Biomedical subjects

R Mayeux

Publications and source records attributed to R Mayeux.

At least 145 records · Page 8Linked to original sources

PubMed1993

Safety and efficacy of oral physostigmine in the treatment of Alzheimer disease.

Results of therapeutic trials with physostigmine in the treatment of Alzheimer disease (AD) have been inconsistent and controversy persists concerning safety and efficacy. In a double-blind, placebo-controlled, crossover study, patients received 6 weeks of oral physostigmine (OP) and placebo in random order. Twenty-nine patients with AD received as much as 16 mg/day of OP and were assessed with neuropsychological and functional measures. No significant cardiac side effects were noted, though other systemic adverse effects were noted, requiring dose reduction in four patients. There was a slight but significant improvement (12%) in performance on the selective reminding test with physostigmine and the memory performance was correlated with dosage. This improvement compares favorably with the 15% decrease in scores seen in an untreated comparison cohort followed for an equivalent time period. There was a trend toward an improvement in communication and a reduction in memory complaint. These results suggest that oral physostigmine is safe and may improve memory in AD.

Administration, Oral↗

PubMed1993

The effect of zidovudine on neuropsychiatric measures in HIV-infected men.

The authors examined the effects of zidovudine on neuropsychiatric measures, at three assessment points separated by 6 months, in 25 HIV-positive men who took zidovudine for at least 6 months and a comparison group of 25 HIV-positive men with similar CD4+ T cell counts who had never taken zidovudine. Zidovudine had no statistically significant effect except for a slight improvement in Global Assessment of Functioning scale score. In this small group of subjects there was little benefit but also little evidence of CNS toxicity from zidovudine.

CD4-Positive T-Lymphocytes↗

PubMed1993

Subtle extrapyramidal signs can predict the development of dementia in elderly individuals.

To assess the significance of mild extrapyramidal signs (EPSs) in aging, we prospectively followed 228 elderly individuals without dementia or major neurologic disease at baseline. Seventy-three (32%) showed mild idiopathic EPSs at baseline assessment and 32 (14%) of these 228 individuals met NINCDS-ADRDA criteria for probable or possible Alzheimer's disease on follow-up. While none of these individuals developed Parkinson's disease, those with more than one EPS at baseline were significantly more likely to become demented during follow-up than were those with one or no EPS, an association not confounded by age, education, or gender. Individuals with more than one EPS and with cognitive impairment (CI) at baseline were at highest risk for dementia. EPSs were also independently associated with incident dementia in the absence of CI at baseline. We conclude that mild EPSs are a significant predictor of dementia in elderly individuals.

Aged↗

PubMed1993

Mortality risks in gay men with human immunodeficiency virus infection and cognitive impairment.

We obtained data from 111 gay men who entered a longitudinal study of the natural history of human immunodeficiency virus (HIV) without clinical evidence of acquired immunodeficiency syndrome (AIDS), and examined them regularly over a 36-month period. Using a Cox proportional-hazard regression model to compare cumulative risk of mortality in subjects with and without cognitive impairment and several putative risk factors present at baseline, we found that the mortality risk ratio (RR) associated with poor neuropsychologic test performance was significantly increased (RR = 2.9; 95% confidence interval [CI], 1.1 to 7.8), and increased further (RR = 4.1; 95% CI, 1.3 to 12.5) when adjusted for other factors associated with mortality (a history of a disturbance in movement or gait, CD4-lymphocyte and red blood-cell counts, and age). A significant increase in symptoms related to cognitive impairment and gait, a decline in neuropsychologic test performance, and declines in CD4-lymphocyte and red-cell counts occurred over the study period. A second model was constructed to adjust for changes in CD4-lymphocyte and red-cell counts, age, medical stage, and motor symptoms over the study period, but the mortality RR for poor neuropsychologic test performance at baseline changed very little (RR = 4.7; 95% CI, 1.5 to 14.9). We conclude that the presence of cognitive impairment, manifest by poor neuropsychologic test performance in both asymptomatic and symptomatic gay men with HIV infection, is associated with a significantly increased risk of death. This effect progresses in parallel with the immunologic and systemic effects of HIV.

Adult↗

PubMed1993

Antecedent clinical features associated with dementia in Parkinson's disease.

In a prospective cohort study, we examined clinical features in 250 nondemented patients with idiopathic Parkinson's disease (PD) and then evaluated their association with incident dementia during 5 years of follow-up. Seventy-four of the patients became demented. Odds ratios for incident dementia with PD were increased for the following: being older than 70 years of age (2.7; 1.4 to 5.5), having a PD rating scale score greater than 25 (3.0; 1.5 to 6.2), being depressed (2.7; 1.5 to 6.6), being confused or psychotic on levodopa (3.3; 1.3 to 8.7), or having facial masking as a presenting sign (6.1; 1.4 to 26.9).

Aged↗

PubMed1993

Patterns of neuropsychological performance in Alzheimer's disease patients with and without extrapyramidal signs.

We investigated the relationship between extrapyramidal signs (EPS) and the cognitive function in 90 patients meeting NINCDS-ADRDA criteria for probable Alzheimer's disease (AD) by dividing them into those showing no evidence of EPS and those showing at least one EPS on the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological tests of verbal memory, orientation, abstract reasoning, language, and construction. Patients with EPS were significantly more impaired than patients without EPS on tests of short-term learning and memory, orientation, naming, verbal fluency, and construction, but not on tests of long-term memory, abstract reasoning, or verbal comprehension. These results could not be explained by any differences in age, education, or disease duration between the groups. Since this pattern of neuropsychological impairment resembles that of patients with Parkinson's disease and other EPS syndromes, we hypothesize that EPS are associated with neuropathologic and neuropsychological changes that are superimposed over the classic features of AD.

Aged↗

PubMed1993

Regional cerebral blood flow in mood disorders. II. Comparison of major depression and Alzheimer's disease.

We contrasted regional cerebral blood flow in matched groups of 30 patients with major depression, 30 patients with Alzheimer's disease and 30 normal controls using the 133Xe inhalation technique. Whereas both the depressed and Alzheimer's disease groups had markedly reduced global cortical blood flow, the Scaled Subprofile Model, developed to identify abnormalities in regional networks, indicated that they had distinct topographic profiles. Previous findings of an abnormal regional network in major depression were unaltered by the inclusion of Alzheimer's disease patients in the analysis. Alzheimer's disease was associated with a distinct parietotemporal deficit and the degree of this abnormality strongly covaried with cognitive impairment. Alzheimer's disease patients also had abnormal manifestation of three other regional networks. We illustrate a method for distinguishing when a disease imposes a new pattern of interactions among brain regions and when a disease alters the expression of regional patterns characteristic of normal functioning.

Aged↗

PubMed1992

A prospective controlled study of magnetic resonance imaging of the brain in gay men and parenteral drug users with human immunodeficiency virus infection.

To detect the earliest structural changes in the brain in human immunodeficiency virus (HIV) infection, 118 gay men and 115 parenteral drug users enrolled in a study of the natural history of HIV infection underwent magnetic resonance imaging evaluations. Routine T2-weighted and heavily T2-weighted scans for quantification of brain water were obtained, blinded to HIV serostatus. Atrophy and foci of increased signal did not correlate with any medical, immunologic, neurologic, or neuropsychologic parameters in the group as a whole, or in the gay men or parenteral drug user subgroups. Three subjects had progressive multifocal leukoencephalopathy and one had central nervous system lymphoma. In a subgroup in whom intracranial water percent was calculated, correlations were found with CD4 counts and CD4/CD8 ratios. We conclude that standard magnetic resonance imaging of the brain does not differentiate asymptomatic and mildly symptomatic HIV-positive individuals from HIV-negative individuals, regardless of risk group. However, intracranial water percent may distinguish HIV-positive from HIV-negative individuals because it correlates with raw CD4 counts and CD4/CD8 ratios.

Adolescent↗

PubMed1992

An estimate of the incidence of depression in idiopathic Parkinson's disease.

Estimates of the prevalence of depression in idiopathic Parkinson's disease vary, but have been greater than in most comparison groups. In a survey of patients with Parkinson's disease (N = 339), the prevalence of depression was 47%. A total of 326 cases were reviewed to estimate the incidence of depression from September 30, 1984, to July 31, 1989. Assessments of depression during both the prevalent and the incident periods were noted in 258 cases. There was no history of depression in 129 cases, and nine new cases occurred. The incidence rate was 1.86% per year and the cumulative risk was 8.6%. Published estimates of the incidence of depression in the general population are few. In one study, the annual incidence of depression in individuals older than 40 years was 0.17%. In another, the incidence of depression in individuals older than 50 years was 0.14% for men and 0.29% for women. Although our retrospective study probably underdiagnoses depression, the incidence of depression is increased in Parkinson's disease.

Aged↗

PubMed1992

The Columbia University Scale for Psychopathology in Alzheimer's disease.

The Columbia University Scale for Psychopathology in Alzheimer's disease is a new screening instrument developed for use by clinicians or trained lay interviewers. Interrater reliability was established between a psychiatrist and a lay interviewer in 20 patients. In an independent sample of 91 outpatients with very mild to moderate probable Alzheimer's disease, caregiver informants reported that depressed mood was common (46.2%) but rarely persistent (2.2%), and that sleep disturbance occurred frequently (41.8%) but was never severe (0%). There were significant but weak associations between the presence of specific subtypes of delusions and severity of dementia. Although a variety of delusional symptoms were reported, they were frequently transient and patients often accepted the truth if corrected by the caregiver. As a result, few patients met broad or narrow operational criteria used to define delusions. Prior studies may have overestimated the prevalence of psychotic features in Alzheimer's disease by not employing standard definitional criteria. The findings also indicate that new methodology such as that employed in this instrument needs to be evaluated more widely.

Aged↗

PubMed1992

Diagnosis of dementia in a heterogeneous population. Development of a neuropsychological paradigm-based diagnosis of dementia and quantified correction for the effects of education.

A brief diagnostic battery of neuropsychological tests was developed for a large-scale epidemiological study of dementia. We operationally defined dementia as defective memory and defective performance in at least two other areas, including orientation, abstract reasoning, construction, and language. Criterion scores for defining defective performance on each test were developed. In a pilot study that used 51 different subjects with a working diagnosis based on physicians' assessment (ie, 32 demented and 29 nondemented subjects), the test-based diagnosis agreed with the working diagnosis in all but two cases. The test battery was then applied to 430 healthy elderly subjects. Eighteen percent of those with 8 or less years of education met criteria for dementia compared with 5% of those with more than 8 years of education. We computed education-corrected scores for each test with the use of residuals from the regression of each test score on education. Based on corrected scores, 12 subjects were reclassified as nondemented and 11 as demented. Subjects who were reclassified as demented were significantly more impaired in activities of daily living than nondemented subjects who were not reclassified. Activities of daily living in subjects who were reclassified as nondemented did not differ from those in demented subjects who were not reclassified. These findings suggest that the neuropsychological battery may have utility in the diagnosis of dementia. However, neuropsychological performance may be influenced by education, and some form of adjustment, such as correction for activities of daily living, may be required in epidemiological studies.

Activities of Daily Living↗

PubMed1992

Diagnosis of dementia in a heterogeneous population. A comparison of paradigm-based diagnosis and physician's diagnosis.

Each of 430 subjects received a diagnosis using two independent methods: a test-based quantitative paradigm and a semistructured neurological examination by a physician. The paradigm diagnosis was based on a battery of tests that assessed short- and long-term verbal memory and short-term nonverbal memory, orientation, construction, abstract reasoning, and language. The subjects came from a community in Manhattan County, in New York City, and were characterized by diversity with respect to both ethnicity (29.1% black, 33.4% Hispanic) and educational level (23.5% with 6 or fewer years of education, 25.6% college educated). Based on the paradigm, 10.5% of subjects received diagnoses of dementia, 29.1% of cognitive impairment, and 60.5% of normal. Based on the physician's diagnosis, 9.8% were demented, 21.6% cognitively impaired, and 68.6% normal. There was agreement between the two diagnostic methods for 71.8% of subjects. Diagnostic disagreement (n = 121) was in most cases between normal and cognitively impaired (71.0%) or between cognitively impaired and demented (21.5%). There were only nine cases (7.5%) in which a subject was judged demented by one method and normal by the other. The reliability of each method with respect to the other was moderate (intraclass correlation coefficient, .62), while the reliability of a composite diagnosis based on both methods was much higher (.77). The paradigm was more likely than the physician to give the diagnosis of dementia to patients with low educational levels. The physician's diagnosis was strongly influenced by measures of functioning and by the mental status test administered in the semistructured neurological examination. Race and diagnosis were not related when the effect of education was controlled.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

A population-based investigation of Parkinson's disease with and without dementia. Relationship to age and gender.

Because the prevalence of idiopathic Parkinson's disease (PD) with or without dementia remains controversial, we initiated a population-based investigation in the Washington Heights-Inwood section of New York, NY, so that nearly complete case ascertainment could be achieved. A "registry" was developed for the study, and we advertised in periodicals and on radio and television. Subjects, or their records, were examined by experienced neurologists, and most underwent a battery of neuropsychological tests specifically designed for assessment in this community. All data were reviewed by a team of clinicians to achieve a consensus diagnosis. The crude prevalence of idiopathic PD, with and without dementia, was 99.4 per 100,000, increasing from 2.3 per 100,000 for those younger than 50 years to 1144.9 per 100,000 for those aged 80 years and older. The crude prevalence for PD with dementia alone was 41.1 per 100,000 and also increased with age from zero for those younger than 50 years to 787.1 per 100,000 for those aged 80 years and older. Prevalence ratios were comparable with those of other published population-based studies in similar settings. After standardization, men had PD with and without dementia more frequently than did women. The major difference between patients with and without dementia was a later estimated age at onset of motor manifestations. We conclude that PD is a frequent disorder in the elderly population that affects men and whites more frequently than women and nonwhites. Moreover, dementia in patients with PD is more frequent than previously recognized and is strongly related to the age at onset of motor manifestations.

Aged↗

PubMed1992

Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease.

Acetyl levocarnitine hydrochloride has been reported to retard dementia in patients with Alzheimer's disease. In a double-blind, parallel design, placebo-controlled pilot study of 30 mild to moderately demented patients with probable Alzheimer's disease, tests of memory, attention, language, visuospatial, and constructional abilities were administered, and the level of acetyl levocarnitine was measured in the cerebrospinal fluid. Patients were then randomly assigned to receive acetyl levocarnitine hydrochloride (2.5 g/d for 3 months followed by 3 g/d for 3 months) or placebo. After 6 months, the acetyl levocarnitine group demonstrated significantly less deterioration in timed cancellation tasks and Digit Span (forward) and a trend toward less deterioration in a timed verbal fluency task. No differences were found in any other neuropsychological test results. A subgroup with the lowest baseline scores, receiving acetyl levocarnitine, had significantly less deterioration on the verbal memory test and a significant increase in cerebrospinal fluid acetyl levocarnitine levels compared with those receiving placebo. These results suggest that acetyl levocarnitine may retard the deterioration in some cognitive areas in patients with Alzheimer's disease and stress the need for a larger study of this drug.

Acetylcarnitine↗

PubMed1992

Inverse relationship between education and parietotemporal perfusion deficit in Alzheimer's disease.

A higher prevalence of dementia in individuals with fewer years of education has suggested that education may protect against Alzheimer's disease (AD). We tested whether individuals with more years of education have a more advanced AD before it is clinically evident. As a measure of pathophysiological severity, we quantified regional cerebral blood flow (rCBF), by the 133Xenon inhalation technique; a specific pattern of flow reduction in the parietotemporal cortex corresponds to AD pathology. In 3 groups of patients with probable AD, matched for clinical measures of dementia severity but with varying levels of education, whole-cortex mean flows were comparable. However, the parietotemporal perfusion deficit was significantly greater in the group with the highest level of education, indicating that AD was more advanced in this group. We conclude that education or its covariates or both may provide a reserve that compensates for the neuropathological changes of AD and delays the onset of its clinical manifestations.

Alzheimer Disease↗

PubMed1992

Dementia after stroke: baseline frequency, risks, and clinical features in a hospitalized cohort.

We determined the frequency of dementia in a cohort of 251 patients aged greater than or equal to 60 years hospitalized with acute ischemic stroke, based on examinations performed 3 months after stroke onset. Using modified DSM-III-R criteria, we found dementia in 66 patients (26.3%). Diagnostic agreement among raters was excellent (kappa = 0.96). In a control sample of 249 stroke-free subjects recruited from the community and matched by age, we found dementia in eight subjects (3.2%). Using a logistic regression model to estimate the risk of dementia associated with stroke in the combined samples, the odds ratio (OR) for stroke patients compared with control subjects was 9.4 (p less than 0.001). Advancing age and fewer years of education were significant, independent correlates of dementia, with a trend evident for race (non-white versus white). Confining the analysis to subjects residing in the Washington Heights-Inwood community of northern Manhattan, the OR was 10.3 (p less than 0.001) with significant age and race effects. We conclude that ischemic stroke significantly increases the risk of dementia, with independent contributions by age, education, and race.

Aged↗

PubMed1992

Behavioral syndromes in Alzheimer's disease.

The Behavioral Syndromes Scale for Dementia (BSSD) is a new instrument that showed strong internal consistency and interrater reliability in an outpatient sample of 106 patients with probable Alzheimer's disease. Factor analysis provided support for a priori symptom groupings, particularly the syndromes of disinhibition and apathy-indifference. Dependency (87%), denial of illness (63%), and motor agitation (55%) were common, while sexual disinhibition (2.9%) and self-destructive behaviors (2.9%) were rare. Virtually all symptoms were predominantly minimal to mild in severity. Patients with longer illness duration were more apathetic. Disinhibited behaviors and apathy-indifference increased with greater severity of dementia. Catastrophic reactions, aggression, and agitation were associated with greater functional impairment. There was great heterogeneity in symptom presentation. In Alzheimer's disease, several behavioral changes might be direct manifestations of underlying brain pathology, rather than being solely secondary to cognitive impairment.

Activities of Daily Living↗

PubMed1992

Low dose oral haloperidol and blood levels in Alzheimer's disease: a preliminary study.

Nineteen patients with probable Alzheimer's disease who manifested psychosis or behavioral disturbance received 0.5 to 5 mg per day of oral haloperidol, with blood levels drawn on a stable daily dose. Oral dose correlated strongly with haloperidol blood levels assessed by radioimmunoassay (r = 0.82, p = .0001). The stronger correlation observed between oral dose and blood level compared with most studies in schizophrenia may be related to the fact that virtually all the Alzheimer's patients were neuroleptic naive, without the alterations in absorption and metabolism known to occur in schizophrenics receiving long-term neuroleptic treatment. Compared with oral dose, blood levels showed stronger relations to changes in symptoms and to changes in severity of extrapyramidal side effects. These preliminary data suggest that the utility of monitoring haloperidol blood levels in patients with Alzheimer's disease merits further investigation.

Aged↗