DESIGN, SETTING, AND PARTICIPANTS: Individuals at risk for or recently diagnosed with HD were recruited and then evaluated at Indiana University School of Medicine, Indianapolis. All of the subjects completed a uniform clinical evaluation that included the Unified Huntington's Disease Rating Scale-99, molecular testing to determine HD mutation status, the SCL-90-R, and the Center for Epidemiological Studies Depression Scale. The sample was divided into 4 study groups: 171 individuals in the nonmutation carrier group; 29 with minimal, if any, motor signs of HD in the preclinical mutation carrier group 1; 20 with motor abnormalities suggestive of HD in the preclinical mutation carrier group 2; and 34 in the manifest HD group. MAIN OUTCOME MEASURES: Scores on the SCL-90-R and Center for Epidemiological Studies Depression Scale were compared. RESULTS: Five SCL-90-R symptom dimensions (obsessive-compulsive, interpersonal sensitivity, anxiety, paranoid ideation, and psychoticism) demonstrated a significant group effect (P < or = .04). The preclinical mutation carrier group 2 and the manifest HD group scored significantly higher on all 5 dimensions as compared with the nonmutation carrier group. The preclinical mutation carrier group 2 scored significantly higher than the nonmutation carrier group for 3 of the SCL-90-R symptom dimensions (anxiety, paranoid ideation, and psychoticism). A significant group effect was found on the Center for Epidemiological Studies Depression Scale (P = .04). The frequency of depressive symptoms was significantly higher in the manifest HD group and the preclinical mutation carrier group 2 as compared with the nonmutation carrier group. CONCLUSION: This study identified specific psychiatric symptom dimensions that differentiate nonmutation carriers from individuals in the early preclinical stages of HD who are either symptom free or have minor nonspecific motor abnormalities.

Adult↗
PubMed1999

Importance of preclinical studies in the development of drugs for treatment of osteoporosis: a review related to the 1998 WHO guidelines.

Osteoporosis, which is defined as a disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk, is a major health issue worldwide. Among the various strategies to prevent and cure this devastating ailment, an important objective is the development of new efficacious and safe drugs. This situation prompted the World Health Organization (WHO) to provide a comprehensive statement of guiding principles for the design, implementation and interpretation of both preclinical testing and clinical trials in osteoporosis. These guidelines, which are now available, underline the crucial importance of the preclinical evaluation, particularly for assessing the effect of an intervention on bone strength. This concept is heightened by the lack of a validated technique for noninvasively evaluating bone strength in humans and the multiple difficulties and heavy burden inherent in the evaluation of fracture rate in clinical trials. The WHO guidelines emphasize that a comprehensive and adequate preclinical program is expected to provide key information on the relationship between bone mass and strength and thus attenuate the burden of clinical studies. The present report provides a review of experimental evidence in support of the preclinical program as proposed in the WHO guidelines. This program is based on the recent development and refinement of animal models of osteoporosis that mimic the human condition according to the conceptual definition of the disease. Many preclinical studies carried out in appropriate animal models with agents that exert either antiresorbing or anabolic effects on bone indicate that they have been highly predictive of the drug action in humans in terms of both bone mass and remodeling, as well as of bone strength whenever fracture rate has been documented in clinical trials. Based on this evidence the WHO guidelines propose strategies according to which the results of preclinical evaluation will determine the end-points required in the different phases of the clinical development of the drug. Such a distribution of task assignment between preclinical and clinical programs should optimize the progress of research available to patients already suffering from or at risk of osteoporosis.

Animals↗
PubMed2001

Self-reported preclinical disability identifies older women with early declines in performance and early disease.

There appears to be a preclinical stage of physical disability which precedes onset of task difficulty (disability) in those who develop disability progressively as a result of chronic disease. Such a stage provides a basis for identifying older adults at risk of becoming disabled. This cross-sectional study evaluated whether a preclinical stage of physical function identified by self-report is associated with decrements in objective physical performance measures or increases in disease; that is, whether these measures, in those with preclinical disability, are intermediate between individuals who report no difficulty and no preclinical changes and those who report difficulty. The Women's Health and Aging Study II, an observational study of 436 women 70-80 years of age who were among the two-thirds least disabled living in the community. Participants were sampled from the HCFA Medicare eligibility lists and were determined eligible if they reported no difficulty, or difficulty in only one of four domains of physical function: mobility, upper extremity, IADL and ADL tasks. At the first follow-up (18 months after baseline), participants completed questionnaires on physical functioning for tasks in each of these domains, with possible answer options for each task: they had (1) difficulty (disabled); (2) no difficulty and no modification of task performance (High Function); or (3) no difficulty but reported modification and/or change in frequency of task performance (a self-report measure of preclinical disability predictive of incident difficulty). At the same visit, standardized, objective measures of function and disease were obtained, including measured walk; chair stands; strength: hip flexion, knee extension, ankle dorsiflexion, and grip; balance: function reach, single leg stand, tandem stand; joint exam: hip pain on passive motion and knee pain or tenderness; spirometry; ankle:arm blood pressure ratio; visual function: acuity, contrast sensitivity, stereopsis; and graded treadmill exercise test. Data were analyzed from the first follow-up examination. Physical performance decreased, and disease frequency increased, in association with decreasing self-reported mobility function (in walking one-half mile and climbing 10 steps), across three self-report categories: High Function, Preclinical Disability (Task Modification but No Difficulty) and Disability (Difficulty). These findings pertained for measures of walking speed, balance, strength, and knee and hip osteoarthritis. Self-reported level of function predicted differences in ranges as well as means for walking speed, balance and strength. These findings indicate a physiologic basis for self-reported function, including preclinical disability, specifically that different levels of disease severity, impairments and physical performance are concurrently associated with different categories of self-reported function. They also suggest new avenues for screening and intervention to prevent disability.

Aged↗
PubMed2001

Diagnosis of preclinical Alzheimer's disease in a clinical setting.

INTRODUCTION: The aim of the study was to investigate whether the preclinical stage of Alzheimer's disease (AD) can be diagnosed in a clinical setting. To this end we investigated whether subjects with preclinical AD could be differentiated from subjects with nonprogressive mild cognitive impairment and from subjects with very mild AD-type dementia. METHODS: Twenty-three subjects with preclinical AD, 44 subjects with nonprogressive mild cognitive impairment, and 25 subjects with very mild AD-type dementia were selected from a memory clinic population. Variables that were used to differentiate the groups were demographic variables, the Mini-Mental State Examination score, performance on cognitive tests, measures of functional impairment, and measures of noncognitive symptomatology. RESULTS: Age and the scores for the delayed recall task could best discriminate between subjects with preclinical AD and subjects with nonprogressive mild cognitive impairment. The overall accuracy was 87%. The score on the Global Deterioration Scale and a measure of intelligence could best discriminate between subjects with preclinical AD and subjects with very mild AD-type dementia. The overall accuracy was 85%. CONCLUSIONS: Subjects with preclinical AD can be distinguished from subjects with nonprogressive mild cognitive impairment and from subjects with very mild AD-type dementia. This means that preclinical AD is a diagnostic entity for which clinical criteria should be developed.

Aged↗
PubMed1996

The effects of preclinical dementia on estimates of normal cognitive functioning in aging.

Individuals with preclinical dementia have begun to decline cognitively, but still perform within normal limits on cognitive testing. As a group, subjects with preclinical dementia have lower scores on neuropsychological tests than their dementia-free counterparts. This study examines the effects of preclinical dementia on estimates of normal cognitive function in the aged using data from a longitudinal study. Individuals with preclinical dementia at baseline were retrospectively identified based on subsequent development of dementia. Age-adjusted norms were computed using baseline data for the Selective Reminding Test and the WAIS verbal and performance scores, both including (conventional norms) and then excluding (robust norms) preclinical cases. The results indicate that by failing to exclude preclinical dementia, conventional normative studies underestimate the mean, overestimate the variance, and overestimate the effect of age on cognitive measures. Methods are discussed for selecting robust elderly samples that are relatively free of contamination by preclinical dementia.

Age Factors↗