Pragmatism and probabilities in dementia.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to E B Larson.
Explore the source record for details and available documents.
OBJECTIVE: To study the clinical course of Alzheimer-type dementia and those factors that might predict or influence the length of survival. DESIGN: A prospective cohort study. PARTICIPANTS: One hundred and twenty-six patients diagnosed with Alzheimer-type dementia were selected from among 200 consecutive outpatients evaluated for suspected dementia from 1980 to 1982. All 126 patients had at least 6 years of follow-up. SETTING: All patients were initially seen as outpatients at a university hospital. MEASUREMENTS AND MAIN RESULTS: Survival analysis was done using Kaplan-Meier estimates and the Cox proportional hazards model. The mean age at symptom onset was 73.9 years and at enrollment in the study, 77.6 years. The median survival from time of enrollment in the study was 5.3 years (range, 0.2 to 7.2+ years) and from symptom onset, 9.3 years (range, 1.8 to 16+ years). Dementia severity, as measured by the Mini-Mental State Examination (MMSE), was strongly associated with survival (P less than 0.001); the median survival of patients with scores of 18 or below was 3 years less than that of patients with scores above 18 (relative risk, 2.7; 95% CI, 1.6 to 4.4). Comorbid conditions and symptom duration were not related to survival. A multivariate analysis of age at symptom onset and of historical features showed that the combination of wandering and falling (relative risk, 2.1; 95% CI, 0.9 to 5.2) and the presence of behavioral problems (relative risk, 1.4; 95% CI, 0.7 to 2.9) at the time of evaluation appeared to adversely affect survival. CONCLUSIONS: Length of survival in patients with Alzheimer-type dementia is highly variable; severity of disease (not duration), the combination of wandering and falling, and behavioral problems are associated with shorter survival. Our findings, if confirmed, may provide prognostic information for families and professionals and suggest areas in which interventions to improve survival might be focused.
In a multicenter, randomized clinical trial, we assessed the early neurologic development of 93 children born prematurely whose heart rates were monitored electronically during delivery and compared it with that of 96 children born prematurely whose heart rates were periodically monitored by auscultation. All the children were singletons with cephalic presentation, and all weighed less than or equal to 1750 g at birth. The mental and psychomotor indexes of the Bayley Scales of Infant Development (standardized mean score +/- SD, 100 +/- 16) and a formal neurologic examination were administered at three follow-up visits (at 4, 8, and 18 months of age, corrected for gestational age). At 18 months, the mean mental-development scores in the groups receiving electronic fetal monitoring and periodic auscultation were 100.5 +/- 2.4 and 104.9 +/- 1.8, respectively (P greater than 0.1). The mean psychomotor-development scores in the two groups at 18 months were 94.0 +/- 2.4 and 98.3 +/- 1.8, respectively (P greater than 0.1). The incidence of cerebral palsy was higher in the electronically monitored group--20 percent as compared with 8 percent in the group that was monitored by auscultation (P less than 0.03). In the electronic-fetal-monitoring group (but not in the periodic-auscultation group), the risk of cerebral palsy increased with the duration of abnormal fetal-heart-rate patterns, as assessed by retrospective review (chi 2 trend = 12.71, P less than 0.001). The median time to delivery after the diagnosis of abnormal fetal-heart-rate patterns was 104 minutes with electronic fetal monitoring, as compared with 60 minutes with periodic auscultation. We conclude that as compared with a structured program of periodic auscultation, electronic fetal monitoring does not result in improved neurologic development in children born prematurely.
A case-control study of Alzheimer's disease (AD) was conducted to evaluate the roles of family history of dementing disease and AD, and medical conditions, particularly those related to the viral and immune hypotheses in AD. One hundred and eighty-three clinically diagnosed patients were identified between 1980 and 1985 through the Geriatric and Family Services clinic at the University of Washington hospital, and 18 patients were identified during the same time period through the Veteran's Administration Medical Center in Seattle, Washington. Telephone interviews were conducted with spouses (87.7%) and children (12.3%) of the patients. Each patient was matched to a friend or nonblood relative of the patient by age, sex, and the relationship between the patient and his or her respondent, for a total of 130 matched pairs. The odds ratio for AD was elevated if a first-degree relative was reported to have a history of dementia (odds ratio, 2.21; 95% confidence interval, 1.17 to 4.18). This risk was especially elevated if a sibling was affected (odds ratio, 4.04; 95% confidence interval, 1.37 to 11.90); the highest risk to the proband was observed if a sibling had presumed AD (odds ratio, 5.92; 95% confidence interval, 1.59 to 21.96). The risk increased with increasing numbers of first-degree family members affected for both a history of dementia and presumed AD. We found little difference between patients and control subjects with respect to the age of the mother or father at the time of the subject's birth. No statistically significant differences were observed between the two groups with regard to conditions that might support the immune and viral hypothesis in AD, smoking, or alcohol problems.
Explore the source record for details and available documents.
The association between exposure to aluminum through the lifetime use of antiperspirants and antacids and Alzheimer's disease (AD) was explored in a case-control study of 130 matched pairs. Cases were clinically diagnosed between January 1980 and June 1985 at two geriatric psychiatric clinics in Seattle, Wash. Controls were friends or non-blood relatives of the case. Subjects were matched by age, sex, and the relationship between the case and his or her surrogate. For all antiperspirant/deodorant use, regardless of aluminum content, there was no association with AD (adjusted odds ratio (OR) = 1.2, 95% CI = 0.6-2.4). For aluminum-containing antiperspirants, the overall adjusted OR was 1.6 (95% CI = 1.04-2.4) with a trend toward a higher risk with increasing frequency of use (p for trend = 0.03), the adjusted OR in the highest tertile being 3.2. For antacids regardless of aluminum content, the overall adjusted OR was 3.1 (95% CI = 1.2-7.9). Here, a steep dose-response gradient was found (p for trend = 0.009), with an adjusted OR for the highest tertile of 11.7. However, when only aluminum-containing antacids were analyzed, the overall adjusted OR was only 0.7 (95% CI = 0.3-2.0) and there was no significant dose-response trend. These results are provocative but inconclusive due to methodologic problems relating to the necessary use of surrogate respondents and the long time period of potential exposure for this dementing disease.
The concept of the reliability of a measure can also be applied to its change over time. In this study we consider the growth curve approach to estimating the reliability of change, in the context of cognitive status as measured by the Mini-Mental State Examination (MMSE) and the Blessed and Tomlinson Dementia Rating Scale (DRS) in patients with senile dementia of the Alzheimer type (SDAT). The reliability of the estimates of change is shown to depend primarily upon the length of time of observation, not the number of observations made. The estimated reliability coefficient for the change in MMSE (or DRS) at 6 months is 0.16 (or 0.08); at 2 years is 0.75 (or 0.57). The concept of signal-to-noise ratio is introduced to compare reliabilities in change scores.
The cost of therapies like bone marrow transplantation has been an important consideration for several decades. Bone marrow transplantation is becoming increasingly accepted as an effective treatment for hematologic disorders, including acute nonlymphocytic leukemia. To find suitable donors, bone marrow donor registries are being developed. The first-year costs of establishing an unrelated bone marrow donor registry are reported here. First-year costs are largely due to personnel costs and HLA typing charges. The cost per registrant decreases over time, but further decreases due to economies of scale are limited by the continued fixed requirement for HLA typing. Data are presented by separating costs into six unique categories, thereby allowing other blood centers to estimate start-up costs based on our experience.
Alzheimer's disease is characterized by progressive cognitive decline. However, little is known about the "typical" rate of decline, the degree of individual heterogeneity evident in decline, or the types of factors that influence such decline. This study investigated these questions in a sample of 106 patients with Alzheimer's disease, assessed at 1-5 points in time, spanning up to three years. At each time point, the Mini-Mental State Exam, a measure of global cognitive function, was administered to all patients. Measures of behavioral disturbance (including the presence/absence of hallucinations, depression, incontinence, wandering, and agitation), health status (including presence/absence of neurological, cardiovascular, and other diseases), and descriptive information (such as gender, age at time of onset, and duration of deficits) were obtained at entry into the study. A two-stage random effects regression model was fit to the data and then used to assess the effect of these behavioral, health, and descriptive measures on the rate of decline. Results indicate that the rate of cognitive decline in Alzheimer's disease is quite variable. Patients with various health and behavioral problems declined at a rate between 1.4 and 5 times faster than patients without such problems. Alcohol abuse, additional neurological disease, and agitation were significantly related to rate of decline. Overall number of problems was not. The association of these problems with accelerated decline may have prognostic and treatment implications.
Explore the source record for details and available documents.
The relation between head trauma and Alzheimer's disease was one of four major risk factors explored in a case-control study of 130 matched pairs; cases were clinically diagnosed between January 1980 and June 1985 at two geriatric psychiatric clinics in Seattle, Washington, and controls were friends or nonblood relatives of the cases. Subjects were matched by age, sex, and relationship between the case and his or her surrogate respondent. Head injuries which resulted in a loss of consciousness or which caused the subject to seek medical care were documented by means of interviews with surrogate respondents. A history of head injury was recorded for 24% of the cases and 8.5% of the controls, yielding an odds ratio of 3.5 (95% confidence interval 1.5-8.3) in conditional logistic regression analysis adjusted for age at onset of disease symptoms and family history of Alzheimer's disease. The estimated risk of Alzheimer's disease increased as the time between the last head trauma event and the onset of disease symptoms diminished (p = 0.002). This trend remained statistically significant (p = 0.006) when head injuries which occurred within 5 years of onset of the disease were excluded from the analysis. There was some difference between cases and controls for the average duration of unconsciousness in events accompanied by such a loss, but this was not statistically significant. The two groups were also similar in the circumstances surrounding the injuries and in the frequency of alcohol problems. This is the third case-control study to find a statistically significant association between head trauma and Alzheimer's disease.
To determine interrater reliability of dementia diagnosis, 4 physicians experienced in the evaluation of dementia patients applied 3 sets of diagnostic criteria to each of 62 patients, based on a standardized set of medical record information. All patients had undergone similar examinations and follow-up to establish the initial clinical diagnosis (76% had autopsy). Raters were blind to the diagnosis and to follow-up information after the initial evaluation period. This paper presents interrater agreement (kappa values) for a diagnosis of Alzheimer's disease using the American Psychiatric Association diagnostic criteria from the Diagnostic and Statistical Manual (DSM-III), the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) criteria for the clinical diagnosis of Alzheimer's disease, and the Eisdorfer and Cohen Research Diagnostic Criteria (ECRDC) for primary neuronal degeneration. The NINCDS showed somewhat higher average interrater reliability (kappa = 0.64) than the DSM-III (kappa = 0.55) and considerably higher interrater reliability than the ECRDC (kappa = 0.37). One rater displayed conspicuously lower levels of interrater reliability than the other 3, especially in DSM-III and ECRDC. This study indicates that interrater reliability of DSM-III and NINCDS criteria are comparable. Documentation of interrater reliability and, if necessary, training to improve reliability is an important consideration in research where different observers are diagnosing dementing illnesses.
To examine the validity of criteria-based (clinical) diagnosis of Alzheimer's disease (AD), 4 physicians experienced in the evaluation of dementia patients applied 3 sets of diagnostic criteria to each of 62 patients based on standardized medical record information. Diagnostic outcome was validated by neuropathologic examination (completed previously) for all (43) demented patients and 4 nondemented patients and by follow-up in the remainder (15) with no dementia. Raters were blind to the composition of the study group as well as to the clinical and pathologic diagnoses. We evaluated 3 diagnostic criteria sets for AD: the American Psychiatric Association diagnostic criteria from the Diagnostic and Statistical Manual (DSM-III), the NINCDS-ADRDA Work Group criteria for the diagnosis of Alzheimer's disease (NINCDS), and the Eisdorfer and Cohen research diagnostic criteria for primary neuronal degeneration (ECRDC). ECRDC had the highest specificity (0.88) but also the greatest odds of false-negative diagnosis (LRneg = 0.61, sensitivity = 0.46). NINCDS had the best sensitivity (0.92, specificity = 0.65), and DSM-III showed intermediate values (sensitivity = 0.76, specificity = 0.80). We conclude that the investigator or clinician who wishes to ensure that patients classified as AD are more likely to be AD should choose DSM-III, whereas the investigator who wishes to include the greatest number of AD cases, seldom assigning a diagnosis of no AD to a true case, should choose NINCDS.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
This discussion was selected from the weekly Grand Rounds in the Department of Medicine, University of Washington School of Medicine, Seattle. Taken from a transcription, it has been edited by Paul G. Ramsey, MD, Associate Professor of Medicine, and Philip J. Fialkow, MD, Professor and Chair of the Department of Medicine.
Explore the source record for details and available documents.
To compare the cost effectiveness of bone marrow transplantation and conventional chemotherapy, we evaluated the resources used in the care of adult patients with acute nonlymphocytic leukemia who were enrolled in a prospective trial and received induction chemotherapy at a single university hospital. Nineteen patients were subsequently treated with chemotherapy and 17 with transplantation. Cost accounting began with induction chemotherapy and extended over a five-year period. Costs were estimated by means of a resource-based, multivariate prediction model. The transplantation and chemotherapy groups had virtually equivalent use of resources (hospital days, laboratory tests, blood products, and radiologic and operative procedures) over five years, except for a 10-fold increase in the use of the intensive care unit for the patients who underwent transplantation (P less than 0.001). The total costs over five years were estimated at $193,000 per patient for transplantation and $136,000 per patient for chemotherapy (P = 0.02). At five years, the costs per year of life saved ("life-year") were nearly equal ($62,500 per life-year for transplantation vs. $64,000 per life-year for chemotherapy) because of the better rate of disease-free survival in patients who underwent bone marrow transplantation. We conclude that the cost effectiveness of bone marrow transplantation to treat acute nonlymphocytic leukemia compares favorably with that of chemotherapy and could be further enhanced if intensive care resources were used more selectively.