Biomedical subjects

K Marder

Publications and source records attributed to K Marder.

At least 91 records · Page 5Linked to original sources

PubMed1997

Alzheimer's disease after remote head injury: an incidence study.

OBJECTIVE: To evaluate a history of remote head injury as a risk factor for subsequent dementia due to Alzheimer's disease. METHODS: 271 participants of a community based longitudinal study of aging in north Manhattan without evidence of significant cognitive impairment were interrogated for a history of head injury on two occasions at entry into the study. The examining physician sought a history of head injury with loss of conciousness. Independently, a risk factor interviewer inquired about a history of head injury with loss of consiousness or amnesia, the duration of any loss of consiousness, and the date of the head injury. Patients were followed up with standardised annual evaluations for up to five years to determine the first occurrence of dementia. RESULTS: Over the course of the study incident dementia due to probable or possible Alzheimer's disease was diagnosed in 39 patients. Cox proportional hazards modelling showed that a history of head injury with loss of consiousness reported to the physician was associated with earlier onset of dementia due to Alzheimer's disease (relative risk (RR) = 4.1, 95% confidence interval (95% CI) 1.3-12.7). head injury with loss of consiousness or amnesia reported to the risk factor interviewer was not significantly associated with earlier onset of Alzheimer's disease overall (RR 2.0, 95% CI 0.7-6.2), but those who reported loss of consiousness exceeding five minutes were at significantly increased risk (RR 11.2, 95% CI 2.3-59.8). Incident Alzheimer's disease was significantly associated with head injury which occurred within the preceding 30 years (RR 5.4, 95% CI 1.5-19.5). CONCLUSION: The results of this cohort study are consistent with the findings of several case-control studies suggesting that head injury may be a risk factor for Alzheimer's disease.

Age of Onset↗

PubMed1997

Association of subjective memory complaints with subsequent cognitive decline in community-dwelling elderly individuals with baseline cognitive impairment.

OBJECTIVE: The validity of subjective memory complaints has been questioned by clinical studies that have shown little relationship between memory complaints and objective memory performance. These studies often have been cross-sectional in design, have excluded individuals with cognitive impairment, or have lacked a comparison group. The authors conducted a study that attempted to avoid these limitations. METHOD: Memory complaints of 364 nondemented, community-dwelling elderly individuals were recorded as present or absent at the baseline evaluation. After 1 year, 169 subjects were reevaluated. Standardized neurologic and neuropsychological evaluations were used at each assessment to classify subjects as normal or cognitively impaired. RESULTS: At baseline, 31% of the normal subjects and 47% of those with cognitive impairment had memory complaints. Subjects with memory complaints had higher Hamilton depression scale scores than subjects without memory complaints but equivalent scores on a measure of total recall. At follow-up, multivariate analyses showed that subjects with baseline memory complaints had significantly greater decline in memory and cognition than subjects without memory complaints. Secondary analyses showed this effect to be confined to subjects with baseline cognitive impairment. CONCLUSIONS: Memory complaints may lack validity in subjects with normal cognition, but in nondemented individuals with cognitive impairment, memory complaints may predict subsequent cognitive decline.

Aged↗

PubMed1997

Participation in clinical trials and long-term outcomes in Alzheimer's disease.

The objective of this study was to determine whether participation in clinical trials affects long-term outcomes in Alzheimer's disease (AD). Participation in clinical trials for persons with dementia is often justified on the grounds that patients benefit from the medical oversight typical of trials, even when experimental agents do not demonstrate short-term benefits. This claim has not been rigorously assessed. Of 215 community-resident subjects enrolled in a prospective study of outcomes in AD, 101 participated in randomized clinical trials (RCTs) during the first 2 years of follow-up. These subjects were compared with subjects who met eligibility requirements for RCTs but did not participate (N = 57) and with subjects who were ineligible (N = 57), over a total of 3.5 years of follow-up. Survival analyses assessed risk of death, nursing home placement, and incident functional deficit end points, adjusting for baseline differences. Subjects who participated in RCTs were younger and more highly educated. Mortality, risk of hospitalization, number of medical examinations conducted by study physicians, and onset of severe functional deficit did not differ between the groups, but risk of nursing home admission was significantly lower among RCT participants compared with eligible nonparticipants and ineligible subjects (16.8% versus 36.8% and 31.6%, respectively [p = 0.01]). The difference in risk of nursing home placement may represent a long-term, drug-related benefit to patients, a selection effect (caregivers of patients who participate in RCTs differ from caregivers of patients who do not), or a positive effect on caregivers (greater contact with a medical service may be associated with better care-giving outcomes). Further research is required to assess these effects.

Aged↗

PubMed1997

Altered systemic iron metabolism in Parkinson's disease.

Iron deposition in the substantia nigra in Parkinson's disease has been associated with an increase in lactoferrin receptors and a reduction in ferritin concentration. This accumulation of iron in the brain may accelerate free radical formation, lipid peroxidation, and neuronal death. Remarkably, there are few data available concerning systemic iron metabolism in Parkinson's disease. We measured total iron binding capacity and circulating iron, ferritin, transferrin, and transferrin receptors; calculated transferrin saturation; and estimated dietary iron intake in patients with idiopathic Parkinson's disease and in controls. Concentrations of circulating iron, ferritin, and transferrin as well as total iron binding capacity and transferrin saturation were significantly lower in patients than controls. There were no differences in transferrin receptors or dietary intake of iron. The decrease in levels of systemic ferritin and transferrin and the total iron binding capacity parallels observations in a Parkinson's disease brain, but the reductions in serum iron concentrations and transferrin saturation do not, and were unexpected. These results suggest the existence of a defect in the systems that regulate the synthesis of the major proteins of iron metabolism in the liver as well as the brain in Parkinson's disease that may, over time, expedite entry of iron into the brain and decrease iron in the extracellular compartment.

Aged↗

PubMed1996

Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease.

BACKGROUND: Oestrogen use by postmenopausal women has many health benefits, but findings on the effect of oestrogen in Alzheimer's disease are conflicting. Oestrogen promotes the growth and survival of cholinergic neurons and could decrease cerebral amyloid deposition, both of which may delay the onset or prevent Alzheimer's disease. To investigate whether use of oestrogen during the postmenopausal period affects the risk of Alzheimer's disease, we studied 1124 elderly women who were initially free of Alzheimer's disease, Parkinson's disease, and stroke, and who were taking part in a longitudinal study of ageing and health in a New York City community. METHODS: Relative risks and age-at-onset distributions were calculated from simple and adjusted Cox proportional hazards models. Standard annual clinical assessments and criterion-based diagnoses were used in follow-up (range 1-5 years). FINDINGS: Overall, 156 (12.5%) women reported taking oestrogen after onset of menopause. The age at onset of Alzheimer's disease was significantly later in women who had taken oestrogen than in those who did not and the relative risk of the disease was significantly reduced (9/156 [5.8%] oestrogen users vs 158/968 [16.3%] nonusers; 0.40 [95% Cl 0.22-0.85], p < 0.01), even after adjustment for differences in education, ethnic origin, and apolipoprotein-E genotype. Women who had used oestrogen for longer than 1 year had a greater reduction in risk; none of 23 women who were taking oestrogen at study enrolment has developed Alzheimer's disease. INTERPRETATION: Oestrogen use in postmenopausal women may delay the onset and decrease the risk of Alzheimer's disease. Prospective studies are needed to establish the dose and duration of oestrogen required to provide this benefit and to assess its safety in elderly postmenopausal women.

Age of Onset↗

PubMed1996

Modeling the influence of extrapyramidal signs on the progression of Alzheimer disease.

OBJECTIVE: To determine how the advent of extrapyramidal signs influences the progression of Alzheimer disease as measured by standard clinical measures. DESIGN: We applied growth curve models to prospective data to characterize patients' cognitive and functional changes over time. To detect changes in disease course related to extrapyramidal signs, their onset was treated as a time-dependent covariate. SETTING: Three research medical centers. PARTICIPANTS: Patients (n = 217) with probable Alzheimer disease. INTERVENTION: Patients were followed up semiannually for 5 years. MAIN OUTCOME MEASURES: Scores on the modified Mini-Mental State Examination and measures of basic and instrumental activities of daily living from the Blessed Dementia Rating Scale. RESULTS: For basic and instrumental activities of daily living, disease course was more rapid once extrapyramidal signs developed. Decline in the modified Mini-Mental State Examination score was greater at the time the signs developed, but not at subsequent visits. CONCLUSIONS: The point at which extrapyramidal signs emerge is associated with measurable acceleration in the progression of Alzheimer disease. This may in part explain why extrapyramidal signs are associated with a poorer prognosis. The differential influence of extrapyramidal signs on cognitive and functional measures suggests that the pathological changes underlying these disease features may vary.

Aged↗

PubMed1996

Dietary lipids and antioxidants in Parkinson's disease: a population-based, case-control study.

Oxidative stress plays an important role in the pathogenesis of Parkinson's disease (PD). In a population-based, case-control study we examined whether dietary intake of antioxidants and other oxidative compounds was associated with PD. Dietary intake was assessed by a semiquantitative food-frequency questionnaire in 110 PD case patients and 287 control subjects. A higher caloric intake was observed in patients with PD and did not vary with increasing duration of symptoms. Energy-adjusted fat intake was significantly higher among patients with PD than control subjects (p for trend = 0.007). Intake of protein (p for trend = 0.17) and carbohydrates (p for trend = 0.46) did not differ in patients and control subjects. Analyses of the primary sources of fat indicated that increasing intake of animal fats were strongly related to PD (odds ratio, 5.3; 95% confidence interval, 1.8-15.5; p for trend = 0.001). No significant differences were observed for intake of vitamins with antioxidant activity. An increase in the consumption of animal fats among patients with PD is consistent with the hypothesis that oxidative stress and lipid peroxidation are important in the pathogenesis of this disease. No effect of vitamins with antioxidant activity, either from food or supplements, was observed.

Aged↗

PubMed1996

Prevalence of a history of shaking in persons 65 years of age and older: diagnostic and functional correlates.

The purpose of this study was to determine the prevalence and functional and diagnostic correlates of reported shaking in the community-dwelling elderly. We conducted a standardized neurological evaluation of 1,056 nondemented Medicare recipients in Washington Heights-Inwood, Northern Manhattan (New York). Of 1,056 patients, 108 reported shaking (10.2%). The prevalence of reported shaking did not increase with age. It did differ between ethnic groups, but when adjusted for depression and score on the Schwab and England Activities of Daily Living (ADL) scale, this difference was insignificant. The age-adjusted prevalence was similar for women and men. Neurological examination of the 108 who reported shaking showed that 8.3% had tremor at rest, 17.6% had tremor with action, 5.6% had dyskinesia or chorea, and an additional 28.7% had various problems in coordination or movement. The remaining 39.8% had neither tremor nor problems in coordination or movement. Only 2.9% of individuals with reported shaking had Parkinson's disease (PD), 8.7% had essential tremor, and 2.1% had oral-buccal-lingual dyskinesia. Of the remaining 86.3%, 29 (31%) had no identifiable medical condition. Those who reported shaking were less independent with ADLs, regardless of presence of tremor on examination. Shaking is commonly reported by the community-dwelling elderly. It does not necessarily identify individuals with essential tremor and PD, and is related to decreased independence in ADLs.

Activities of Daily Living↗

PubMed1996

Reliability of patient completion of the historical section of the Unified Parkinson's Disease Rating Scale.

Evaluating the reliability of self-assessed disability in patients with Parkinson's disease (PD) is important for therapeutic trials epidemiologic surveys. This is the first study to examine the interrater reliability between physician and patient in the historical section of the Unified Parkinson's Disease Rating Scale (UPDRS). Thirty consecutive subjects with idiopathic PD self-administered the historical section of a modified UPDRS. This instrument was then readministered to these 30 subjects by a neurologist. Interobserver reliability was assessed with the weighted kappa statistic (kw). The kw for each of the 17 items in the historical section of the UPDRS ranged from 0.63 to 1.0 (moderate to excellent agreement). Total kw = 0.83 (95% confidence interval = 0.79-0.87). There were no correlations between kw and age, disease duration, dose of levodopa, Hoehn and Yahr score, Schwab and England score, or modified Mini-Mental State score. Nondemented subjects with PD may reliably assess their level of disability by self-administering the historical section of the UPDRS. This has important implications for the reliable use of self-administered disability instruments for clinical research.

Activities of Daily Living↗

PubMed1996

Application of a growth curve approach to modeling the progression of Alzheimer's disease.

BACKGROUND: Studies using clinical measures to track AD progression often assume linear declines over the entire course of the disease, which may not be justified. The objective of this study was to model change in measures of the clinical severity of Alzheimer's disease (AD) over time. METHODS: We developed a method to apply growth curve models to prospective data and characterize AD patients' functional change over time. Data from the modified Mini-Mental State Examination (mMMSE) and measures of basic and instrumental ADL, administered semiannually for up to 5 years to 236 patients with probable AD, were modeled. RESULTS: The rate of decline in mMMS scores per 6-month interval gradually increased as scores dropped from the maximum of 57 to 20. The rate of decline then decreased as scores approached 0, resulting in an inverse "S" curve. The rate of increase in instrumental ADL scores per interval attenuated as the scores increased, while that for basic ADL scores across intervals was constant. CONCLUSIONS: Differences in the pattern of progression of the three measures is in part a function of their psychometric properties. The progression curves may also reflect content-specific features of the instruments. Superimposition of the modeled decline in these three content areas suggests a hypothetical model of the relative timing of cognitive and functional changes in AD.

Activities of Daily Living↗

PubMed1996

Quality of life in patients with Alzheimer's disease as reported by patient proxies.

OBJECTIVE: To measure behaviors indicative of quality of life (QOL) in patients with Alzheimer's disease and to examine correlates of patient QOL. DESIGN: Cross-sectional investigation. SETTING: Multi-center study. PARTICIPANTS: Sample of 130 diagnosed patients. PRINCIPAL OUTCOME MEASURES: Proxy ratings of (1) the frequency, opportunity, and enjoyment of 15 non-ADL activities potentially within the capacity of a demented person, and (2) the frequency of a series of positive and negative affects, evident in clearly demarcated facial and bodily expressions. RESULTS: QOL ratings were reliably elicited. Family and institutional caregivers differed only in reports of opportunity for patient activity. Frequency of activities declined with increasing severity of dementia. The frequency of negative affects increased and positive affects declined with increasing severity of dementia, but correlations were weak. High QOL, defined by frequent activity and positive affect, was evident in a quarter of the sample. In multivariate models, functional and cognitive status independently predicted QOL among community-resident older adults; only absence of antipsychotics was related to QOL among older people in nursing homes. Patient education, a marker of premorbid state, independently predicted some activity patterns. CONCLUSIONS: Although the subjective world of the demented patient is not directly accessible, readily observable behaviors offer a basis for assessing QOL.

Affect↗

PubMed1996

Neurologic consequences of HTLV-II infection in injection-drug users.

Several case reports have suggested an association between human T-cell lymphotropic virus type II (HTLV-II) infection and chronic neurologic disease. We performed serial neurologic examinations in injection-drug users (IDU), a group known to be at increased risk for HTLV-II infection. At baseline, those infected with HTLV-II alone, human immunodeficiency virus (HIV) alone, or both were significantly more likely to have neurologic disability than uninfected subjects. Longitudinally, HTLV-II infection was independently associated with the development of global neurologic disability and neuropathy, suggesting that HTLV-II causes neurologic disease.

AIDS Dementia Complex↗

PubMed1996

The Clinical Dementia Rating scale: community-based validation of "profound' and "terminal' stages.

The original version of the Clinical Dementia Rating (CDR) scale correlates with other dementia rating scales, and predicts nursing home (NH) admission and death. To validate the extended components of the scale, we analyzed data from subjects participating in a community-based study of dementia. The extended CDR scale also correlated with measures of dementia severity and NH residence. "Profound" and "terminal" stages predicted shortened survival. The extended CDR scale should be useful in studies of the later stages of dementia.

Activities of Daily Living↗

PubMed1996

Risk of Parkinson's disease among first-degree relatives: A community-based study.

OBJECTIVE: To determine the relative risk (RR) and cumulative incidence of idiopathic Parkinson's disease (PD) in first-degree relatives of PD patients compared with relatives of controls from the same geographic region. DESIGN: A family history questionnaire was used to obtain information on all first-degree relatives of cases and controls. A subset of these first-degree relative was also examined. A Cox proportional hazards model with double-censoring techniques for missing information was used to model the RR for PD, adjusting for gender, ethnicity, and relationship to proband. RESULTS: A total of 1,458 first-degree relatives of 233 PD patients were 2.3 times as likely (95% CI = 1.3 to 4.0) as 7,834 relatives of 1,172 controls to develop PD. The cumulative incidence of PD to age 75 among first-degree relatives of PD patients was 2% compared with 1% among first-degree relatives of controls. The risk in male first-degree relatives was higher than in female relatives (RR = 2.0, 95% CI = 1.1 to 3.4) and the risk in relatives of Caucasians was higher than in African-Americans and Hispanics (RR = 2.4, 95% CI = 1.4 to 4.1). Risk for siblings and parents of probands was similar. CONCLUSIONS: Susceptibility to PD is increased in first-degree relatives of both sporadic and familial cases. The pattern of inheritance and the relationship between genetic and environmental risk factors warrant further study.

Aged↗

PubMed1996

A preliminary study of apolipoprotein E genotype and psychiatric manifestations of Alzheimer's disease.

We evaluated the frequency of depression and psychosis in 46 patients with AD and 135 control subjects with the apolipoprotein (APO) E3/3 or E3/4 genotype. Patients with AD and the APOE3/4 genotype had a more than threefold increase in the signs of depression and psychosis when compared with either patients with the APOE3/3 genotype or to control subjects. Our preliminary study suggests that the phenotype of AD associated with the epsilon 4 allele is more likely to include psychiatric manifestations.

Aged↗

PubMed1996

Gender Differences in HIV-Related Neurological Progression in a Cohort of Injecting Drug Users Followed for 3.5 Years.

We evaluated potential gender differences in the development of HIV related neurologic impairment, by matching 38 pairs of HIV positive male and female injecting drug users on their baseline age, education, disease stage and CD4 counts, and following them for 3.5 years. Adjusting for age, education, drug use, history of head injury and baseline CD4 count, more women had sensory abnormalities and symptoms than men at baseline, but the odds of having neurological impairment, particularly extrapyramidal signs and sensory abnormalities were increased over time in men but not in women. Men with ARC or AIDS had more neurological impairment than women in similar stages of illness. This study suggests further investigations of gender differences in HIV disease progression.

CD4 Lymphocyte Count↗

PubMed1995

Linear rank tests for doubly censored data.

This paper establishes the asymptotic properties of the non-parametric maximum likelihood estimator of the survival function based on data censored both from the left and the right. We show that the sample mean based on the survival estimator converges to a normal distribution, and we derive non-parametric tests for the differences in survival functions. The methods are applied to a study of dementia associated with Parkinson's disease.

Adult↗

PubMed1995

The frequency of idiopathic Parkinson's disease by age, ethnic group, and sex in northern Manhattan, 1988-1993.

Sex and ethnic differences in the frequency of Parkinson's disease have become increasingly important, because putative genetic and environmental risk factors have been identified. The authors estimated the prevalence and incidence of Parkinson's disease in a culturally diverse community in New York City over a 4-year period (January 1, 1988-December 31, 1991) using a disease registry substantiated, for older individuals, by a subsequent survey of a random sample of Medicare recipients between January 1, 1992, and December 31, 1993. The prevalence rate was 107 per 100,000 persons, and over a 3-year period the average incidence rate was 13 per 100,000 person-years. Age-adjusted prevalence rates were lower for women than for men in each ethnic group and were lower for blacks than for whites and Hispanics. Incidence rates were highest among black men, but they were otherwise comparable across the sex and ethnic groups. The estimated cumulative incidence of Parkinson's disease up to age 90 years was lower for women than for men, which could partially explain the lower prevalence rate. By ethnic group, the cumulative incidence was higher for blacks than for whites and Hispanics, but more deaths occurred among incident black cases. Discrepant prevalence and incidence rates of Parkinson's disease among blacks and women warrant further investigation. While selective mortality could partially account for this paradox, it is also possible that a delay in diagnosis due to limited access to appropriate health services among these individuals could have resulted in the observed discordant rates of disease.

Age Distribution↗