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E B Larson

Publications and source records attributed to E B Larson.

At least 91 records · Page 5Linked to original sources
PubMed1996

Head circumference as a measure of cognitive reserve. Association with severity of impairment in Alzheimer's disease.

BACKGROUND: Recent studies suggest that larger brain size may offer some protection against the clinical manifestations of Alzheimer's disease. However, this association has not been investigated in population-based studies. METHOD: The relationship between head circumference, a measure of premorbid brain size, and score on the Cognitive Abilities Screening Instrument (CASI) was studied in a population of 1985 Japanese-Americans aged 65+ living in King County, Washington, USA. RESULTS: After adjusting for age, sex and education, head circumference was positively associated with CASI score (b = 3.8, 95% Cl: 2.2, 5.4; P = 0.0000), but not with diagnosis of probable AD (odds ratio = 0.87, 95% Cl: 0.33, 1.87). When the data were stratified by AD status, no association was seen among controls (b = 1.6, 95% Cl: -1.7, 5.1; P = 0.4), whereas a strong effect was present among cases (b = 35.3, 95% Cl: 12.2, 68.4: P = 0.006). CONCLUSIONS: These results suggest that persons with AD with smaller head circumference either had the disease longer or progressed more rapidly than those with larger head circumference. Improvement in environmental factors in prenatal and early life that partially determine completed brain/head size may have consequences for the late-life expression of Alzheimer's disease in vulnerable individuals.

Aged↗
PubMed1996

Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?

Despite recent advances in the molecular genetics of Alzheimer's disease (AD), several fundamental questions concerning risk of illness are unresolved, namely, if Mendelian factors account for the incidence of the disease, and if AD is an inevitable consequence of the aging process. This study was designed to address these issues and other aspects of familial aggregation of the disorder. A consecutive sample of 1,694 patients who met criteria for a diagnosis of probable or definite AD were ascertained in 13 centers participating in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) project. Lifetime risk and age at onset of AD among various strata of 12,971 first-degree relatives was estimated using survival analysis procedures. The lifetime risk of AD in first-degree relatives was 39.0% +/- 2.1% by age 96 years. Age-specific risk of AD declined after age 90 and the data set included 61 apparently unaffected persons who survived to age 96 without becoming demented. Female relatives had a higher risk of AD than male relatives at all ages. By age 80, children of conjugal AD couples had a cumulative risk of 54%, 1.5 times greater than the sum of the risks to children having affected mothers or fathers, and nearly 5 times greater than the risk to children having normal parents. Children of affected fathers had a cumulative risk that was 1.4 times the corresponding risk to children of affected mothers. Risk assessment in early-onset and late-onset families, using various strategies for determining the age cut-off, yielded contradictory results. These data suggest the following: (1) the lifetime risk among relatives does not support a simple autosomal dominant inheritance pattern of disease; (2) women are innately more susceptible to AD than men; (3) the proportion of hereditary cases may be higher in men than women; (4) distinction between early- onset and late-onset forms of AD has little meaning in the absence of a biological marker; (5) the risk of AD decreases after age 90; and (6) AD therefore may not be an inevitable concomitant of the aging process, a conclusion that has profound implications for basic and applied AD research. The age- and sex-specific lifetime risks derived from this study are sufficiently robust to be a reliable source of information for counseling relatives of AD patients.

Age Factors↗
PubMed1996

Predictors of mortality in patients diagnosed with probable Alzheimer's disease.

OBJECTIVE: We sought to identify factors associated with mortality in persons recently diagnosed with probable Alzheimer's disease (AD). BACKGROUND: Predicting mortality in AD in needed both in patient care and public health planning. Previous studies have identified several factors which contribute to mortality in AD, but few longitudinal studies of population-based cohorts exist. METHODS: In a longitudinal follow-up study 327 patients with newly diagnosed probable AD (mean Mini-Mental State Examination [MMSE] score of 20) from a large, stable health maintenance organization were identified. Demographic characteristics, dementia severity, and comorbid conditions were identified at enrollment. Patients were followed longitudinally (median 3.3 years, total 898 person-years). Baseline characteristics were used to predict survival in univariate and multivariate models. RESULTS: Increased mortality was seen in patients with probable AD (9.0 deaths per 100 person-years) compared with the community population adjusted for age and gender (4.3 deaths per 100 person-years). On univariate analysis we found increased age, male gender, impairment on MMSE or Blessed dementia rating scale (DRS), rate of MMSE decline, wandering or agitation, vascular disease, and sensory impairment affecting the ability to read or hear to be moderately associated with decreased survival. After adjusting for age and gender in a multivariate model, Blessed DRS score and sensory impairment affecting the ability to read were independently associated with decreased survival. CONCLUSIONS: Short-term mortality is increased in patients newly diagnosed with probable AD. Measures of dementia severity, measures of general debility, and vascular disease are associated with increased mortality. Of these, general debility and sensory impairment were more strongly associated with shortened survival.

Aged↗
PubMed1996

Influence of apolipoprotein E genotype on the transmission of Alzheimer disease in a community-based sample.

The epsilon 4 allele of the apolipoprotein E locus (APOE) has been found to be an important predictor of Alzheimer disease (AD). However, linkage analysis has not clarified the role of APOE in the transmission of AD. The results of the current study provide evidence that the pattern of transmission of memory disorders differs in nuclear families in which the AD-affected proband did carry an epsilon 4 allele versus those families in which the AD-affected proband did not carry an epsilon allele. Further, risk of AD due to APOE genotype in the probands is modified by family history of memory disorders, suggesting gene-by-gene interactions. Family history remained a significant predictor of AD for affected probands with some, but not all, APOE genotypes in a logistic regression analysis. Though nonadditive in the prediction of AD, APOE genotype and family history acted additively in the prediction of age at AD onset. The results of complex segregation analysis were inconsistent with Mendelian segregation of memory disorders both in families of affected probands who did or did not carry an epsilon 4 allele, yet these two groups had significantly different parameter estimates for their transmission models. These results are consistent with gene-by-gene interactions, but also could result from common elements in the familial environment.

Age of Onset↗
PubMed1995

Solvent exposure as a risk factor for Alzheimer's disease: a case-control study.

This case-control study investigates whether history of organic solvent exposure is associated with increased risk of Alzheimer's disease. The study base includes about 23,000 persons aged 60 years or more from the local membership of a health maintenance organization in Seattle, Washington, who entered the study between 1987 and 1992. Probable Alzheimer's disease cases (n = 193) who had presented with new dementia symptoms were identified, enrolled, and diagnosed by our Alzheimer's Disease Patient Registry following standardized criteria. Control subjects (n = 243), free of dementia and neurologic disease causing dementia, were selected randomly from the study base and frequency matched to cases for age and sex. Proxy informants provided specific solvent exposure history as well as job descriptions likely to involve solvent use as part of a comprehensive risk factor interview. Kappa statistics indicated substantial agreement for control-control proxy solvent responses. History of exposure to one or more solvent groups (benzene and toluene; phenols and alcohols; ketones; other solvents) yielded an adjusted Alzheimer's disease odds ratio of 2.3 (95 percent confidence interval 1.1-4.7); among males only, it increased to 6.0 (95% confidence interval 2.1-17.2). Thus, past exposure to organic solvents may be associated with onset of Alzheimer's disease.

Age Factors↗
PubMed1995

Primary and secondary prevention of alcohol problems: U.S. internist attitudes and practices.

OBJECTIVE: To describe internists' involvement in primary and secondary prevention of alcohol-related problems, and to evaluate relationships between preventive practices and training, attitudes, and work patterns. DESIGN: Cross-sectional survey. PARTICIPANTS: A random sample of 152 board-certified internists, < or = 65 years old, who practiced primary care in the continental United States, was selected from the American Medical Association's master list. Ten were ineligible; 99 (70%) of the remaining 142 internists completed questionnaires. MAIN OUTCOME MEASURES: The authors evaluated the internists' preventive practices, including the frequency with which they assessed patients' alcohol consumption and advised patients about safe levels of alcohol consumption. The authors also evaluated the internists' opinions about safe levels of alcohol consumption, training and attitudes regarding advising patients about safe levels of consumption, and work patterns. RESULTS: Ninety-four percent of the respondents believed they had a responsibility to advise all patients about safe levels of alcohol consumption (primary prevention), though only 30% often/always did so. Eighty percent often/always advised patients who drank three or more drinks daily about safe levels of alcohol consumption (secondary prevention), but many (45%) did not routinely ask patients how much they drank daily. Preventive practices correlated positively with the number of hours/week internists practiced primary care, and with their belief in the effectiveness of preventive advice about alcohol consumption. CONCLUSIONS: Internists believe they have a responsibility for primary prevention of alcohol-related problems, but only a minority actively practice it. In contrast, many internists practice secondary prevention, offering advice about safe alcohol consumption to patients who drink three or more drinks daily. The effectiveness of such secondary prevention is limited, however, by incomplete screening regarding level of alcohol consumption.

Adult↗
PubMed1995

The effect of diagnosing Alzheimer's disease on frequency of physician visits: a case-control study.

OBJECTIVE: Two groups of elderly subjects were studied to see whether patterns of visits to physicians changed after one group received the diagnosis of Alzheimer's disease. DESIGN: Case-control study. SETTING: Health maintenance organization (HMO). PATIENTS/PARTICIPANTS: Two groups of ambulatory subjects (mean age 77 years) were enrolled from an HMO population for this case-control study: 120 cases had probable Alzheimer's disease diagnosed at enrollment, and another 120 cognitively intact controls with similar comorbidity were enrolled after being frequency-matched for age and gender. Exclusion criteria were nursing home admission and death during the study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records were examined for a four-year period: two years prior to and two years following enrollment and diagnosis. Physician visits declined slightly after enrollment for the persons receiving the diagnosis of Alzheimer's disease [17.5/2 years prior vs 16.5/2 years after (NS)], whereas visits increased over time for the controls [13.7/2 vs 16.3/2 (p < 0.05)], hence the rates were similar after enrollment [16.5 vs 16.3 (NS)]. The proportion of subjects with fewer visits during the period after enrollment was higher among the cases than it was among the controls [54% vs 37%; odds ratio = 2.0 (95% confidence interval = 1.6, 3.1)]. Hospitalizations and emergency department use did not change significantly after enrollment. CONCLUSIONS: Physician visit frequency was high before, then decreased after, demented patients received their diagnosis, approaching the frequency in a control population without dementia. This phenomenon cannot be accounted for by nursing home placement, comorbidity, or mortality. Increased hospitalization and emergency department use did not ensue after diagnosis.

Aged↗
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

History of depression as a risk factor for Alzheimer's disease.

Research regarding the possible association between Alzheimer's disease and a history of depression has been inconclusive. Using a case-control design, we assessed the strength of the association between reported history of depression and onset of Alzheimer's disease. We enrolled probable Alzheimer's disease cases (N = 294), who were ascertained and diagnosed by our Alzheimer's Disease Patient Registry, and randomly selected nondemented controls (N = 300) of similar age and gender from the same base population. The mean age (for cases) was 78.5 years. Informants provided data regarding history of depression. "Treated depression" was defined as depression for which a physician/psychologist consultation, medication, or hospitalization had occurred. Restricting treated depression to exclude primary loss or grief reactions, we found a modest association with Alzheimer's disease [odds ratio (OR) = 1.8; 95% confidence interval (CI) = 0.9-3.5] after adjusting for gender, age, education, and type of informant. When these data were stratified by depression onset year, we observed an odds ratio of 2.0 (95% CI = 0.9-4.6) for depression occurring more than 10 years before the onset of dementia symptoms, and an OR of 0.9 (95% CI = 0.2-3.0) for depression onset within 10 years of the onset of dementia symptoms. Thus, depressive episodes occurring well before dementia symptom onset appear to increase the risk of Alzheimer's disease.

Age Distribution↗
PubMed1995

Do surgical brain lesions present as isolated dementia? A population-based study.

OBJECTIVE: To determine the incidence of clinically important subdural hematoma (SDH), hydrocephalus not associated with a recent intracranial bleed, and intracranial tumor that is not obviously metastatic, and to test the sensitivity of a promising decision rule for computerized tomography (CT) in dementia. DESIGN: Population-based, retrospective, sequential case series. SETTING: Staff model health maintenance organization (HMO). PATIENTS: Patients aged 65 years and older with one of the three lesions, diagnosed over a 4.5-year period, identified mainly through computerized databases of hospital discharge diagnoses and a registry of malignant tumors. MEASUREMENTS: Clinical data were based on chart review. The decision rule, based on one that had been previously proposed and tested, stated that CT would be required if any one of 11 clinical criteria were met by a patient with cognitive impairment. Rule sensitivity was evaluated using clinical information recorded before CT. MAIN RESULTS: One hundred forty-five clinically important lesions were identified among 137,100 person-years at risk. Average annual incidence per 100,000 was 46.7 (95% CI 36.0, 59.6) for SDH, 5.8 (95% CI 2.5, 11.5) for hydrocephalus not associated with a recent intracranial bleed, and 53.2 (95% CI 41.7, 66.9) for intracranial tumors that were not obviously metastatic. Using the 65 to 74- year age strata as a reference, the relative risk for SDH was 4.8 (95% CI 2.7, 8.5) in 75 to 84-year-olds and 13.1 (95% CI 7.7, 22.5) in the 85 and older strata. Among 59 patients who presented with cognitive impairment, without altered sensorium or physical evidence of trauma, decision rule sensitivity was 93.2% (95% CI 83.5%, 98.1%). Sensitivity was 90.7% (95% CI 77.9%, 97.4%) in the subgroup that presented to an ambulatory care clinic rather than to an emergency department. CONCLUSIONS: These three lesions, which are the most common surgical lesions that may present as dementia, are rare. Most cases have presentations that easily distinguish them from typical Alzheimer's disease. This case series indicates that it may be feasible to develop a decision rule for the selective use of CT in dementia. Disease spectrum will influence measures of decision rule performance such as sensitivity and specificity.

Aged↗
PubMed1995

Effect of postmenopausal hormonal replacement therapy on mammographic density and parenchymal pattern.

PURPOSE: To measure changes and predictors of change in mammograms obtained in postmenopausal women undergoing continuous combined hormonal replacement therapy (HRT). MATERIALS AND METHODS: Mammograms of 41 postmenopausal women obtained before and 1 year after the initiation of HRT were evaluated blindly according to the quantitative density percentage method and the Wolfe classification system. RESULTS: Mammographic densities increased compared with baseline values in 73% of subjects (mean increase, 6.7%; 95% confidence interval, 2.5%, 11.0%; P = .003). A shift in Wolfe classification from lower to greater parenchymal density was noted in 24% of subjects (P = .016). Multivariate analysis results indicated that the lower the tissue density percentage before treatment, the greater the increase in density percentage after treatment. CONCLUSION: An increase in mammographic density was demonstrated in most subjects undergoing continuous combined HRT and was most pronounced in subjects with a lower baseline density percentage.

Breast↗
PubMed1995

Study of Alzheimer's dementia patients with parkinsonian features.

This paper presents a study to test the hypothesis that a parkinsonian subtype of Alzheimer's disease exists. Twenty-one patients with dementia of the Alzheimer's type (DAT) and coexistent parkinsonian features were matched to 21 DAT control patients without parkinsonian signs. All subjects were drawn from 136 patients with DAT evaluated between 1980 and 1982. Items from a standardized clinical evaluation at the time of diagnosis, from continuous yearly follow-ups, and neuropathologic examination were compared to determine if qualitative differences exist between the two groups. Those with parkinsonian features had significantly shorter duration of symptoms prior to presentation, a trend toward more reports of decreased self-care, and more primitive reflexes on physical examination. While the total Folstein Mini-Mental State Exam (MMSE) scores at presentation were not significantly different, the cases showed greater impairment in language and registration subitems. During follow-up, no differences were observed in performance on MMSE and Dementia Rating Scale scores. Survival curves showed a trend toward poorer survival in the cases. Neuropathologic data were obtained on seven patients with both DAT and parkinsonian features and showed three cases with Alzheimer's disease (AD) alone and four with AD and Parkinson's disease. Four of the DAT control patients were examined neuropathologically, and all had AD without evidence of Parkinson's disease. The results provide preliminary evidence that Alzheimer's patients with parkinsonian signs are a subtype characterized by distinct neurologic signs and a more rapid course.

Aged↗
PubMed1995

The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a screening tool for dementia for a predominantly illiterate Chinese population.

The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) provides ratings of an individual's changes in everyday cognitive functions during the previous 10 years. Original studies conducted in Australia showed that its score was not influenced by the subjects' educational backgrounds and that it performed at least as well as the Mini-Mental State Examination (MMSE) as a screening instrument for dementia. The subjects of the present study were Chinese and included 399 community residents and 61 dementia patients. Their ages ranged from 50 to 92 years; their education levels ranged from 0 to 19 years, and 63% of them had never attended school. We administered the IQCODE to informants and the Cognitive Abilities Screening Instrument (CASI), from which a CASI-estimated score of the MMSE (MMSE-CE) can be obtained, to the subjects. The diagnosis of dementia was made independently by physicians according to the DSM-III-R criteria based on semistructured interview and testing, neurologic examination, and standardized assessments of cerebral vascular disease, Parkinson's disease, and depression. The Chinese IQCODE showed no association with the subjects' education level or gender, low association with their age, and moderately high association with their MMSE-CE score. The area under the receiver operating characteristic curve of the IQCODE was significantly larger than that of the MMSE-CE for the whole group and for the subgroup with 1 to 19 years of education but not for the subgroup with 0 years of education. Nine of the 26 items of the IQCODE could be deleted without appreciable reduction in sensitivity and specificity. The IQCODE (1) can be shortened to 17 items, (2) had good cross-cultural applicability, and (3) was better than the MMSE-CE as a screening tool for dementia in a population with large variation in educational backgrounds.

Age Factors↗
PubMed1995

Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer's disease: a case-control study.

OBJECTIVE: The joint effects of total cholesterol (TC) levels and the APOE genotype in Alzheimer's disease (AD) were evaluated because of previous reports that the APOE locus epsilon 4 allele was associated with both late-onset AD and elevated TC. DESIGN: Logistic regression was used to determine the effects of the APOE genotype, TC, age, and sex on prediction of AD in a community-based study of 206 cases and 276 controls. RESULTS: The relationship of the APOE genotype and AD was dependent on TC, age, and sex. However, current TC level does not fully explain the epsilon 4-Alzheimer's disease association. Affected men with higher TC and age under 80 years had the highest epsilon 4 allele frequencies. The epsilon 4 frequency declined significantly with age. SIGNIFICANCE: A pathologic role of higher TC or cholesterol-based differential survival of epsilon 4-carrying individuals may be involved in the relationship of the epsilon 4 allele with AD. The observed association of the APOE genotype and AD is expected to depend on the age, sex, and TC distributions of a given sample.

Aged↗
PubMed1995

The cost-effectiveness of lung transplantation. A pilot study. University of Washington Medical Center Lung Transplant Study Group.

OBJECTIVE: Lung transplantation is one of the fastest-growing solid organ transplant procedures in the world, yet its cost-effectiveness is unknown. We compared the costs and outcomes of the first 25 patients who received lung transplants at the University of Washington with 24 patients currently on the lung transplant waiting list. DESIGN: Inpatient and outpatient charges were obtained from the hospital billing service and home health agencies. Quality-adjusted life year scores (QALYs) were computed from the following: (1) utility scores obtained through standard gamble interviews, and (2) published survival data from an international lung transplant registry and from studies of patients on lung transplant waiting lists. RESULTS: Transplantation charges averaged $164,989 (median, $152,071). Average monthly charges posttransplant were $11,917 in year 1 and $4,525 thereafter, vs $3,395 for waiting-list patients. Posttransplant utility scores were significantly higher than waiting-list scores (0.80 vs 0.68; p < 0.001). Life expectancy was not greater for lung transplant vs waiting-list patients (5.89 vs 5.32 years; p > 0.05), although quality-adjusted life expectancy did improve significantly. After converting charges to costs, the incremental cost per QALY gained for posttransplant compared with waiting-list patients was $176,817. CONCLUSIONS: Lung transplantation is very expensive, although it can substantially improve quality of life. Two-thirds of care costs are incurred after transplantation. The principal barriers to cost-effectiveness at present are the high cost of postrecovery care and marginal gains in life expectancy compared with conservative care.

Adult↗
PubMed1994

Postmenopausal estrogen replacement therapy and the risk of Alzheimer's disease: a population-based case-control study.

Preliminary animal and human data suggest that estrogens may be protective against Alzheimer's disease in women. In a population-based case-control study at Group Health Cooperative of Puget Sound, Seattle, Washington, the authors compared the exposure of estrogen replacement therapy of 107 female Alzheimer's disease cases with 120 age- and sex-matched controls by using computerized pharmacy data. The cases were obtained from the Alzheimer's Disease Patient Registry of the University of Washington, Seattle, Washington, which is based on the enumerated health plan population from 1987 to 1992. Newly recognized cases of probable Alzheimer's disease according to standardized diagnostic criteria were ascertained, evaluated, and enrolled in the Registry. The controls were selected from the same defined population by stratified random sampling. When the authors applied logistic regression, ever use of estrogens did not show an association with Alzheimer's disease (adjusted odds ratio = 1.1, 95 percent confidence interval 0.6-1.8). Oral and vaginal estrogens yielded similar results. In conclusion, this study provides no evidence that estrogen replacement therapy has an impact on the risk of Alzheimer's disease in women.

Administration, Intravaginal↗
PubMed1994

The clinical efficacy of magnetic resonance imaging in neuroimaging.

PURPOSE: To assess the clinical efficacy of magnetic resonance imaging (MRI) for neuroimaging and to provide guidelines for clinical practice. STUDY SELECTION: After a comprehensive literature search, studies of the diagnostic accuracy of MRI alone or compared with other tests and of any impact on therapeutic choices or patient outcomes were reviewed by independent readers, followed by discussion to reach consensus conclusions. DATA EXTRACTION: Of 3125 citations retrieved, 156 studies with original data could be rated according to methodologic criteria for study design. One article contributed grade A quality information about diagnostic accuracy, 28 were graded B or C, and 113 were graded D. One randomized trial and 2 comparison studies contributed grade B or C information about the impact on therapeutic choices. Only 2 studies surveyed health status before and after magnetic resonance scanning. RESULTS: For most abnormalities, the sensitivity of MRI is equal to or better than competing technologies. Magnetic resonance imaging shows greater contrast and detail than computed tomography (CT) but also shows more clinically silent abnormalities or incidental findings. A few studies found a modest impact on therapeutic choices but no impact on quality of life or disability. Costs for MRI are high. Computed tomography is sufficient for initial diagnosis of most mass lesions or intracranial hemorrhages requiring immediate intervention. Magnetic resonance imaging is more accurate in the temporal lobes, posterior fossa, brainstem, and spinal cord. For lumbar radiculopathy, MRI and plain spinal CT are as accurate as post-myelographic CT and are less invasive. The role of magnetic resonance angiography for carotid artery stenosis is being studied. CONCLUSIONS: Although suggestions for appropriate use of MRI in clinical practice can be made, the supporting evidence in published studies is weak. Firm guidelines for appropriate use of MRI should be based on further clinical research using more rigorous methods.

Angiography↗