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D A Bennett

Publications and source records attributed to D A Bennett.

At least 91 records · Page 5Linked to original sources
PubMed1999

Dimensionality of parkinsonian signs in aging and Alzheimer's disease.

BACKGROUND: Parkinsonian signs are commonly found on the neurologic examination of older persons and are associated with morbidity and mortality. The extent to which parkinsonian signs in aging and Alzheimer's disease cluster in groups typical of Parkinson's disease has not been investigated previously. METHODS: The motor portion of the Unified Parkinson's Disease Rating Scale (UPDRS), or a version with minor modifications, was administered to more than 2,800 persons in three cohorts: (a) 637 older persons with a wide range of neurologic conditions participating in the Chicago Health and Aging Project, a study of common health problems of a random sample of older persons from a geographically defined biracial community population; (b) 638 relatively healthy and highly educated older persons from 25 Catholic religious communities participating in the Religious Orders Study, a longitudinal clinical-pathologic study of aging; and (c) 1,546 older persons undergoing evaluation for possible dementia at the Rush Alzheimer's Disease Center, an urban, tertiary care center that evaluates persons for possible dementia. Separate factor analyses were performed on each data set. Additional analyses examined the factor structure in subsets by gender and race. RESULTS: A similar grouping of items emerged in each cohort and did not differ substantially by gender or race. The factors corresponded closely with the traditional grouping of parkinsonian signs into bradykinesia, gait disturbance, rigidity, and tremor. CONCLUSIONS: The grouping of parkinsonian signs is consistent in diverse samples of older persons and does not vary substantially across gender or race. The results provide an empirical basis for summarizing the principal motoric manifestations of parkinsonism.

Aged↗
PubMed1999

Cognitive activity in older persons from a geographically defined population.

Patterns of cognitive activity, and their relation to cognitive function, were examined in a geographically defined, biracial population of persons aged 65 years and older. Persons (N = 6,162) were given cognitive performance tests and interviewed about their participation in common cognitive activities, like reading a newspaper. Overall, more frequent participation in cognitive activities was associated with younger age, more education, higher family income, female gender, and White race; participation in activities judged to be more cognitively intense was not strongly related to age, but was associated with more education, higher family income, male gender, and White race. Substantial heterogeneity in activity patterns remained after accounting for demographic factors, however. In an analysis controlling for demographic variables, level of cognitive function on performance tests was positively related to composite measures of the frequency and intensity of cognitive activity. Longitudinal studies are needed to assess the relation of cognitive activity patterns to stability and change in cognitive function in older persons.

Aged↗
PubMed1998

Object decision priming in Alzheimer's disease.

Priming for line drawings of real and nonreal objects was examined in an object decision task for 16 patients with Alzheimer's disease (AD) and 16 normal elderly control (NC) participants. In two study phases, participants decided if objects were real or nonreal. In an implicit test phase, real/nonreal decisions were made for studied and unstudied objects, and priming was measured as the difference in decision speed or accuracy between studied and unstudied objects. In an explicit test phase, yes/no recognition was measured for real and nonreal objects. AD patients had impaired explicit memory for real and nonreal objects and intact repetition priming for real objects. By the latency measure, both AD and NC groups showed priming for nonreal objects but in opposite ways. Classification decisions about studied relative to nonstudied nonreal objects were slower for the AD patients, whereas such decisions were faster for the NC participants. Classification decisions of both groups were less accurate for repeated nonreal objects. These results support the claim that AD patients with mild cognitive impairment show normal perceptual priming. The AD inhibition for studied nonreal objects is discussed in terms of the decision conflict that occurs when recollection of source is not available to counter the influence of familiarity.

Aged↗
PubMed1998

Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease.

Oxidative stress may play a role in neurologic disease. The present study examined the relation between use of vitamin E and vitamin C and incident Alzheimer disease in a prospective study of 633 persons 65 years and older. A stratified random sample was selected from a disease-free population. At baseline, all vitamin supplements taken in the previous 2 weeks were identified by direct inspection. After an average follow-up period of 4.3 years, 91 of the sample participants with vitamin information met accepted criteria for the clinical diagnosis of Alzheimer disease. None of the 27 vitamin E supplement users had Alzheimer disease compared with 3.9 predicted based on the crude observed incidence among nonusers (p = 0.04) and 2.5 predicted based on age, sex, years of education, and length of follow-up interval (p = 0.23). None of the 23 vitamin C supplement users had Alzheimer disease compared with 3.3 predicted based on the crude observed incidence among nonusers (p = 0.10) and 3.2 predicted adjusted for age, sex, education, and follow-up interval (p = 0.04). There was no relation between Alzheimer disease and use of multivitamins. These data suggest that use of the higher-dose vitamin E and vitamin C supplements may lower the risk of Alzheimer disease.

Aged↗
PubMed1998

Neuropharmacology of St. John's Wort (Hypericum).

OBJECTIVE: To review preclinical information related to possible antidepressant mechanism(s) of action of St. John's wort in order to address the issue of whether its purported clinical effectiveness has a rational pharmacologic basis. DATA SOURCES: Primary and review articles were identified by a MEDLINE search (1966-January 1998) and through secondary sources. Many of the original German articles had English abstracts, but where necessary, German articles were translated into English. The results of a new screen of hypericin activity at receptor and uptake sites are summarized. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from the data sources were evaluated and all information deemed relevant was included in this review. DATA SYNTHESIS: The neuropharmacology of St. John's wort has been examined in only a few studies. A mechanism similar to that of the synthetic antidepressants, such as the selective serotonin-reuptake inhibitors or monoamine oxidase (MAO) inhibitors, might play a role, but other mechanisms are possible. CONCLUSIONS: Hypericum extracts have only weak activity in assays related to mechanisms of the synthetic antidepressants, that is, inhibition of MAO, catechol O-methyltransferase, or serotonin reuptake. It has been postulated that the clinical efficacy of St. John's wort could be attributable to the combined contribution of several mechanisms, each one too weak by itself to account for the overall effect. The recent demonstration of a significant affinity of hypericin for sigma receptors presents new possibilities for consideration.

Animals↗
PubMed1997

Chlamydia pneumoniae as a new source of infectious outbreaks in nursing homes.

OBJECTIVE: To determine the extent and severity of illness and mode of transmission of Chlamydia pneumoniae infection in 3 nursing home outbreaks. DESIGN AND SETTING: Retrospective cohort study in 3 nursing homes in Ontario from September to November 1994. SUBJECTS: A total of 549 residents and 65 staff members. MAIN OUTCOME MEASURES: Morbidity and mortality were determined by a review of disease surveillance forms, residents' charts, and a self-administered questionnaire to staff. Single and paired serum samples for C pneumoniae serological testing and nasopharyngeal swabs for C pneumoniae culture were collected, and direct fluorescent antibody assays were performed to confirm C pneumoniae infection. RESULTS: The attack rates for confirmed and suspected cases combined were 68%, 46%, and 44% among residents in nursing homes A, B, and C, respectively, and 34% among nursing home C staff. A total of 16 cases of pneumonia confirmed by chest x-ray and 6 deaths were identified. The spectrum of illness among nursing home C residents included a new cough in 58 (100%), fever in 37 (64%), sore throat in 14 (24%), and hoarseness in 8 (14%). Staff members at nursing home C were more likely to report hoarseness (P<.001) and sore throat (P<.001). Residents who smoked had onset of illness earlier than nonsmokers (P=.007), which perhaps is related to airborne transmission in a designated smoking room. CONCLUSIONS: Chlamydia pneumoniae caused serious morbidity and mortality among residents and morbidity among staff; C pneumoniae is an important cause of respiratory disease outbreaks in nursing homes, and diagnostic tests must be readily available for early recognition of C pneumoniae infections.

Aged↗
PubMed1997

Apolipoprotein E epsilon4 and incidence of Alzheimer disease in a community population of older persons.

OBJECTIVE: To examine the relation between apolipoprotein E status and risk of Alzheimer disease (AD) in a defined population and estimate the fraction of incident AD attributable to the epsilon4 allele. DESIGN: Community-based cohort study. SETTING: East Boston, Mass. PARTICIPANTS: A random sample of 578 community residents aged 65 years and older free of AD. MAIN OUTCOME MEASURE: Clinical diagnosis of AD by uniform, structured evaluation. RESULTS: The increased risk of AD associated with the presence of the epsilon4 allele was less than that found in most family and case-control studies. Persons with the epsilon4/epsilon4 or epsilon3/epsilon4 genotypes had 2.27 (95% confidence interval, 1.06-4.89) times the risk of incident disease compared with those with the epsilon3/epsilon3 genotype. The epsilon4 allele accounted for a fairly small fraction of the incidence of AD; if the allele did not exist or had no effect on disease risk, the incidence would be reduced by only 13.7%. The effect of the epsilon4 allele on risk of AD did not appear to vary with age. CONCLUSIONS: The apolipoprotein E epsilon4 allele is an important genetic risk factor for AD but accounts for a fairly small fraction of disease occurrence in this population-based study. Continued efforts to identify other environmental and genetic risk factors are warranted.

Aged↗
PubMed1997

Metric properties of nurses' ratings of parkinsonian signs with a modified Unified Parkinson's Disease Rating Scale.

We evaluated the ability of nurse clinicians to assess parkinsonian signs in older persons with a modified version of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS). After completing a structured training protocol, three nurse clinicians and a neurologist with expertise in movement disorders administered a modified UPDRS to 75 older persons. The nurses repeated the assessment about 3 weeks later. Inter-rater agreement and short-term temporal stability were estimated for each item, the total modified UPDRS score, and for summary measures of bradykinesia, postural reflex impairment, rigidity, and tremor, and a global parkinsonian sign score. We performed our assessment in Catholic religious communities in the Chicago area, using consecutive subjects at four communities participating in the Religious Orders Study, a longitudinal, clinical-pathologic study of older persons. Our results showed that nurses were not a significant source of variability, with intraclass correlations exceeding 0.97 for all items, and they showed good to excellent agreement with the neurologist for most modified UPDRS items. Correlations between nurses and neurologist exceeded 0.90 for the total modified UPDRS, ranged from 0.76 to 0.95 for the four parkinsonian domain scores, and exceeded 0.90 for the global parkinsonian sign score. Nurses showed fair to good agreement with themselves over the 3-week interval for most modified UPDRS items. Correlations over the 3-week interval exceeded 0.90 for the total modified UPDRS score, ranged from 0.70 to 0.95 for the four domain scores, and exceeded 0.90 for the global parkinsonian sign score. Ratings of parkinsonian signs by nurse clinicians corresponded closely to those of a neurologist with expertise in movement disorders and showed good inter-rater agreement and temporal stability. With appropriate training, nurse clinicians can reliably administer the modified UPDRS.

Aged↗
PubMed1997

Why Alzheimer's disease is a women's health issue.

Alzheimer's disease is not typically included on the list of important women's health issues. Yet Alzheimer's disease is indeed a women's disease. Not only do more women than men have Alzheimer's disease, but women also provide a disproportionate amount of the informal community care for people with the disease. The prevalence of Alzheimer's disease increases dramatically with age and is highest among those 85 years of age and older. Women make up 72% of the US population over age 85 and, therefore, are the group most affected by the disease. By the year 2050, the number of people with Alzheimer's disease will more than double from approximately 4 million to 10 million, and 70% of these people will be age 85 or older. Although the symptoms and course of Alzheimer's disease may be similar in women and men, social and economic factors may produce a greater burden of disease among women, particularly with respect to the types and quality of health care services they receive, because women generally have the most limited social and financial resources. As the population ages, typical patients with Alzheimer's disease will be much older, frailer, and will have more functional impairments and chronic diseases than the patients most physicians see today. Future research needs to focus on identifying modifiable risk factors and effective treatments for Alzheimer's disease, and on determining the appropriate types of community-based and institutional services required to care for those with the illness as well as their families.

Aged↗
PubMed1996

Prevalence of parkinsonian signs and associated mortality in a community population of older people.

BACKGROUND: Older people frequently have signs of parkinsonism, but information about the prevalence of parkinsonism and mortality among those with the condition in the community is limited. METHODS: A stratified random sample of 467 residents of East Boston, Massachusetts, 65 years of age or older, were given structured neurologic examinations. Using uniform, specified combinations of parkinsonian signs, we estimated the prevalence of four categories of signs--bradykinesia, gait disturbance, rigidity, and tremor--and of parkinsonism, defined as the presence of two or more categories. We did not study Parkinson's disease because it could not be distinguished from other conditions that can cause parkinsonism. Proportional-hazards models were used to compare the risk of death among people with and those without parkinsonism. RESULTS: One hundred fifty-nine persons had parkinsonism, 301 did not, and 7 could not be classified. The overall prevalence estimates were 14.9 percent for people 65 to 74 years of age, 29.5 percent for those 75 to 84, and 52.4 percent for those 85 and older. With a mean follow-up period of 9.2 years, 124 persons with parkinsonism (78 percent) and 146 persons without (49 percent) died. Adjusted for age and sex, the overall risk of death among people with parkinsonism was 2.0 (95 percent confidence interval, 1.6 to 2.6) times that among people without. Among people with parkinsonism, the presence of gait disturbance was associated with an increased risk of death. CONCLUSIONS: Parkinsonism is very common among people over the age of 65, and its prevalence increases markedly with age. Parkinsonism is associated with a twofold increase in the risk of death, which is strongly related to the presence of a gait disturbance.

Age Distribution↗
PubMed1996

Familial Creutzfeldt-Jakob disease with a five-repeat octapeptide insert mutation.

We report a familial form of Creutzfeldt-Jakob disease, associated with a unique insert mutation of the PRNP gene in an American family of Ukrainian origin. Ten family members exhibited early age at onset and long-duration illnesses characterized primarily by personality changes, cognitive impairment, and spasticity. The proband, presenting at age 42 years, exhibited a fairly stable, nonprogressive course over 7 years, followed by precipitous decline and death in the eighth year. Other affected family members exhibited marked clinical heterogeneity. Each tested affected member had an insert mutation consisting of five extra octapeptide repeats between codons 51 and 91 of the PRNP gene on chromosome 20. Examination of two autopsy cases showed classic spongiform change, neuronal loss and astrocytosis in one case, and minimal pathologic abnormality in the other case. This report documents a new insert mutation of the PRNP gene, and confirms the early age of onset, characteristically prolonged clinical course, and clinical and pathologic heterogeneity seen in such mutations.

Adult↗
PubMed1994

Alzheimer's disease: a comprehensive approach to patient management.

Despite advances in our understanding of Alzheimer's disease (AD), the diagnosis is still made from the clinical history and assessment of cognitive function. The physical, neurologic exam, and laboratory testing help you look for any other condition that may be contributing to the dementia. Once the diagnosis is made, your role becomes that of a resource to the patient and family. Drug therapies may be needed to manage AD-related depression, sleep/wake cycle alterations, and aggressive behaviors. Some patients with mild to moderate cognitive deficits may be candidates for tacrine or enrollment in clinical trials of experimental therapies. Community resources, advocacy, and driving safety should be discussed with each patient and his/her family.

Aged↗
PubMed1992

Clinical correlates of high signal lesions on magnetic resonance imaging in Alzheimer's disease.

The pathophysiology and clinical significance of high signal lesions, visualized on magnetic resonance imaging (MRI) in patients with Alzheimer's disease (AD), remain controversial. Since they are known to correlate with vascular disease and vascular risk factors, we reviewed the clinical correlates of periventricular high signal (PVH) and subcortical white matter lesions (WML) in a sample of 106 patients with probable AD, excluding persons with treated vascular risk factors or symptomatic cerebrovascular and cardiovascular disease. Grade 2 PVH were seen in 26 (25%) and scattered WML were identified in 29 (18%). PHV were associated with advancing age and gait disturbance. WML were associated with gait disturbance and incontinence. Neither radiologic finding was related to dementia severity. The findings suggest that these lesions are common in patients with AD even when those with evidence of cerebrovascular disease are excluded; their presence, therefore, should not preclude a diagnosis of AD. Additionally, the data suggest that HSL on MRI may be one of many risk factors associated with functional disability in persons with probable AD.

Aged↗
PubMed1992

Alzheimer's disease.

Alzheimer's disease is one of the most severe and most common chronic diseases of older persons. Because occurrence of the disease is strongly related to age, its public health impact is likely to continue to increase as the population ages. As with many other diseases, a diagnosis of Alzheimer's disease is made through a combination of clinical history, physical, and neurologic examination, and laboratory evaluation. Because the dominant feature of this disease is its effect on cognition, its diagnosis requires careful evaluation of cognitive function usually with formal neuropsychological performance testing. Clinical evaluation of persons for Alzheimer's disease has four objectives: (1) to determine as accurately as possible if the person has dementia; (2) if dementia is present, to determine whether its presentation and course are consistent with a diagnosis of Alzheimer's disease; (3) to assess evidence for any alternate diagnoses, especially if the presentation and course are atypical for Alzheimer's disease; and (4) to evaluate evidence of other, coexisting, diseases that may contribute to the dementia, with strong emphasis on conditions that might respond to treatment. There is no reliable antemortem diagnostic test for Alzheimer's disease; the main purpose of laboratory testing is to identify other conditions that might cause or exacerbate dementia. Pathologically, Alzheimer's disease is characterized by the presence of two lesions on microscopic examination of the brain: neuritic plaques and neurofibrillary tangles. Both lesions can be seen in the brains of older persons without dementia. However, they are found in greater numbers in the neocortex and hippocampus with Alzheimer's disease. Caring for patients with Alzheimer's disease is demanding and requires compassion and skills that go beyond the choices among sophisticated and effective therapies that characterize much of modern medical practice. The current lack of effective pharmacotherapy for cognitive dysfunction in Alzheimer's disease should not obscure that there are many areas in which intervention can improve quality of life for both the patient and the caregiver. Achieving success in these areas typically requires that the physician work effectively with providers of many other medical and nonmedical services. Community resources, advocacy, behavior management, and experimental therapies and procedures, should be discussed with the family of each patient. In addition, persons with mild disease should be promptly informed of their diagnosis in order to obtain their wishes regarding life prolonging measures and extended care options.

Aging↗
PubMed1991

Anxiolytic properties of certain annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones.

Modification of the benzodiazepine (BZ) receptor binding template 2-aryl[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one by replacement of the annelated benzene ring with various alicyclic and heterocyclic moieties led to novel structures with potent BZ receptor binding affinity. High affinity was found in some cycloalkyl-annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones and in some 7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]triazolo[1,5-c]pyrimidin- 5(6H)-ones, in which the degree of activity was strongly dependent on the N-substituent in the 9-position. Nine compounds with BZ receptor IC50 binding affinity values equal or superior to diazepam were evaluated in secondary screening. One of these, 9-benzyl-2-phenyl-7,8,9,10-tetrahydropyrido[3,4-e] [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one, showed good activity in rats as a potential anxiolytic agent without sedative liability. However, it increased the rotorod deficit produced by ethanol at anxiolytic doses, an indication of alcohol interaction. Thus, none of the compounds showed an advantage over CGS 9896 (Yokoyama et al. J. Med. Chem. 1982, 25, 337-339), which is free of sedative and alcohol interaction potential as measured by the test procedures described.

Aggression↗