Biomedical subjects

K Marder

Publications and source records attributed to K Marder.

At least 73 records · Page 4Linked to original sources

PubMed1999

Functional significance of mild cognitive impairment in elderly patients without a dementia diagnosis.

The authors investigated differences in functional ability among three groups of subjects who were not diagnosed with dementia: normal control (NC) subjects (n=35); Clinical Dementia Rating Scale (CDRS) score of 0 (minimal impairment; n=26); and CDRS 0. 5 (questionable dementia; n=42). CDRS 0 and 0. 5 patients reported significantly poorer functioning than NCs in household and other activities, but CDRS 0 and CDRS 0. 5 groups did not differ in self-reported functioning. It is likely that CDRS 0. 5 patients overestimated their functional abilities. Correlations between self- and informant reports of functional status were significantly lower in the CDRS 0. 5 group than in the CDRS 0 group, an important finding for clinical management because patients with questionable dementia may actually be more impaired than they admit. Informants' reports or standardized performance-based assessment should be considered in the clinical evaluation of such patients.

Activities of Daily Living↗

PubMed1998

Characterization of the human mitochondrial aconitase gene (ACO2).

We have cloned and characterized the ACO2 gene on human chromosome 22q13, which encodes the essential iron-dependent metabolic enzyme mitochondrial aconitase. We determined that the ACO2 gene comprises 18 translated exons distributed over approximately 35 kilobasepairs (kbp) of DNA. We have shown that the ACO2 mRNA is 2.7kb in length and is expressed ubiquitously, and we can detect multiple isoforms of the ACO2 protein. As others had reported the existence of biochemically active electrophoretic variants of mitochondrial aconitase, we wished to find common ACO2 gene allozymes, functional polymorphisms that might be associated with susceptibility to human genetic diseases. We looked for ACO2 allozymes by DNA sequencing and genotyping in a population of 217 subjects, many of which had idiopathic Parkinson's disease (IPD). We studied patients with IPD because this movement disorder is thought to arise from defects in neuronal iron and energy metabolism, two properties with which aconitase is involved. Furthermore, reports of associations between alleles of the CYP2D6 locus (nearby on 22q13) and IPD, although inconsistent, indicated that an IPD susceptibility locus might be in strong linkage disequilibrium with CYP2D6. We found three functionally silent single nucleotide polymorphisms (SNPs) present in transcribed sequences that exist in similar frequencies in IPD patients and healthy controls. These ACO2 SNPs are in linkage disequilibrium with each other, providing evidence for distinct ACO2 haplotypes. We have, as yet, not detected polymorphisms that would lead to ACO2 allozymes, nor have we observed differences in ACO2 isoform prevalence or distribution in our population of IPD patients and controls. We conclude it is unlikely that polymorphism in the ACO2 gene or post-translational modification of the enzyme predispose to IPD.

Aconitate Hydratase↗

PubMed1998

The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics.

CONTEXT: Although the association between Alzheimer disease (AD) and the apolipoprotein E epsilon4 (APOE-epsilon4) allele has been confirmed worldwide, it appears to be inconsistent among African Americans, Hispanics, and Nigerians. OBJECTIVE: To investigate the association between the APOE-epsilon4 allele and AD in elderly African Americans, Hispanics, and whites. DESIGN: Prospective, population-based, longitudinal study over a 5-year period (1991-1996). SETTING: The Washington Heights-Inwood community of New York City. PARTICIPANTS: A total of 1079 Medicare recipients without AD or a related disorder at baseline. MAIN OUTCOME MEASURES: Risk of clinically diagnosed AD in the 3 ethnic groups and among individuals with and without an APOE-epsilon4 allele. RESULTS: Compared with individuals with the APOE-epsilon3/epsilon3 genotype, the relative risk (RR) of AD associated with 1 or more copies of the APOE-epsilon4 allele was significantly increased among whites (RR, 2.5; 95% confidence interval [CI], 1.1-6.4), but not among African Americans (RR, 1.0; 95% CI, 0.6-1.6) or Hispanics (RR, 1.1; 95% CI, 0.7-1.6). In the absence of the APOE-epsilon4 allele, the cumulative risks of AD to age 90 years, adjusted for education and sex, were 4 times higher for African Americans (RR, 4.4; 95% CI, 2.3-8.6) and 2 times higher for Hispanics (RR, 2.3; 95% CI, 1.2-4.3) than for whites. In the presence of an APOE-epsilon4 allele, the cumulative risk of AD to age 90 years was similar for individuals in all 3 ethnic groups. CONCLUSION: The presence of an APOE-epsilon4 allele is a determinant of AD risk in whites, but African Americans and Hispanics have an increased frequency of AD regardless of their APOE genotype. These results suggest that other genes or risk factors may contribute to the increased risk of AD in African Americans and Hispanics.

Aged↗

PubMed1998

Validity of family history for the diagnosis of dementia among siblings of patients with late-onset Alzheimer's disease.

We examined 180 siblings of 127 probands with probable or possible Alzheimer's dementia (AD) in a family study of AD. The overall sensitivity of a simple family history questionnaire was 64% and the specificity was 84%. Sensitivity improved 90-100% with minimal decline in specificity when we considered clinic-based vs. population survey patients. Higher education among informants and the availability of a spouse or a sibling as informant significantly increased sensitivity. Awareness of such factors may improve the yield of the family history in AD using a simple questionnaire.

Age of Onset↗

PubMed1998

A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease.

OBJECTIVE: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. METHOD: In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. RESULTS: For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS: The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors.

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PubMed1998

Environmental risk factors for Parkinson's disease in an urban multiethnic community.

Environmental risk factors were examined using univariate and multivariate unconditional logistic regression models in 89 nondemented patients with Parkinson's disease (PD) and 188 control subjects in a multiethnic urban community. Rural living, area farming, and drinking well water were associated with PD only in African-Americans. In Hispanics, area farming was protective, whereas drinking unfiltered water was a risk factor for PD. Consideration of ethnic and cultural origin may add to the epidemiologic study of PD.

Aged↗

PubMed1998

Cognitive function in nondemented older women who took estrogen after menopause.

Investigations of the effects of estrogen replacement on cognitive function in healthy older women have yielded disparate results. We evaluated the relationship between a history of estrogen use and cognitive test performance in 727 women participating in a large community-based study. Participants were followed longitudinally for an average of 2.5 years. Estrogen use history was obtained at baseline. Standardized tests of memory, language, and abstract reasoning were administered at baseline and at follow-up. Results indicate that women who had used estrogen replacement scored significantly higher on cognitive testing at baseline than nonusers, and their performance on verbal memory improved slightly over time. The effect of estrogen on cognition was independent of age, education, ethnicity, and APOE genotype. Results suggest that estrogen replacement therapy may help to maintain cognitive function in nondemented postmenopausal women.

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PubMed1998

Systemic iron metabolism and mortality from Parkinson's disease.

Six measures of systemic iron metabolism were used to predict mortality among 103 patients with Parkinson's disease and 353 controls followed in a longitudinal study. Adjusting for gender, education, ethnicity, presence of dementia, and extrapyramidal signs, transferrin receptor concentration was strongly associated with mortality in patients with PD but not controls. This increase in serum transferrin receptor concentration before death suggests that the previously observed perturbation in iron metabolism continues throughout the disease course.

Aged↗

PubMed1998

Postmenopausal estrogen use and Parkinson's disease with and without dementia.

We investigated the effects of estrogen replacement therapy (ERT) on the risk of development of dementia in 87 women with Parkinson's disease without dementia (PDND), 80 women with Parkinson's disease with dementia (PDD), and 989 nondemented healthy women from the same community. ERT was protective for the development of dementia within the setting of PD (OR 0.22, 95% CI 0.05-1.0) and when PDD patients were compared with controls (OR 0.24, 95% CI 0.07-0.78), but did not affect the risk of PD. The results of the study suggest that a randomized clinical trial of ERT may be warranted.

Aged↗

PubMed1998

Sexual risk behavior changes among HIV+ and HIV-female injecting drug users over 4 years.

This paper examines the sexual risk behavior of female injecting drug users who participated in a 4 year longitudinal study. Both HIV+ and HIV- women showed increases in monogamy, decreases in the frequency of unprotected vaginal/anal sex, and decreases in a risk index score throughout the study. HIV+ women had fewer occasions of unprotected sex than HIV-. However, a substantial proportion of the sample continued to engage in unprotected sex. Among the HIV+ women, depressed mood was significantly related to abstinence and to fewer occasions of unprotected sex, but CD4, medical symptoms, neurological impairment, and memory test performance were not associated with sexual risk behavior.

Adult↗

PubMed1998

Dietary iron, animal fats, and risk of Parkinson's disease.

BACKGROUND: Recent studies have proposed a role for diet in Parkinson's disease (PD). PD is characterized by a high deposition of iron and a low concentration of ferritin in the substantia nigra. Few data in the literature are available on the possible role of dietary iron in the development of PD. METHODS: In a population-based, case-control study, we addressed the hypothesis that high dietary iron intake was associated with PD. We assessed dietary iron intake with a semiquantitative food-frequency questionnaire in 104 PD patients and 352 control subjects, frequency matched for age and gender. We also studied the association of PD and dietary iron and animal fat intake in the presence of different iron stores measured by transferrin saturation. RESULTS: No significant differences were observed between patients' and control subjects' dietary intake of iron from food or supplements (odds ratio [OR] for the highest quartile of intake, 0.9; 95% confidence interval [95% CI], 0.6, 1.3; p for trend = 0.60). Among those with low transferrin saturation levels (lower 50%), the odds ratio for PD associated with animal fat intake was ninefold higher than the risk of those with low intake (OR, 9.0; 95% CI, 2.7-29.9). Among those with high transferrin saturation, risk of PD was two times higher (relative risk, 1.9; 95% CI, 0.5-7.2) for those who reported high intake of animal fat compared with those who reported low intake. CONCLUSION: Dietary iron intake after caloric adjustment was not associated with an increased risk of PD. However, the previously described association between animal fat intake and PD was modified by iron level stores as measured by transferrin saturation. These observations suggest that dietary fat and a systemic defect in iron metabolism may act synergistically in the process of lipid peroxidation in PD.

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PubMed1998

Prospective comparative study of the evolution of probable Alzheimer's disease and Parkinson's disease dementia.

No previous comparison of test performance in probable Alzheimer's disease (pAD) and Parkinson's disease (PD) dementia has provided information about potential differences in the dementing process. This study compared the evolution of cognitive changes associated with these dementias. Generalized estimating equations (GEE) applied to regression analyses with repeated measures were used to evaluate cognitive changes over 1 to 3 years prior to the point when dementia was diagnosed in 40 matched pairs of patients with incident pAD and PD dementia. Both groups' performance declined on the Short Blessed, Selective Reminding Test (SRT; total recall, long-term retrieval, and delayed recall), Boston Naming Test, Category Fluency, and Similarities. The decline on naming and SRT delayed recall was more rapid in the PD dementia group, suggesting that these performance deficits emerge earlier in the development of pAD. The PD dementia group performed worse on Category Fluency throughout the follow-up period, suggesting either that dementia is overlaid on this preexisting performance deficit or that this type of executive deficit is an early manifestation of dementia in PD. The pAD group performed more poorly throughout the follow-up period on SRT delayed recognition, consistent with a pAD-specific encoding deficit. We conclude that while pAD and PD dementia are similar in many respects, differences in their evolution support previous observation of unique features in the 2 dementias and suggest different underlying pathologies.

Aged↗

PubMed1997

Predicting time to nursing home care and death in individuals with Alzheimer disease.

OBJECTIVE: To develop and validate an approach that uses clinical features that can be determined in a standard patient visit to estimate the length of time before an individual patient with Alzheimer disease (AD) requires care equivalent to nursing home placement or dies. DESIGN: Prospective cohort study of 236 patients, followed up semiannually for up to 7 years. A second validation cohort of 105 patients was also followed. SETTING: Three AD research centers. PATIENTS: All patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD and had mild dementia at the initial visit. INTERVENTION: Predictive features, ascertained at the initial visit, were sex, duration of illness, age at onset, modified Mini-Mental State Examination (mMMS) score, and the presence or absence of extrapyramidal signs or psychotic features. MAIN OUTCOME MEASURES: (1) Requiring the equivalent of nursing home placement and (2) death. RESULTS: Prediction algorithms were constructed for the 2 outcomes based on Cox proportional hazard models. For each algorithm, a predictor index is calculated based on the status of each predictive feature at the initial visit. A table that specifies the number of months in which 25%, 50%, and 75% of patients with any specific predictor index value are likely to reach the end point is then consulted. Survival curves for time to need for care equivalent to nursing home placement and for time to death derived from the algorithms for selected predictor indexes fell within the 95% confidence bands of actual survival curves for patients. When the predictor variables from the initial visit for the validation cohort patients were entered into the algorithm, the predicted survival curves for time to death fell within the 95% confidence bands of actual survival curves for the patients. CONCLUSIONS: The prediction algorithms are a first but promising step toward providing specific prognoses to patients, families, and practitioners. This approach also has clear implications for the design and interpretation of clinical trials in patients with AD.

Age of Onset↗

PubMed1997

Mortality from Parkinson disease.

BACKGROUND: Levodopa therapy for Parkinson disease (PD) has improved quality of life, but mortality rates remain high. Although the presence of dementia and severity of extrapyramidal signs (EPSs) influence morbidity in PD, it is not known whether these manifestations contribute to mortality. METHODS: Patients with PD were compared with nondemented and demented elderly subjects. Each underwent annual neurological and neuropsychological examinations. Dementia was diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria, and EPSs were rated with the Unified Parkinson's Disease Rating Scale. Survival rates were compared using Kaplan-Meier analysis and Cox proportional hazards models. RESULTS: The risk of mortality, when compared with nondemented elderly subjects, was highest among those with both PD and dementia (rate ratio, 4.9; 95% confidence interval, 3.4-7.1), but also was elevated in patients with PD only (rate ratio, 2.7; 95% confidence interval, 1.7-4.4). Dementia in the absence of PD also was associated with an increased risk of mortality (rate ratio, 1.6; 95% confidence interval, 1.1-2.3). A high baseline total EPS score was associated with significantly earlier mortality. CONCLUSIONS: Compared with nondemented elderly people in the same community, patients with PD have a 2- to 5-fold increased risk of mortality. The risk is strongly related to the presence of severe EPSs, especially bradykinesia. Despite the introduction of levodopa and other advances in the treatment of PD, these factors greatly increase mortality.

Aged↗

PubMed1997

The validity of new memory complaints in the elderly.

OBJECTIVE: To determine the validity of new subjective memory complaints (MCs) from individuals who previously, when without dementia, denied having MCs. DESIGN: Prospective cohort. SETTING: Longitudinal, community-based study of aging and dementia. PATIENTS: One hundred thirty-three community-dwelling elderly individuals who were part of a registry for the study of conditions related to aging in North Manhattan, NY. Patients were selected if they were initially without dementia and had completed at least 2 successive annual clinical and neuropsychological evaluations and provided their own medical history. MAIN OUTCOME MEASURES: Performance on memory tests--the Buschke Selective Reminding Test and a visual memory task--and global performance on a neuropsychological test battery and clinical evaluation, by which questionable dementia or dementia was diagnosed according to a well-defined paradigm. RESULTS: Fifty-three subjects with MCs at the initial evaluation performed no worse on the memory test than the 80 subjects who denied MCs initially. There was a weak association between MCs and the diagnosis of questionable dementia at baseline (P = .04), but this was nonsignificant after adjusting for age and education. At 1-year follow-up, 21 of the 80 without baseline MCs now reported MCs. At the follow-up evaluation, these 21 subjects performed significantly worse on the memory tests, were 5 times more likely to have significant cognitive impairment, and had shown significantly greater decline over the preceding year on several of the cognitive measures than the 59 who continued to deny MCs. CONCLUSION: New MCs from individuals, who when without dementia recently denied MCs, may suggest the presence of significant impairment of memory or cognition.

Aged↗

PubMed1997

The course of psychopathologic features in mild to moderate Alzheimer disease.

BACKGROUND: The onset and course of the psychopathologic features of Alzheimer disease have not been established in prospective, longitudinal studies. METHODS: Two hundred thirty-five patients with early, probable Alzheimer disease were recruited at 3 sites and observed naturalistically for up to 5 years. At 6-month intervals, the Columbia University Scale for Psychopathology in Alzheimer's Disease was administered. Markov analyses were used to predict the probability of a specific symptom developing or being maintained at the next visit. For each symptom category, the maximum frequency of occurrence at 4 consecutive points (duration, 2 years) was calculated. RESULTS: Misidentification, wandering or agitation, and physical aggression increased during follow-up. At any visit, the likelihood of a new symptom developing was greatest for behavioral disturbance, intermediate for paranoid delusions and hallucinations, and least for depressed mood with vegetative features. Wandering or agitation occurred at 3 or more of 4 consecutive visits (duration, 2 years) in the majority of patients, paranoid delusions and hallucinations were intermediate in their degree of persistence, and depressed mood with vegetative signs rarely persisted. CONCLUSIONS: Behavioral disturbance, particularly agitation, is common and persistent in patients with Alzheimer disease. Psychotic symptoms are less common and show moderate persistence over time. Depressed mood with vegetative signs is uncommon and rarely persists. These findings suggest leads about the optimal treatment duration for specific subtypes of psychopathologic features.

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PubMed1997

The absence of an apolipoprotein epsilon4 allele is associated with a more aggressive form of Alzheimer's disease.

We investigated the relationship between APOE genotype and rate of disease progression and survival in 99 patients with probable Alzheimer's disease (AD) who were followed biannually for up to 6 years. Patients were stratified into two groups, those with and without at least one APOE epsilon4 allele. The rate of decline in modified Mini-Mental State Examination scores was slower, the presence of extrapyramidal signs was decreased, and the development of myoclonus occurred later among patients with APOE epsilon4 alleles compared with patients with other genotypes. Compared with patients without an APOE epsilon4 allele, the risk of mortality was also decreased in patients with at least one epsilon4 allele (RR = 0.38; CI = 0.17-0.84, p < 0.02). Because the decline in mental ability as well as the development of myoclonus and extrapyramidal signs are consistent manifestations of disease progression, our results imply that APOE epsilon4 is associated with a less aggressive form of AD.

Age of Onset↗

PubMed1997

Is there a genetic susceptibility locus for Parkinson's disease on chromosome 22q13?

The cytochrome P450 mono-oxygenase gene, CYP2D6 on chromosome 22q13 (ch22q13), has been inconsistently associated with Parkinson's disease. Associations with CYP2D6 have either been absent altogether or have involved more than one polymorphism, many of which have the same metabolic effect on gene expression. We examined the association between CYP2D6 polymorphisms and Parkinson's disease in a case-control study and included 10 polymorphic dinucleotide repeat markers linked to CYP2D6 to determine whether the association was present or due to linkage disequilibrium. There was no association between any polymorphism of CYP2D6 and Parkinson's disease, but two of 10 dinucleotide repeat markers linked to CYP2D6 were associated with the disease. These results provide evidence to suggest that there may be an unidentified locus for susceptibility to Parkinson's disease that is in linkage disequilibrium with dinucleotide repeat markers mapping near CYP2D6 on ch22q13.

Adult↗