Biomedical subjects

K Marder

Publications and source records attributed to K Marder.

At least 127 records · Page 7Linked to original sources

PubMed1994

Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer's disease: prospective analyses from the Predictors Study.

OBJECTIVE: To examine whether either extrapyramidal signs or psychotic features are associated with more rapid progression of Alzheimer's disease. BACKGROUND: It has been unclear whether extrapyramidal signs and psychosis are predictors of faster course or are simply late signs. METHODS: Two hundred thirty-six patients with mild Alzheimer's disease were recruited in three cities and followed semiannually. RESULTS: Using Cox proportional hazards models that adjusted for age, sex, disease severity, and estimated duration of illness at study entry, the presence of extrapyramidal signs at entry was associated with higher relative risk (RR) of reaching moderate cognitive (RR = 2.35, 95% CI = 1.12 to 4.92) or functional (RR = 2.31, 95% CI = 1.37 to 3.90) severity, nursing home entry (RR = 2.51, 95% CI = 1.32 to 4.76), or death (RR = 3.04, 95% CI = 1.31 to 7.05). Psychosis predicted only the functional end point (RR = 1.85, 95% CI = 1.18 to 2.90). Using regression models, modified Mini-Mental State scores declined 1.30 points (95% CI = 0.16 to 2.44) per 6-month interval, more among patients with than those without extrapyramidal signs; patients with psychosis declined 1.15 (95% CI = 0.52 to 1.77) more mMMS points per interval. CONCLUSIONS: This study confirms extrapyramidal signs and psychosis as robust predictors of disease end points and rapid progression in Alzheimer's disease.

Age Factors↗

PubMed1994

Age at onset of Alzheimer's disease: relation to pattern of cognitive dysfunction and rate of decline.

We examined the pattern of cognitive impairment and rate of cognitive and functional decline as a function of age at symptom onset in 127 patients with probable Alzheimer's disease (AD). At baseline, early-onset (before age 65) and late-onset groups were mildly and comparably impaired on the modified Mini-Mental State Examination (mMMS) and the Blessed Dementia Rating Scale-Part 1 (BDRS). Repeated-measures analysis of variance revealed significantly more rapid decline in early-onset subjects over a 2-year follow-up period. Multivariate linear regression analyses indicated that age at symptom onset strongly predicted rate of decline on the mMMS and the BDRS, even after controlling for symptom duration, gender, family history of dementia, and baseline mMMS and BDRS scores. Early- and late-onset AD subjects also differed in terms of pattern of performance on the mMMS. Early-onset subjects scored significantly lower than late-onset subjects on attentional items of the mMMS at baseline and follow-up. Conversely, late-onset subjects scored significantly lower than early-onset subjects on memory and naming items at baseline, and the two groups were comparable on these tasks at follow-up. Results provide longitudinal evidence of more rapid cognitive and functional decline in subjects with early-onset AD and suggest that early-onset AD may be characterized by predominant impairment of attentional skills.

Age of Onset↗

PubMed1994

The apolipoprotein epsilon 4 allele in Parkinson's disease with and without dementia.

The epsilon 4 isoform of apolipoprotein E (Apo-E) may confer genetic susceptibility for familial and sporadic Alzheimer's disease (AD). Because dementia in AD and Parkinson's disease (PD) share many biologic and clinical features, we determined the Apo-E genotypes for 79 patients with PD, 22 of whom were demented, and for 44 age-matched healthy elderly controls from the same community. We hypothesized that if the dementia was similar to AD, there would be a higher allele frequency of apolipoprotein epsilon 4 (Apo epsilon 4) in demented PD patients compared with nondemented PD patients and controls. The epsilon 4 allele frequency for PD without dementia was 0.132, for PD with dementia, 0.068, and for controls, 0.102. There was no association between Apo epsilon 4 and dementia in the PD patients. We conclude that the biologic basis for dementia in PD may differ from that of AD.

Aged↗

PubMed1993

Relationships between extrapyramidal signs and cognitive function in a community-dwelling cohort of patients with Parkinson's disease and normal elderly individuals.

The relationship between extrapyramidal sign (EPS) severity and cognitive function was investigated in 184 patients with idiopathic Parkinson's disease (PD) and 301 normal elderly individuals from a community-dwelling cohort in northern Manhattan, New York City. Fifty-six of the patients with PD met criteria for dementia of the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised, and of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. EPS were rated according to the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological tests of memory, orientation, abstract reasoning, language, construction, and psychomotor speed. Significant associations were found between EPS and neuropsychological performance in PD patients without dementia. Yet EPS severity was unable to account for the pronounced cognitive impairment in PD dementia. Individuals in the normal group with subtle EPS, but without overt idiopathic PD, showed widespread cognitive changes, including impairment in most of the tests that differentiated PD patients from normal subjects. Prospective follow-up of these individuals will determine whether this represents a preclinical stage of PD or constitutes an early manifestation of dementia.

Aged↗

PubMed1993

Genetic susceptibility and head injury as risk factors for Alzheimer's disease among community-dwelling elderly persons and their first-degree relatives.

We performed a community-based study to investigate the relationship of genetic susceptibility and head injury to Alzheimer's disease (AD) in 138 patients with AD and 193 healthy elderly control subjects. Data concerning presence or absence of dementia and certain exposures were also obtained from 799 first-degree relatives of the patients and 1,238 first-degree relatives of the control subjects. Adjusting for age, gender, and other risk factors, the odds ratio for AD associated with head injury was 3.7 (95% confidence interval [CI], 1.4-9.7). The association was highest for head injuries that occurred after age 70. The risk of AD was higher in first-degree relatives of patients with onset prior to age 70 than in relatives of control subjects (risk ratio [RR] = 2.5; 95% CI, 1.1-5.6). The risk was not increased for relatives of patients with onset of AD at age 70 or older. Compared with relatives without head injury, the risk of AD was increased among both head-injured relatives of patients (RR = 5.9; 95% CI, 2.3-14.8) and head-injured relatives of control subjects (RR = 6.9; 95% CI, 2.5-18.9). Our results are consistent with the hypothesis that severe head injury and genetic susceptibility are associated with AD. Both associations concur with current concepts regarding the role of amyloid in AD. Although we regard head injury, like genetic susceptibility, to be a putative risk factor for AD, the temporal relationship between head injury and AD warrants further investigation.

Age Factors↗

PubMed1993

Multicenter study of predictors of disease course in Alzheimer disease (the "predictors study"). I. Study design, cohort description, and intersite comparisons.

Clinicians should be able to provide the patient with Alzheimer disease (AD) and the family with an accurate prediction of what to expect, but the variability in the rate of disease progression precludes this. In several previous studies, specific clinical signs such as muscular rigidity, myoclonus, and hallucinations or delusions were associated with rapid progression to a more severe stage of dementia or death. The "Predictors Study," a longitudinal study at three independent sites, was designed to develop a predictor model of the natural history of Alzheimer disease. The study was conducted at three study sites, New York, Baltimore, and Boston in a cohort of 224 patients with early probable AD. This article describes the design and implementation of the Predictors Study, and compares features of the study cohort at baseline across sites. Patients were all at the mild stage of disease at entry and were relatively comparable across sites. Extrapyramidal signs and delusions were common, but myoclonus was rarely observed.

Activities of Daily Living↗

PubMed1993

Multicenter study of predictors of disease course in Alzheimer disease (the "predictors study"). II. Neurological, psychiatric, and demographic influences on baseline measures of disease severity.

The "Predictors Study" is a prospective cohort study of the natural history of Alzheimer disease (AD), the aim of which is to identify milestones in disease progression and to develop a model to predict disease course in individual patients. The empirical background to this study is based on previous reports that the presence of extrapyramidal signs (EPS), myoclonus, and psychosis in AD may signify greater disease severity at any given stage and a more rapid course of the disease over time. The present analyses were conducted to determine whether these independent "predictor" variables were associated with greater disease severity at baseline within a new cohort of 224 mild AD patients recruited from three different medical centers (in New York, Baltimore, and Boston). Measures of disease severity were provided by the modified Mini-Mental State Examination (mMMSE) and the Blessed Dementia Rating Scale (BDRS), which measures functional capacity. Independent variables were EPS, delusions, and slowing of the posterior dominant EEG rhythm. The frequency of myoclonus and hallucinations was too low to permit adequate statistical assessment of their effects at this time. EPS and EEG slowing were associated with low mMMSE scores, whereas delusions were primarily associated with impaired functional capacity. These effects were independent of the influence of age and disease duration. These results indicate that the effects of these independent variables can be detected at mild stages of AD and that these effects can be generalized across different geographical regions.

Aged↗

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

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

Biopsy-proven isolated sarcoid meningitis. Case report.

Neurosarcoidosis without systemic involvement is rare and difficult to diagnose. The case of a 27-year-old man with a 6-week history of headache, mental status changes, and polyradiculopathy attributable to hypoglycorrheic lymphocytic meningitis is presented. Extensive testing for occult systemic sarcoidosis was negative. The presence of noncaseating granulomatous inflammation was established by open brain biopsy, and the patient improved clinically with oral steroid therapy. In individuals with undiagnosed chronic meningitis, brain biopsy may be necessary to rule out isolated neurosarcoidosis.

Adult↗

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

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

Neurologic and neuropsychological manifestations of human immunodeficiency virus infection in intravenous drug users without acquired immunodeficiency syndrome. Relationship to head injury.

We examined 99 human immunodeficiency virus (HIV)-negative and 122 HIV-positive intravenous drug users (IVDUs) without acquired immunodeficiency syndrome (AIDS) to determine whether HIV-positive IVDUs had more neurologic and neuropsychological impairment than their HIV-negative counterparts. Controlling for age, education, drug use, history of head injury, and interactions between head injury and HIV status and drug use, HIV-positive subjects had more extrapyramidal signs and frontal release signs. These findings persisted when asymptomatic HIV-positive subjects without systemic signs of infection and HIV-negative subjects were compared. Neurologic findings were more severe in those with more systemic illness. Among those reporting a history of head injury with loss of consciousness, neuropsychological performance was significantly worse in the HIV-positive subjects, and this increased with severity of illness. This was not true in the group without head injury, suggesting an interaction between history of head injury and the seropositive state. No relationship was noted between head injury and either drug use or HIV state. Therefore, subtle neurologic and neuropsychological abnormalities may precede clinical evidence of AIDS in IVDUs and may be more evident in those with head injury.

Adult↗