Biomedical subjects

S D Edland

Publications and source records attributed to S D Edland.

At least 37 records · Page 2Linked to original sources

PubMed1996

Prevalence of dementia and its subtypes in the Japanese American population of King County, Washington state. The Kame Project.

Studies of Asian populations generally have reported prevalence rates for dementia similar to those of predominantly Caucasian populations, but relative prevalence rates of Alzheimer's disease and vascular dementia have differed. Between May 1, 1992 and May 1, 1994, the prevalence rates of dementia, Alzheimer's disease, and vascular dementia were examined in the Japanese American population aged over 65 years in King County, Washington State. A total of 3,045 eligible individuals were identified in a census of persons who were of at least 50% Japanese heritage. Of 1,985 persons who participated in the baseline examination, 382 individuals of 450 sampled from all cognitive performance strata received a diagnostic evaluation. A total of 107 cases with a Clinical Dementia Rating (CDR) of > or = 1 met criteria for dementia according to the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-III-R); 58 of these cases were diagnosed with Alzheimer's disease and 24 with multi-infarct dementia. The estimated prevalence rate for all dementias was 6.3% (95% confidence interval 5.9-6.8). Prevalence rates for dementia increased continuously with age and were 30%, 50%, and 74% for participants aged 85-89, 90-94, and > or = 95 years, respectively; for Alzheimer's disease, prevalence rates were 14%, 36%, and 58% for these three age groups. Rates for Alzheimer's disease were generally higher among women; for multi-infarct dementia, rates for men and women were similar. In the institutional population, the prevalence rate was 66%, and in the community, 2.9%. Persons with lower education had higher overall rates of dementia than those with higher education, but this tendency became weak and inconsistent when rates were age-stratified. The prevalence of dementia in this geographically defined population of Japanese Americans was somewhat higher than prevalence rates reported from Japan, and the distribution of dementia subtypes more closely resembled that found in Caucasian populations in North America and Europe than previously reported in Asian populations.

Age Distribution↗

PubMed1996

Accelerated loss of telomeric repeats may not explain accelerated replicative decline of Werner syndrome cells.

The Werner syndrome (WS) is characterized by the premature onset and accelerated rate of development of major geriatric disorders, including atherosclerosis, diabetes mellitus, osteoporosis, ocular cataracts, and various neoplasms. Cultures of WS skin-fibroblastlike cells have been previously shown to undergo accelerated rates of decline of the replicative potentials and to exhibit variegated chromosomal translocations and deletions. Since the replicative decline of normal somatic cells is associated with a loss of telomeric repeats, we investigated the kinetics of telomeric repeat loss in WS cells. The mean length of telomere restriction fragments (TRF) from the earliest passages of WS cells studied was not shorter than those of controls, possibly reflecting selective pressure for subsets of cells with relatively high residual replicative capacity. Statistical evidence indicated an accelerated shortening of TRF length in serially passaged WS cultures, but the mean TRF lengths of WS cultures that had ceased replicating were significantly longer than those of senescent controls. Thus, while accelerated loss of telomeric repeats could potentially explain the rapid decline in proliferation of WS cells, it is possible that WS cells exit the cell cycle via mechanisms that differ from those of replicatively senescent cells from control subjects.

Adult↗

PubMed1996

Somatic mutations are frequent and increase with age in human kidney epithelial cells.

We have used a primary cloning assay to determine the frequency of 6-thioguanine (TG)-resistant tubular epithelial cells in kidney tissue from 72 human donors ranging in age from 2 to 94 years. The frequency of TG-resistant mutants ranged from approximately 5 x 10(-5) for donors in the first decade of life to approximately 2.5 x 10(-4) for donors in the eighth and later decades of life. Two different statistical analyses indicated that this increase in mutant frequency is exponential with age. We also observed a 2-fold higher TG-resistant mutant frequency in nephrectomy kidneys containing a coincident renal carcinoma. DNA sequence analyses revealed HPRT gene mutations in each of 14 TG-resistant mutants from seven unrelated donors. Thirteen of these 14 mutants resulted from independent mutational events. These results suggest that somatic mutations are common in renal--and perhaps in other human--epithelia, and thus could play an important role in the genesis of age-associated disease.

Adolescent↗

PubMed1996

Impact of sample selection on APOE epsilon 4 allele frequency: a comparison of two Alzheimer's disease samples.

OBJECTIVE: In a highly selected sample of unrelated Alzheimer's disease (AD) patients, we found that the APOE epsilon 4 allele frequency was higher than previously reported. Differing selection and ascertainment criteria may lead to these differences. To address this possibility, we compared the epsilon 4 allele frequency in two samples of AD patients selected from the same geographical area. SETTING AND PARTICIPANTS: Cases (n = 55) and controls (n = 99) from a research clinic-based sample were compared with subjects (n = 537) from a community-based AD patient sample. The samples consisted of unrelated cases who met NINCDS/ADRDA criteria for probable AD. DESIGN AND MEASUREMENTS: Clinical characteristics and APOE genotype data were obtained from AD cases and controls from both samples. RESULTS: Frequency of APOE epsilon 4 allele in the research cases compared with the community cases (0.45 vs 0.36) was nearly significant. We compared demographic and clinical characteristics that might account for this difference and found that the research cases were younger, had an earlier age of onset, and had more advanced disease than the community cases. After onset age was controlled, there was no overall difference between epsilon 4 allele frequency of the two samples. CONCLUSIONS: We found that the epsilon 4 allele frequency tended to be higher in the research AD sample compared the community-based sample. The two samples differed in several demographic and clinical characteristics. We conclude that research-based samples may lead to enrollment of younger patients with more severe disease who have higher APOE epsilon 4 allele load. This potential selection bias must be considered in the interpretation of studies of APOE allele frequency.

Age of Onset↗

PubMed1996

Attitudes toward use of nursing homes and home care in older Japanese-Americans.

OBJECTIVE: A cohort of 1142 older Japanese Americans was identified to study preferences and attitudes regarding use of long-term care (nursing home or home care). DESIGN: Prospective cohort study. PARTICIPANTS AND SETTING: Older Japanese Americans in King County, Washington. RESULTS: Subjects were asked to consider hypothetical situations in which they were temporarily disabled by hip fracture or permanently disabled by dementing illness. If they fractured a hip, only 12% intended to use a nursing home; 29% intended to recover at home with the help of family or friends; another 54% intended to use paid home health care. If they became demented, the majority (53%) intended to use a nursing home; only 11% intended to rely on family or friends for care, and another 29% intended to use paid home health care. Similar responses were observed when subjects were asked what most members of their family or friends would wish them to do; however, they tended to value the perceived wishes of religious figures or the Japanese American community-at-large less than those of family or friends. Significant correlates with intention to enter nursing homes were lack of social support (unmarried, few or no close relatives or housemates), female gender, and high levels of acculturation into American society (never lived in Japan, English-speaking only). Other factors that were not significantly correlated were health perceptions, satisfaction and life control scales, and health care utilization (hospitalizations and MD visits). In multivariate logistic regression, marital status and level of acculturation were the most powerful independent predictors of intention to enter nursing homes. Age and female gender were predictors of intention to use home care. In the base population of subjects, the prevalence of nursing homes use (5%) was similar to that of the general US older population. CONCLUSIONS: We conclude that older Japanese Americans in the Pacific Northwest often intend to enter nursing homes if they became disabled by dementing illness. Actual use is similar to other older populations. This may be attributable largely to the existence of an ethically appropriate nursing home which is strongly supported by, and familiar to, this close-knit community. Intention to use long-term care services appears to be dependent primarily on the level of social supports and acculturation into American society.

Aged↗

PubMed1996

Increased risk of dementia in mothers of Alzheimer's disease cases: evidence for maternal inheritance.

This study tests the hypothesis of maternal inheritance of AD in families of 118 subjects with this disorder enrolled in The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The parental generation included 24 subjects with dementia. Using the Cox proportional hazards model, we found the age-adjusted mother-to-father relative risk to be 2.8 (95% CI, 1.1 to 7.7). Among a subset of 10 families with one affected parent and at least two affected siblings, the ratio of affected mothers-to-fathers was 9:1. These findings support recent studies that found a high mother-to-father ratio among affected parents of subjects with AD. Together, these results suggest maternal inheritance of AD and are consistent with several hypotheses regarding the genetic nature of AD.

Aged↗

PubMed1996

Bias in slope estimates for the linear errors in variables model by the variance ratio method.

Slope estimates for linear measurement error (errors in variables) models based on assumed knowledge of the ratio of measurement error variances are biased if the underlying linear relationship is anything other than a completely deterministic, law-like relationship. This paper describes an eight-parameter linear measurement error model of general applicability that includes an optional "errors in equations" term (Malinvaud, E., 1980, Statistical Methods of Econometrics) that allows the explicit characterization of the asymptotic bias of such slope estimates when the assumption of a law-like relationship does not hold. This bias may be large, underscoring the importance of recognizing the potential influence of errors in equations in measurement error models.

Analysis of Variance↗

PubMed1995

The effects of normal aging on cortisol and adrenocorticotropin responses to hypertonic saline infusion.

To assess the effects of aging on hypothalamic-pituitary-adrenal (HPA) axis responsivity, we compared the plasma cortisol and adrenocorticotropin (ACTH) responses to hypertonic saline infusion between normal older and young human volunteers. We administered a 90 min hypertonic saline infusion (5% sodium chloride at 0.06 ml/kg/min) and a 90 min placebo infusion (0.9% sodium chloride at 0.06 ml/kg/min) to normal young subjects (n = 13, age = 29 +/- 2 years) and normal older subjects (n = 8, age = 63 +/- 3 years). Plasma cortisol, ACTH, osmolality and arginine vasopressin (AVP) were measured before and at 30 min intervals during the infusions. The rate of increase in plasma osmolality and AVP induced by hypertonic saline infusion was similar between groups. The plasma cortisol increase during hypertonic saline infusion was greater in normal older subjects than in young subjects (p = .03), but a stimulatory effect of hypertonic saline infusion on plasma ACTH was not apparent in either older or young subjects. These results suggest increased sensitivity with human aging to stimulation of cortisol release by hypertonic saline infusion at the adrenocortical level of the HPA axis.

Adrenocorticotropic Hormone↗

PubMed1995

Cognitive decline in Alzheimer's disease: a longitudinal investigation of risk factors for accelerated decline.

BACKGROUND: --Although Alzheimer's disease (AD) is a progressive degenerative condition, there is great intra- and inter-individual variability in rates of cognitive decline. Thus far, little data exist to explain such variability. Studies that have attempted to explain it have often been based on cross-sectional designs, small sample sizes, and clinical population data. They have also failed to correct for level of cognitive function, despite clinical evidence that rate of decline varies among patients with varying levels of cognitive ability. METHODS: This study presents longitudinal data on a community-based sample of 156 patients diagnosed with probable AD, followed annually for one to five years (average age at entry = 79, range 54-91 years). The effect of level of cognitive impairment (as measured by the MMSE and Mattis DRS), demographic characteristics (e.g., education and age), behavioral problems (e.g., agitation), and co-existent health problems (e.g., vascular disease) on rate of decline was investigated via multivariate regression analysis. RESULTS: Study results indicate that the average rate of decline in cognitive function, as measured by the MMSE and mDRS, becomes more rapid as the disease progresses. Higher education, younger age, and agitation at intake were also significantly related to increased rates of cognitive decline.

Aged↗

PubMed1995

Relationship between level of insight and severity of dementia in Alzheimer disease. CERAD Clinical Investigators. Consortium to Establish a Registry for Alzheimer's Disease.

Although the cognitive and psychiatric symptoms associated with Alzheimer disease have received increasing attention over the past decade, the study of insight in this illness has been relatively neglected. This paper reports on the relationship between level of insight and severity of dementia in a large sample of patients with Alzheimer disease, largely with mild to moderately severe dementia. The study is based on data from 670 patients with a research diagnosis of probable Alzheimer disease who were enrolled in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The degree of insight was rated by the examiner on the basis of the patient's answers to questions probing awareness of his or her memory deficits or other symptoms of cognitive impairment. Severity of dementia was assessed using the Clinical Dementia Rating Scale, Short Blessed Test, Blessed Dementia Rating Scale, and Folstein Mini-Mental State Examination. Two-year longitudinal follow-up data on insight level and dementia severity were available for 148 of the 670 patients. Decreased level of insight correlated significantly with severity of dementia as measured by all rating instruments. For the patients followed for 2 years, 33.1% declined in level of insight from the entry level. This decline was statistically associated with more severe dementia as measured by the Blessed Dementia Rating Scale. This study confirms the generally accepted belief that patients with Alzheimer disease experience a progressive loss of insight as the severity of dementia increases. Due to methodologic limitations, we are unable to draw conclusions about loss of insight in patients with very mild cognitive impairment.

Aged↗

PubMed1995

The Behavior Rating Scale for Dementia of the Consortium to Establish a Registry for Alzheimer's Disease. The Behavioral Pathology Committee of the Consortium to Establish a Registry for Alzheimer's Disease.

OBJECTIVE: The purpose of the study was to develop a standardized instrument, the Behavior Rating Scale for Dementia, for rating psychopathology in patients with probable Alzheimer's disease and to conduct a multicenter pilot study of this instrument. METHOD: The rating scale was developed collaboratively on the basis of clinical experience and existing instruments. Items were scaled according to frequency of psychopathology and were administered to an informant who was familiar with the subject. The scale was administered in a standardized manner by trained examiners who had met predetermined certification standards. The study group consisted of 303 subjects with probable Alzheimer's disease who had undergone standardized clinical evaluations by the Consortium to Establish a Registry for Alzheimer's Disease. RESULTS: Subjects had an average of 15 problems rated as present in the preceding month. Wide variability in the nature of disturbances was found, with a number of items rated as present since the illness began but not in the past month. Interrater agreement was high. Factor analysis suggested eight preliminary factors that mapped onto clinically relevant domains: depressive features, psychotic features, defective self-regulation, irritability/agitation, vegetative features, apathy, aggression, and affective lability. CONCLUSIONS: The Behavior Rating Scale for Dementia provides a standardized, reliable measure that can be administered to caregivers of demented subjects. On the basis of the present study, the scale has been revised slightly. After additional studies in progress, the Behavior Rating Scale for Dementia will be available for general use in assessing a wide range of psychopathology in dementia.

Aged↗

PubMed1995

Geographically overlapping Alzheimer's disease registries: comparisons and implications.

In the medical and epidemiologic literature, a registry denotes a data base in which registrants share some common characteristic such as disease category. One criticism of registries is that they frequently collect subjects in a haphazard fashion and, hence, are "nonrepresentative of the population purportedly being represented." In this report, we compare two registries: an incident-based Alzheimer's Disease Patient Registry (ADPR) recruiting subjects for epidemiologic studies from a large health maintenance organization; and an Alzheimer's Disease Research Center (ADRC) registry recruiting subjects for phenomenologic, biologic, and pharmacologic studies. While these registries share personnel, overlap geographically, and use similar diagnostic procedures, they differ substantially in their missions and resulting recruitment strategies. We compared these registries with respect to demographic characteristics and cognitive features at subject entry. Subjects enrolled in the incident-based registry are older and report shorter time between symptom onset and recruitment. They are less demented and mirror the general population demographically more closely than do subjects in the other registry. The ADRC registry contains a much greater proportion of subjects with higher educational attainment.

Age Factors↗

PubMed1995

The CERAD experience, Part VIII: Neuroimaging-neuropathology correlates of temporal lobe changes in Alzheimer's disease.

We compared premortem neuroimaging findings with neuropathologic evidence of temporal lobe atrophy in 20 patients with Alzheimer's disease (AD) confirmed by autopsy. There were significant correlations between temporal horn enlargement observed by neuroimaging and hippocampal atrophy at autopsy, and between the overall cerebral atrophy severity on neuroimaging and scores on the Mini-Mental State Examination. This report confirms previous studies correlating temporal lobe atrophy on neuroimaging with a clinical diagnosis of AD, although more precise neuroimaging techniques are needed for use in multicenter studies of AD.

Alzheimer Disease↗

PubMed1995

Neuropsychological test performance in African-American and white patients with Alzheimer's disease.

Little information exists on the performance of black versus white patients with Alzheimer's disease on neuropsychological tests for dementia. In this study, we compared performance on the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuropsychological battery between white (n = 830) and black (n = 158) patients with Alzheimer's disease enrolled in the CERAD study at 23 university medical centers in the United States. The black patients were older, had fewer years of formal education, and were more impaired in their activities of daily living than were the white patients. After controlling for these characteristics and for duration of the disease and severity of dementia, there were differences in the performance of black and white patients on several of the cognitive measures. Black patients scored lower than whites on tests of visual naming and constructional praxis and on the Mini-Mental State Examination. There were no statistical differences in performance on tests of fluency and word list memory. These findings suggest that cultural or experiential differences may modify performance on specific neuropsychological tests. These factors, in addition to age and educational background, should be considered when interpreting performance on neuropsychological tests in elderly black patients with dementia.

Black or African American↗

PubMed1995

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part XI. Clinical milestones in patients with Alzheimer's disease followed over 3 years.

The rate of cognitive decline, measured by psychometric testing, is widely used to track the progression of Alzheimer's disease (AD). As an alternative approach, we studied clinical measures as markers of the progression of dementia in 343 community-dwelling patients with probable AD enrolled in the multi-center Consortium to Establish a Registry for Alzheimer's Disease (CERAD) project. Subjects received standardized evaluations at entry and at annual follow-up. Decline on the Clinical Dementia Rating, loss of instrumental activities of daily living, failure to recall three words on the Mini-Mental State Examination (MMSE), and decline of the total MMSE score to below 10 were high-risk milestones, with cumulative frequencies exceeding 50% at 3 years. Loss of dressing and toileting activities occurred at intermediate rates, while loss of eating ability was rare. The risk of reaching clinical milestones and the annual rate of cognitive decline on the MMSE were directly correlated. Clinical milestones are useful indices of the progression of dementia in patients with AD.

Activities of Daily Living↗

PubMed1995

Plasma arginine vasopressin response to hypertonic saline infusion in Alzheimer disease.

In this study, we tested the hypothesis that the plasma arginine vasopressin (AVP) response to osmotic stimulation induced by hypertonic saline infusion is blunted in the early and middle stages of Alzheimer disease (AD). Because animal data support stimulatory cholinergic mediation of AVP osmoregulation at a brain level, the AVP response in AD might provide clinically useful information about the status of brain cholinergic systems. Seventeen AD outpatients and eight normal older subjects underwent both a 90-min hypertonic saline infusion and a 90-min control (normal saline) infusion. Substantial increases in plasma osmolality during hypertonic saline infusion were accompanied by substantial and linear increases in plasma AVP in both groups. However, there were no significant differences in AVP responses between AD and normal older subjects. These results do not support the utility of plasma AVP response to hypertonic saline in the assessment of brain cholinergic status in AD.

Aged↗

PubMed1994

Prevalence and incidence of major depression in Alzheimer's disease.

OBJECTIVE: This study examined the prevalence and incidence of major depressive disorder in Alzheimer's disease. METHOD: The authors retrospectively reviewed two large Alzheimer's disease databases, one at the University of Texas Southwestern Medical Center in Dallas and the other at the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The Dallas series contained 264 cases of Alzheimer's disease, of which 153 patients were followed up for an average of 3 years from initial evaluation. The CERAD database contained 1,095 cases and excluded patients with histories of depression at initial evaluation; 325 of these patients were followed up for at least 2 years. Alzheimer's disease was diagnosed according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; major depression was diagnosed according to the DSM-III-R criteria. Most of the patients in these series were dwelling in the community and had had Alzheimer's disease symptoms for approximately 4 years at the time of evaluation. RESULTS: In the Dallas series there was a 1.5% prevalence and a 0% incidence of major depression. In the CERAD series there was a 1.3% 2-year incidence of major depression. CONCLUSIONS: The low prevalence and incidence of DSM-III-R major depression in these patients suggest that for the period of time the patients were followed up, Alzheimer's disease did not predispose to major depression. However, major depression may herald the subsequent onset of dementia. Depression in dementia should perhaps be diagnosed by different criteria.

Aged↗

PubMedDate not supplied

Blomqvist revisited: how and when to test the relationship between level and longitudinal rate of change.

Longitudinal studies are often interested in assessing the relationship between severity (level) and rate of change (slope). Blomqvist describes an estimator of this relationship that has been used in a variety of contexts. This paper reviews and generalizes the Blomqvist method. Most published applications of the Blomqvist method contain substantial bias because they fail to consider and accommodate confounding due to the pooling of multiple age cohorts in a single analysis. We describe this bias, and present an unbiased algorithm consistent with the intentions of Blomqvist. We also explore when it is appropriate to apply the Blomqvist analysis, and what inferences can be made using this statistic. Aetiological inference about premorbid level of function predicting future rate of decline is often desired, but may not be justified when modelling chronic progressive conditions, since differential progression prior to the start of longitudinal follow-up can induce a relationship between level and rate of decline, even in the absence of an aetiologically relevant association. We conclude that aetiological inference by the Blomqvist analysis is not appropriate in most investigations of chronic progressive disease. Using the model to develop descriptive and predictive equations in these circumstances, however, remains appropriate, as does testing simply for clinical heterogeneity in longitudinal rate of decline.

Aged↗