Must dementia remain a silent epidemic?
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Biomedical subjects
E B Larson
Publications and source records attributed to E B Larson.
The utility of apolipoprotein E genotyping in the diagnosis of Alzheimer disease in a community-based case series.
CONTEXT: A recent collaborative study found that apolipoprotein E (APOE) genotype, in conjunction with the clinical diagnosis of Alzheimer disease (AD), was useful in improving diagnostic specificity (correctly not diagnosing AD) relative to the clinical diagnosis alone. Since these samples are particularly enriched with patients with AD and the APOE epsilon4 allele, results may not be generalizable to patients seen in the general medical community. OBJECTIVE: To evaluate the diagnostic utility of the APOE genotype in diagnosing AD in a community-based case series from the largest health maintenance organization in an urban area. DESIGN: We examined the effect of including APOE genotype on the diagnosis of AD in a community-based case series of patients presenting with memory complaints. PATIENTS: Clinical and neuropathologic diagnoses and APOE genotype were obtained from 132 patients who underwent evaluation for dementia and subsequent autopsy. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values given various combinations of clinical diagnoses and the presence of an APOE epsilon4 allele. RESULTS: Of the 132 patients, 94 had neuropathologically confirmed AD, yielding a prevalence of 71%. The clinical diagnosis alone yielded a sensitivity of 84%, an estimated specificity of 50%, and positive and negative predictive values of 81% and 56%, respectively. The presence of an epsilon4 allele alone was associated with an estimated sensitivity of 59%, specificity of 71%, and positive and negative predictive values of 83% and 41%, respectively. Using the presence of clinical AD and an epsilon4 allele decreased the sensitivity to 49% and increased the specificity to 84%. The positive and negative predictive values were 88% and 40%, respectively. Alternatively, the clinical diagnosis of AD or the presence of an epsilon4 allele in individuals not meeting clinical criteria for AD increases the estimated sensitivity to 94% but decreases the specificity to 37%. The positive and negative predictive values were 79% and 70%, respectively. The changes in the sensitivity and specificity for the combined tests relative to clinical diagnosis alone offset each other. For lower prevalence communities, the positive predictive value will be much lower than those observed herein. CONCLUSIONS: Our findings do not support the use of APOE genotyping alone in the diagnosis of AD in the general medical community. Although the presence of an epsilon4 allele in older persons with clinical AD increased the probability of having AD and the absence of an epsilon4 allele in this group decreased the probability of having AD, the association is not strong enough in the differential diagnosis of non-Alzheimer dementia and AD.
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Estimation and sample design in prevalence surveys of dementia.
Population prevalence rates of dementia using stratified sampling have previously been estimated using two methods: standard weighted estimates and a logistic model-based approach. An earlier study described this application of the model-based approach and reported a small computer simulation comparing the performance of this estimator to the standard weighted estimator. In this article we use large-scale computer simulations based on data from the recently completed Kame survey of prevalent dementia in the Japanese-American residents of King County, Washington, to describe the performance of these estimators. We found that the standard weighted estimator was unbiased. This estimator performed well for a sample design with proportional allocation, but performed poorly for a sample design that included large strata that were lightly sampled. The logistic model-based estimator performed consistently well for all sample designs considered in terms of the extent of variability in estimation, although some modest bias was observed.
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Evidence-based medicine: is translating evidence into practice a solution to the cost-quality challenges facing medicine?
BACKGROUND: Evidence-based medicine (EBM) and practice guidelines have been embraced by increasing numbers of scholars, administrators, and medical journalists as an intellectually attractive solution to the dilemma of improving health care quality while reducing costs. However, certain factors have thus far limited the role that EBM might play in resolving cost-quality trade-offs. FACTORS FOR SUCCESS OF EBM RECOMMENDATIONS AND GUIDELINES: Beyond the quality of the guideline and the evidence base itself, critical factors for success include local clinician involvement, a unified or closed medical staff, protocols that minimize use of clinical judgment and that call for involvement of so-called physician extenders (such as nurse practitioners and physician assistants), and financial incentive. TROUBLESOME ISSUES RELATED TO COST-QUALITY TRADE-OFFS: Rationing presents many dilemmas, but for physicians one critical problem is determining what is the physician's responsibility. Is the physician to be the patient's advocate, or should the physician be the advocate of all patients (the patients' advocate)? How do we get physicians out of potentially conflicted roles? EBM guidelines are needed to help minimize the number of instances physicians are asked to ration care at the bedside. If the public can decide to share and limit resources--presumably based on shared priorities--physicians would have a basis to act as advocates for all patients. CONCLUSIONS: Although EBM alone is not a simple solution to the problems of increasing costs and public expectations, it can be an important source of input and information in relating the value of service and medical technology to public priorities.
Clinical Medicine↗
Teaching compassion and respect. Attending physicians' responses to problematic behaviors.
OBJECTIVE: To describe how and why attending physicians respond to learner behaviors that indicate negative attitudes toward patients. SETTING: Inpatient general internal medicine service of a university-affiliated public hospital. PARTICIPANTS: Four ward teams, each including an attending physician, a senior medicine resident, two interns, and up to three medical students. DESIGN: Teams were studied using participant observation of rounds (160 hours); in-depth semistructured interviews (n = 23); a structured task involving thinking aloud (n = 4, attending physicians); and patient chart review. Codes, themes, and hypotheses were identified from transcripts and field notes, and iteratively tested by blinded within-case and cross-case comparisons. MAIN RESULTS: Attending physicians identified three categories of potentially problematic behaviors: showing disrespect for patients, cutting corners, and outright hostility or rudeness. Attending physicians were rarely observed to respond to these problematic behaviors. When they did, they favored passive nonverbal gestures such as rigid posture, failing to smile, or remaining silent. Verbal responses included three techniques that avoided blaming learners: humor, referring to learners' self-interest, and medicalizing interpersonal issues. Attending physicians did not explicitly discuss attitudes, refer to moral or professional norms, "lay down the law," or call attention to their modeling, and rarely gave behavior-specific feedback. Reasons for not responding included lack of opportunity to observe interactions, sympathy for learner stress, and the unpleasantness, perceived ineffectiveness, and lack of professional reward for giving negative feedback. CONCLUSIONS: Because of uncertainty about appropriateness and effectiveness, attending physicians were reluctant to respond to perceived disrespect, uncaring, or hostility toward patients by members of their medical team. They tended to avoid, rationalize, or medicalize these behaviors, and to respond in ways that avoided moral language, did not address underlying attitudes, and left room for face-saving reinterpretations. Although these oblique techniques are sympathetically motivated, learners in stressful clinical environments may misinterpret, undervalue, or entirely fail to notice such subtle feedback.
Adult↗
Do physicians spend more time with non-English-speaking patients?
OBJECTIVE: To determine whether physicians at a general internal medicine clinic spend more time with non-English-speaking patients. DESIGN: A time-motion study comparing physician time spent with non-English-speaking patients and time spent with English-speaking patients during 5 months of observation. We also tested physicians' perceptions of their time use with a questionnaire. SETTING: Primary care internal medicine clinic at a county hospital. PATIENTS/PARTICIPANTS: One hundred sixty-six established clinic patients, of whom 57 were non-English speaking and 109 were English speaking, and 15 attending physicians and 8 third-year resident physicians. MEASUREMENTS AND MAIN RESULTS: Outcome measures included total patient time in clinic, wait for first nurse or physician contact, time in contact with the nurse or physician, physician time spent on the visit, and physician perceptions of time use with non-English-speaking patients. After adjustment for demographic and comorbidity variables, non-English-speaking and English-speaking patients did not differ on any time-motion variables, including physician time spent on the visit (26.0 vs 25.8 minutes). A significant number of clinic physicians believed that they spent more time during a visit with non-English-speaking patients (85.7%) and needed more time to address important issues during a visit (90. 4%), (both p <.01). Physicians did not perceive differences in the amount they accomplished during a visit with non-English-speaking patients. CONCLUSIONS: There were no differences in the time these physicians spent providing care to non-English-speaking patients and English-speaking patients. An important limitation of this study is that we were unable to measure quality of care provided or patients' satisfaction with their care. Physicians may believe that they are spending more time with non-English-speaking patients because of the challenges of language and cultural barriers.
Adult↗
Anxiety of Alzheimer's disease: prevalence, and comorbidity.
BACKGROUND: Anxiety may be associated with psychiatric morbidity, disability, increased health care utilization, and mortality in Alzheimer's disease (AD) patients as it is in the general adult population. However, the phenomenology of anxiety symptoms in AD and its relationship to dementia progression, comorbid depression, and the presence of other problematic behaviors have not yet been examined. METHOD: Data on anxiety symptoms and their coexistence with other factors were obtained in 523 community-dwelling AD patients through interviews with their caregivers and direct physical examination. The prevalence of anxiety symptoms and their association to patient depression, other behavioral problems, gender, and age was investigated. RESULTS: Anxiety symptoms were common, occurring in 70% of subjects. Anxiety symptoms were significantly correlated with ADL impairment and other behavioral disturbances, including wandering, sexual misconduct, hallucinations, verbal threats, and physical abuse. Comorbidity of anxiety-depression was also prevalent: 54% of the sample had both anxiety and depression symptoms. ADL impairment and problem behaviors were significantly associated with comorbidity; however, the latter association was explained entirely by the presence of anxiety. CONCLUSION: Anxiety symptoms were common and significantly related to ADL and additional neuropsychiatric problems in this sample. These results indicate the need for additional research into the phenomenology of anxiety and comorbid anxiety-depression in AD and for the development and investigation of effective assessment and treatment of anxiety in AD clinical practice.
Activities of Daily Living↗
Cognitive decline and Japanese culture in a cohort of older Japanese Americans in King County, WA: the Kame Project.
OBJECTIVES: The prevalence of Alzheimer's disease in studies of Japanese show generally lower rates when compared with those of Caucasians. We hypothesized that among a cohort of Japanese Americans lifestyle differences would act to modify progression of the Alzheimer pathologic process over many years, resulting in a slower cognitive decline among persons whose lifestyle is more characteristically Japanese. METHODS: One thousand, eight hundred and thirty-six nondemented persons were screened with the Cognitive Abilities Screening Instrument (CASI) at baseline, and 1,604 were rescreened 2 years later. Baseline questions included migration status, exposure to Japanese culture in early life and maintenance of such culture in adulthood, and other risk factors. Cognitive decline was defined as a 2-year loss of > or = 5.15 points/100 on CASI. RESULTS: In multivariable logistic regression, variables relating to reading, writing, and speaking Japanese, being born or having lived in Japan in early life, and having friends who are only/mostly Japanese were inversely associated with cognitive decline (odds ratios ranged between 0.28 and 0.64, with p < .05). Two factors emerged in a factor analysis of these variables. The strongest explained 49% of the variance for acculturation and loaded heavily on knowledge of the Japanese language and having spent one's early years in Japan. When this factor was dichotomized into the top 20th percentile, it predicted cognitive decline with an odds ratio of 0.12 (95% CI 0.03-0.49). DISCUSSION: These results show that a Japanese lifestyle may decrease the risk of expressing cognitive decline over a 2-year follow-up period. Lower cardiovascular disease rates among Japanese may also predispose them to lower rates of cognitive decline. The greater social support characteristic of Japanese culture as well as the role that Japanese language and culture may play in neural connectivity during brain development and/or in mental stimulation in adult life may also explain our findings.
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Validity and responsiveness of the Minimum Data Set.
OBJECTIVE: To determine the criterion validity and responsiveness to change over time of the Minimum Data Set (MDS). DESIGN: Cross sectional analysis comparing prospectively collected research data with MDS data reported from nursing homes on identical subjects. Longitudinal follow-up of subjects allowed for calculation of responsiveness to change over time. PARTICIPANTS: Subjects (n = 140) participating in epidemiological research on the natural history of Alzheimer's disease in the University of Washington Group Health Cooperative Alzheimer's Disease Patient Registry (ADPR) who entered nursing homes in Washington State from January 1990 through March 1996. MAIN OUTCOME MEASUREMENTS: Spearman's correlation coefficients to compare MDS cognitive performance scale scores with Mini-Mental State Examinations (MMSE), MDS behavior domain scores with ADPR Physician Behavior checklist scores, and MDS activities of daily living (ADL) functioning scores with Dementia Rating Scale scores for ADLs. Partial correlations were used to control for the number of days between MDS and ADPR assessments, age, and function in the other two MDS ratings of ADL, cognition, or behavior. We determined responsiveness by using the mean change in an effect size (ES) calculation for each domain of interest. RESULTS: MDS measures in all three domains were correlated modestly to the analogous ADPR research instruments, with correlation coefficients 0.45 for cognition, 0.50 for behavior, and 0.59 for ADL functioning. Controlling for age, time between ADPR and MDS assessments, and the MDS ratings of the other two MDS domains did not improve the correlations significantly. In a subgroup of 60 subjects followed for an average of 636 days, the Cognitive performance scale of the MDS had a slightly larger effect size (ES = 0.60) than the Folstein Mini-Mental Status Exam (ES = 0.39) used by the ADPR. However, the Dementia Rating Scale (ES = 0.77) used by the ADPR researchers reflected more change over time than the ADL domain of the MDS (ES = 0.02). The MDS behavior domain (ES = 0.058) was comparable to the research behavior checklist (ES = 0.065). CONCLUSIONS: These data demonstrate reasonable criterion validity of the MDS and the MMSE, ADL, and behavior rating scales and suggest that the MDS data is of adequate validity for research purposes in these areas. The MDS was less able to capture dementia-related change in ADLs in this population of patients with dementia even though the same nursing home staff completing the MDS often supplied the information for completing the research scales. As a result, the MDS may be limited as an outcome assessment instrument.
Activities of Daily Living↗
Clinico-neuropathological correlation of Alzheimer's disease in a community-based case series.
OBJECTIVES: Most clinico-neuropathological correlative studies of Alzheimer's Disease (AD) are based on research cohorts that are not necessarily generalizable to patients seen in the general medical community. In this study, we examine the accuracy of the criteria used in diagnosing AD in a community-based case series of patients with memory complaints. DESIGN AND PARTICIPANTS: Clinical and neuropathological diagnoses were obtained from 134 patients evaluated for dementia who subsequently underwent autopsy. SETTING: Subjects who exhibited new symptoms of dementia and were enrolled in the University of Washington/Group Health Cooperative Alzheimer's Disease Patient Registry were eligible for this study. MEASUREMENTS: Clinico-pathological correlation was performed using NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) and CERAD (Consortium to Establish a Registry for Alzheimer's Disease) criteria. RESULTS: Ninety-five of the 134 cases studied met CERAD neuropathological criteria for AD. The sensitivity of NINCDS-ADRDA "probable AD" was 83% (diagnosing AD correctly) and overall clinical diagnostic accuracy was 75%. However, there was a high rate of additional neuropathological findings. Only 34 of the 94 cases had pure AD on neuropathology, whereas the remainder frequently had coexisting vascular or Parkinson's disease lesions. CONCLUSIONS: This study of a large series of community-based incident dementia cases provides a way of judging the adequacy of currently available clinical diagnostic criteria. It also shows that co-existing neuropathological findings are common in community-based AD.
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Alzheimer's disease symptom severity in blacks and whites.
OBJECTIVE: In order to determine whether there are racial differences in Alzheimer's Disease (AD) symptom severity and vascular comorbidities, we compared African-American (black) and Caucasian (white) patients with AD from similar socioeconomic backgrounds at the time the disease was first recognized. DESIGN: Cross-sectional observational study from a population-based dementia registry. PARTICIPANTS: Patients were enrolled from an HMO base population of 23,000 persons more than age 60 in Seattle, Washington. This study examines 453 subjects with probable AD (38 blacks (mean age 76.5, SD 6.4), and 415 whites (mean age 79.7, SD 6.7)). MEASUREMENTS: Measured were patient demographics, age at onset of AD, AD symptom duration, Mini-Mental State Exam (MMSE) score, Blessed Dementia Rating Scale, presence of psychiatric symptoms, and vascular comorbidities. RESULTS: Blacks had significantly lower mean cognitive scores (MMSE = 17.2, SD 5.6) compared with whites (MMSE = 20.2, SD 5.2, unpaired t test P < .01). The significant racial difference in MMSE scores persisted after controlling for education, duration of AD symptoms, age, and ADL impairment. Blacks and whites did not differ significantly regarding gender distribution, education level, income, or percent with early age of onset of AD. No statistically significant race-related differences were found in impairments in activities of daily living or symptoms of paranoia, hallucinations, or agitation. Blacks had significantly higher rates of hypertension (56%) compared with whites (34%) (Fisher's exact test, P = .013), but the rates of stroke and ischemic heart disease were similar. CONCLUSIONS: Despite uniform detection methods and controlling for reported duration of dementia symptoms, measured cognitive impairment is significantly more severe when AD is recognized in blacks compared with whites. The significantly higher prevalence of hypertension among black AD cases was not associated with excess cerebrovascular disease comorbidity. This study highlights a need for normative measurements of cognitive function in minority AD groups in order to distinguish differential cognitive symptom severity from possible measurement bias.
Activities of Daily Living↗
Characteristics of sleep disturbance in community-dwelling Alzheimer's disease patients.
This study examined the frequency, predictors, and impact of sleep problems in a population-based sample of 205 Alzheimer's disease (AD) patients. Sleeping more than usual and early morning awakenings were the most common sleep problems reported but were the least disturbing behaviors for caregivers. Night-time awakenings were less common but were most disturbing to caregivers. Using logistic regression analyses, the factors most strongly associated with night awakenings among patients were male gender, greater memory problems, and decreased functional status. Patient depression increased the risk for caregivers to rate patient sleep problems as more disturbing overall. Cluster analyses revealed three characteristic groups of patients who awakened caregivers: one group was inactive during the day but had few other behavior problems; one group had increased levels of fearfulness, fidgeting, and occasional sadness; and the third group had multiple behavior problems, including frequent episodes of sadness, fearfulness, inactivity, fidgeting, and hallucinations. These findings indicate that the nature of sleep problems in AD is multifaceted; future research on the occurrence and treatment of sleep disturbance in dementia patients should consider the patterns of individual differences that may influence its development.
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Drug-induced cognition disorders in the elderly: incidence, prevention and management.
The aetiology of cognitive impairment is multifactorial; however, drugs are an important cause of delirium and dementia. Several factors may increase the risk of drug-induced cognition disorders in the elderly including imbalances in neurotransmitters (e.g. acetylcholine), age-related alterations in pharmacokinetics and pharmacodynamics, and high levels of medication use. Nearly any drug can cause cognitive impairment in susceptible individuals; however, certain classes are more commonly implicated. Benzodiazepines, opioids, anticholinergics, and tricyclic antidepressants are probably the worst offenders. Older antihypertensive agents (reserpine, clonidine) have negative effects on cognition; however, large clinical trials in the elderly indicate that commonly used agents [e.g. thiazide diuretics, calcium antagonists (amiodipine, diltiazem), ACE inhibitors (captopril, enalapril) and beta-blockers (atenolol)] have minimal effects on cognition. Newer antidepressants such as selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) and reversible inhibitors of monoamine oxidase A have not been shown to have negative effects on cognition. Although some drugs have shown low risk for causing cognition disorders in research studies, risk may be increased in frail older adults taking several medications and each case should be reviewed carefully. Identification of drug-induced cognitive impairment is crucial to early detection and resolution of symptoms. Preventive strategies directed at avoiding high risk medications when possible, appropriately adjusting doses based on age-related changes and close follow-up may prevent these conditions.
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What's new in Alzheimer's disease treatment? Reasons for optimism about future pharmacologic options.
There is reason for optimism about future treatment options for Alzheimer's disease, despite uncertainties about which subgroups of patients will respond to treatment, the magnitude of therapeutic effects, the duration of benefit, and the long-term outcomes from disease-modifying agents. Because Alzheimer's disease is a heterogeneous disorder, the range of treatment responses likely will remain variable. The decision to initiate treatment must be individualized to the therapeutic goals of the patient and his or her caregiver. Advances in the understanding of the pathogenesis of Alzheimer's disease have led to new treatment strategies. Augmentation of cholinergic function through the use of acetylcholinesterase inhibitors with favorable side-effect profiles (e.g., donepezil, possibly metrifonate) can create the potential for improved memory and cognition. Antiinflammatory drugs, estrogen, alpha-tocopherol, selegiline, and ginkgo biloba are the subject of ongoing clinical trials to determine their effectiveness in Alzheimer's disease. Future treatment strategies will likely include a combination of acetylcholinesterase inhibitors and disease-modifying agents. A greater understanding of the pathogenesis of Alzheimer's disease may lead to the development of new neuroprotective agents. The long-term human and social costs, as well as potential benefits, of prolonging the natural course of the disease can only become evident with study of these agents in years to come.
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The cognitive abilities screening instrument (CASI): data from a cohort of 2524 cognitively intact elderly.
OBJECTIVES: To describe the effects of age and education for the Cognitive Abilities Screening Instrument (CASI), a 25-item test of cognitive function. DESIGN: Cross-sectional descriptive study of the initial enrollment in a community-based prospective cohort study. PARTICIPANTS: A total of 2524 cognitively intact older adults over age 65 who were members of a major health maintenance organization, and who consented to participate in a longitudinal study. MEASUREMENTS: Summary scores for the CASI are given in the form of mean, median and percentile distributions specific for age and educational level. RESULTS: Based upon maximum likelihood analyses, age and education were significant (p<0.0001) predictors of total CASI score. Increased age and lower education were associated with a lower CASI score, as well as an increased spread in score distribution. Gender was also significantly related (p<0.01) to total CASI, with women having a slightly higher distribution of scores. Mean total scores ranged from CASI=82.2 (SD=9.0) in subjects aged 90-95 who had less than a high school degree to CASI=94.8 (SD=3. 8) in subjects aged 65-69 with at least a high school education. CONCLUSIONS: Like most cognitive screening instruments, performance on the CASI in non-demented persons is influenced by age and education. The reference values for 5-year age categories described in this article should be useful for clinicians and research investigators when using the CASI as a measure of cognitive function.
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Breast carcinoma tumor characteristics in black and white women.
BACKGROUND: A significant disparity in mortality rates exists between black and white patients with breast carcinoma. This study was designed to compare breast carcinoma tumor characteristics by race and to examine the possible reasons for these differences. METHODS: Female patients with an initial diagnosis of breast carcinoma between January 1, 1985 and December 31, 1993 were selected from the Yale-New Haven Hospital Tumor Registry for this retrospective cohort study. All black patients were eligible and white patients were selected randomly and matched to each black patient by year of diagnosis. Data were gathered from multiple sources including the hospital, the Connecticut Tumor Registry, and the U. S. Census. All pathology specimens were reviewed at Yale-New Haven Hospital. RESULTS: The final cohort had 100 black and 300 white patients. The black patients tended to be younger than white patients at the time of diagnosis (mean age 55 years vs. 60 years; P = 0.001). A significant racial difference was noted in eight tumor characteristics: stage, size of the tumor, lymph node status, presence of necrosis, vascular/lymphatic invasion, ductal carcinoma in situ, perineural invasion, and progesterone receptor status. Although income, medical insurance coverage, and method of tumor detection explained some pathology differences, black patients still were more likely to have necrosis and a larger tumor size, even after adjustment. CONCLUSIONS: Black patients with breast carcinoma tend to be diagnosed at a younger age and in a few important respects have different tumor characteristics compared with white patients, even after controlling for income, medical insurance coverage, and method of tumor detection after screening mammography. These differences may have etiologic and clinical implications.
Adult↗
Internet access to patients' records.
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Computer Communication Networks↗
New drug treatments for Alzheimer disease.
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Alzheimer Disease↗