Search PubMed⌕ Search

Biomedical subjects

R Mayeux

Publications and source records attributed to R Mayeux.

At least 163 records · Page 9Linked to original sources

Risk of dementia in first-degree relatives of patients with Alzheimer's disease and related disorders.

First-degree relatives of patients with Alzheimer's disease (AD) are at greater risk for dementia when compared with the relatives of their healthy peers, but not when compared with the relatives of patients with Parkinson's disease. This may indicate that the risk of dementia in these relatives is not specific to AD or that these studies are biased. We obtained a family history and vital status information on each first-degree relative of patients attending a clinic and in a group of recruited healthy elderly subjects. Patients formed two groups: probable AD and other forms of dementia or cognitive disorders without dementia. The odds of dementia in first-degree relatives did not differ between patient groups. The odds of dementia in relatives of patients with probable AD or other forms of dementia was six times that in the relatives of the healthy elderly subjects. The cumulative incidence of dementia increased with age in the first-degree relatives of all subjects. Approximately 50% of the first-degree relatives of patients with AD were demented by age 91 years, but almost the same number of the other patient group's relatives were demented as well. That figure was never reached in the healthy elderly subject's relatives. Because the risk of dementia in first-degree relatives of patients with AD was similar to that for patients with other disorders, we cannot exclude the possibility that this is the result of selection and information biases. Our investigation implies that the increased risk of dementia may not be specific to relatives of patients with AD; the risk may also be increased in first-degree relatives of patients with other neurologic disorders.

Aged↗

Tritiated imipramine binding. A peripheral marker for serotonin in Parkinson's disease.

Tritiated imipramine binding in platelets has been used to evaluate serotonin activity in depression in previous studies. This article examined this marker as a possible measure of central nervous system serotonergic activity for depression in patients with Parkinson's disease (PD). The number of binding sites was significantly lower in depressed patients with PD than in a healthy control group. Patients with PD who were not depressed had lower values than the comparison group, but this difference was not significant. We also found a significant correlation between the receptor site values in platelets and cerebrospinal fluid levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (r = .59), but this was independent of a diagnosis of depression. Receptor site values were examined to identify appropriate cutoff scores to predict depression in the group of patients with PD. A maximum sensitivity of 50% was achieved with a specificity of 64%. Our results strongly support a generalized alteration in serotonin metabolism in depressed patients with PD, but tritiated imipramine binding in platelets is not a useful diagnostic tool for depression.

Aged↗

Cumulative risks of developing extrapyramidal signs, psychosis, or myoclonus in the course of Alzheimer's disease.

Cumulative risks of developing extrapyramidal signs, psychosis, and myoclonus in the course of Alzheimer's disease (AD) were estimated in 72 patients with probable AD by the Kaplan-Meier survival method. The cumulative risk functions were found to increase at different rates for different signs as AD progressed. Comparisons of the cumulative risk functions revealed that in the early stages of AD, extrapyramidal signs and psychosis were more likely to develop than myoclonus. As AD progressed, the risk of developing myoclonus became as great as that of developing the other two signs. This study suggests that extrapyramidal signs, psychosis, and myoclonus represent developmental features that mark the progression of AD, rather than indicators of disease subtypes. The estimated cumulative risk functions set a reasonable expectation for the timing and likelihood of the emergence of the clinical signs. This, in turn, might aid in disease prognosis because the biological bases of these signs have been established and they have been shown to be predictive of other markers of disease course.

Aged↗

Interrater reliability of extrapyramidal signs in a group assessed for dementia.

Extrapyramidal signs were rated by three neurologists in 20 patients who had either been diagnosed as having probable Alzheimer's disease or who were being evaluated for dementia. In general, good interrater reliability was found for the presence or absence of extrapyramidal signs, although agreement over the presence of some signs was reduced when distinctions between normality and slight departures from normality were required.

Aged↗

Multidisciplinary baseline assessment of homosexual men with and without human immunodeficiency virus infection. I. Overview of study design.

Although much is known about the virus believed by most experts to be the cause of the acquired immunodeficiency syndrome and about its pathogenic actions, major areas of ignorance remain. Among these are the reasons for the varying time between infection with human immunodeficiency virus and development of acquired immunodeficiency syndrome, the relationship between neurologic and medical aspects of the disease, the time course of neuropsychological findings, and the prevalence of psychiatric morbidity. We assessed 124 homosexual men who were positive for human immunodeficiency virus and 84 who were negative for the virus. In this article we describe the study design, method of recruitment, and medical and demographic characteristics of the cohort, which will be followed up for 5 years.

Adolescent↗

Glucocorticoid level and neuropsychiatric symptoms in homosexual men with HIV infection.

OBJECTIVE: There is a controversial literature suggesting that stress, anxiety, and depression are harmful to the immune system and therefore to health. Preclinical studies indicate that activation of the hypothalamic-pituitary-adrenal (HPA) axis by stress may be responsible for immunocompromise. The goal of this study was to assess this phenomenon in human immunodeficiency virus (HIV) infection. METHOD: Homosexual men in the community who did not meet modified Centers for Disease Control criteria for acquired immune deficiency syndrome (AIDS) were recruited for the study; 113 of the men were HIV positive and 77 were HIV negative. Very few of the men studied suffered from depression or anxiety disorder at the time of the first assessment. Twenty-four-hour urinary free cortisol levels were obtained from the 112 HIV-positive and 75 HIV-negative men whose 24-hour urine volumes were 500 ml or more. Cortisol levels were correlated with measures of medical, immunological, neurological, and psychiatric status. RESULTS: Small but significant correlations between 24-hour urinary free cortisol and medical status, level of depression, and level of anxiety were found in the HIV-positive group. There was no relationship between cortisol level and the number of CD4+ or CD8+ T lymphocytes or the CD4-CD8 ratio. CONCLUSIONS: Although HPA activation may be associated with stress in cases of HIV infection, it does not seem to be associated with further loss of CD4+ T lymphocytes. Subjects with HIV infection with the most evidence of medical complications may also be the most anxious and depressed.

Adult↗

Are demented patients with Parkinson's disease accurately reflected in prevalence surveys? A survival analysis.

We re-reviewed 257 patient records previously reviewed for an incidence study of dementia in Parkinson's disease (PD) to determine the frequency, date of death, and cause of death. We posited that if disease duration is shortened when dementia occurs, then dementia may be far more common than reflected in prevalence studies. There were 17 deaths among 65 demented patients and 28 deaths among 168 nondemented patients. When we matched a subset of the nondemented patients to the demented patients by age and disease duration distributions, the demented subjects had significantly more deaths (p less than 0.02), and survival among demented subjects was decreased (p less than 0.05). Dementia was a significant predictor of death in this sample. We conclude that dementia reduces survival in patients with PD. Incidence is a much better measure of dementia in PD than prevalence because shortened duration makes it less likely to detect dementia in prevalence surveys.

Aged↗

Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder.

Alzheimer's disease, a fatal neurodegenerative disorder of unknown aetiology, is usually considered to be a single disorder because of the general uniformity of the disease phenotype. Two recent genetic linkage studies revealed co-segregation of familial Alzheimer disease with the D21S1/S11 and D21S16 loci on chromosome 21. But two other studies, one of predominantly multiplex kindreds with a late age-of-onset, the other of a cadre of kindreds with a unique Volga German ethnic origin, found absence of linkage at least to D21S1/S11. So far it has not been possible to discern whether these conflicting reports reflect aetiological heterogeneity, differences in methods of pedigree selection, effects of confounding variables in the analysis (for example, diagnostic errors, assortative matings), or true non-replication. To resolve this issue, we have now examined the inheritance of five polymorphic DNA markers from the proximal long arm of chromosome 21 in a large unselected series of pedigrees with familial Alzheimer's disease. Our data suggest that Alzheimer's disease is not a single entity, but rather results from genetic defects on chromosome 21 and from other genetic or nongenetic factors.

Alzheimer Disease↗

A pilot study of risk factors for dementia in Parkinson's disease.

To determine whether the risk factors for dementia in idiopathic Parkinson's disease (IPD) are similar to the risk factors for Alzheimer's disease, we conducted a case-control study of potential risk factors. A structured interview was administered to surrogates of 17 demented subjects with IPD and 54 nondemented subjects. Two factors emerged as possible risks for dementia. Demented patients were older than nondemented patients, although the duration of symptoms was similar. A family history of dementia was present in 30% of the demented group and 5.6% of the nondemented group. Dementia was most often reported among siblings. No difference was seen in toxic and occupational exposure, personal habits, or medical or surgical illnesses. We conclude that dementia in IPD shares some common risk factors with Alzheimer's disease. Efforts to assess the contribution of genetic susceptibility or shared environmental influences may clarify the relationship between these two diseases.

Aged↗

A controlled trial of piracetam in intellectually impaired patients with Parkinson's disease.

Twenty patients with Parkinson's disease and marked intellectual impairment or dementia participated in a double-blind placebo controlled trial of the nootropic, piracetam. A standardized neurological examination, a neuropsychological test battery, and a functional scale, The Sickness Impact Profile, were completed for all patients. They were then assigned by blind randomization to drug or placebo conditions receiving 3.2 g of piracetam or an identical amount of placebo for 12 weeks. The dose was increased to 4.8 g for an additional 12 weeks. Neurological, psychological, and functional measures were rated as improved, unchanged, or worsened in comparison to baseline performance. Twenty-five percent of the patients did not complete the trial for reasons unrelated to the medication. Although there was a significant improvement on one subtest of the functional scale, no significant effects were demonstrated in cognitive or neurological measures.

Aged↗

Measurement and prediction of functional capacity in Alzheimer's disease.

Functional loss in Alzheimer's disease is difficult to measure or predict. The Blessed Dementia Rating Scale (Part 1) correlates well with postmortem changes but is not an effective antemortem index of functional change since disparate behavioral domains are assessed. We performed a factor analysis of the Blessed items in 187 patients with clinically diagnosed Alzheimer's disease and identified 4 independent factors: (I) cognitive, (II) personality, (III) apathy, and (IV) basic self-care. An endpoint, consisting of a score indicative of moderate disability, was determined for each factor. We then used life table analyses to compare the probability of reaching these endpoints over time in longitudinally followed patients. Patients with extrapyramidal signs at their initial visit reached the factor IV endpoint sooner, and those with psychosis or no family history of dementia also reached the factor I endpoint faster. These data illustrate the utility of a multifactorial approach to the assessment of functional capacity in Alzheimer's disease, and also indicate that extrapyramidal symptoms and psychosis are powerful predictors of the rate of decline in basic self-care activities and cognition.

Aged↗

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

The proportion of patients with idiopathic Parkinson's disease (PD) who are considered demented ranges from 10% to 15%. Because dementia may affect survival in PD, the incidence rate of dementia, rather than proportion, would be a more accurate measure of disease frequency. We previously estimated the proportion of patients with PD and dementia to be 10.9% from the records of a cohort with the idiopathic form of PD in a major medical center. We reviewed the clinical records of this cohort after 4 years and 9 months to estimate the incidence rate of dementia. We identified 65 new cases of dementia from the 249 patient-records available. Using the number of person-years of follow-up for each case as the denominator, we estimated the overall incidence rate to be 69 per 1,000 person-years of observation. The mean age of this cohort was 71.4 years. The cumulative incidence of dementia increased with age. By 85 years of age, over 65% of the surviving members of the cohort were demented. The age-specific incidence rates for dementia in this cohort of PD were significantly greater than for a similarly aged cohort of healthy elderly people. The age-specific standard morbidity ratios indicated that, compared with people of similar ages, patients with PD have the highest increase in risk for dementia between ages 65 and 75.

Age Factors↗

Soluble derivatives of the beta amyloid protein precursor in cerebrospinal fluid: alterations in normal aging and in Alzheimer's disease.

We isolated and sequenced a soluble approximately 25 kDa amino-terminal derivative of the beta amyloid protein precursor (beta APP) that is readily detected in human cerebrospinal fluid (CSF). In CSF samples from 24 Alzheimer's disease (AD) patients and 12 controls, we then quantitated this approximately 25 kDa form as well as the approximately 125 and approximately 105 kDa derivatives that we previously identified. Our analysis shows (1) that, in AD, there is a significant decrease in the relative amount of the approximately 105 kDa form and a corresponding significant increase in the relative amount of the approximately 25 kDa form; (2) that these changes correlate with the mental status of the AD patients; and (3) that the same changes occur to a lesser extent in elderly as compared with young control patients. These observations indicate that processing of the beta APP changes in normal individuals as they age and to a greater extent in those who develop AD. The changes in beta APP derivatives that we have observed in CSF could have major implications because they may reflect fundamental mechanisms responsible for amyloid deposition and can be measured in living patients.

Adult↗

Depression in the patient with Parkinson's disease.

Depression is the most commonly encountered mental change in patients with Parkinson's disease. However, its cause is controversial and little is known about its natural history. Some view depression as reactive to the physical disability inherent to Parkinson's disease; however, others view the depressive disorder as the direct result of underlying biochemical changes caused by the disease process. Abnormalities within the serotonin metabolic pathway have been observed in depressed patients with Parkinson's disease and may help to explain why this form of depressive disorder is so common and persistent. Other forms of depression share this biochemical alteration. Attempts to alleviate depression with serotonin agonists have proven successful. Current research efforts are exploring biological aspects of depression in Parkinson's disease and the epidemiology of this disorder as a model of depression in the elderly, medically ill patient.

Age Factors↗