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Biomedical subjects

R Mayeux

Publications and source records attributed to R Mayeux.

At least 91 records · Page 5Linked to original sources
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↗
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 apo E polymorphism with plasma lipid levels in a multiethnic elderly population.

Apolipoprotein E polymorphisms are important determinants of blood lipid levels and have been associated with longevity and atherosclerosis. However, information is limited on the effects of apo E variation on the lipids of nonwhite and elderly individuals. We tested the hypothesis that apo E polymorphisms are associated with plasma lipid levels in an elderly, multiethnic population. Cross-sectional data from 1068 noninstitutionalized individuals from northern Manhattan over the age of 64 who were not on a lipid-lowering diet or drug were analyzed. The ethnic distribution was 34% African-Americans, 47% Hispanics, and 19% non-Hispanic Caucasians. In the entire group, the most prevalent apo E allele was epsilon 3 (76%), followed by epsilon 4 (16%) and epsilon 2 (8%); epsilon 4 was more prevalent in African-Americans (21%) than in non-Hispanic Caucasians (12%) or Hispanics (14%). The apo epsilon 2 allele was the most important correlate of plasma lipids, but association varied across ethnoracial groups. After being adjusted for age, sex, obesity, diabetes mellitus, and alcohol intake, LDL cholesterol levels declined with each apo epsilon 2 allele by 8.8 mg/dL in Hispanics and by 25.6 and 18.1 mg/dL in non-Hispanic Caucasians and African-Americans, respectively (P < .001). No significant independent effect was noted for any apo E genotype on HDL cholesterol. Overall, there was a reduction in the total/HDL cholesterol ratio, per apo epsilon 2 allele, of 0.82 in non-Hispanic Caucasians and 0.43 and 0.48 in African-American and Hispanic individuals, respectively (P < .05). In a multivariate model, apo epsilon 4 did not significantly affect plasma lipid levels. Plasma triglyceride levels were inversely correlated with the number of apo epsilon 4 alleles (175, 159, and 143 mg/dL with 0, 1, and 2 alleles, respectively; P =.002), and this effect increased with age. Thus, in an elderly, multiethnic population, apolipoprotein E polymorphisms were important determinants of blood lipids, with differing effects depending on ethnicity. The presence of apo epsilon 2 was associated with lower LDL cholesterol levels and total/HDL cholesterol ratio, although apo epsilon genotype did not influence HDL cholesterol levels. Prospective studies are needed to test whether apo epsilon 2 protects against incident cardiovascular disease in the elderly.

Age Factors↗
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 age, ethnicity, and head injury on the association between APOE genotypes and Alzheimer's disease.

The association between apolipoprotein E (APOE)-epsilon 4 and Alzheimer's disease has been confirmed worldwide. We and others have observed a diminished association in the very old and among African-Americans compared to Caucasians and Hispanics in New York. In this review we describe a new method we developed to compare relative risks by APOE genotypes in an expanded cohort of cases and controls from three ethnic groups in a New York City community and discuss the association as between APOE epsilon 4 and Alzheimer's disease as modified by head injury. Compared to persons with APOE epsilon 3/epsilon 3 genotypes, relative risk (RR) for Alzheimer's disease associated with APOE epsilon 4 homozygosity was similar across ethnic groups (African-American RR = 3.3; 95% c.i. 1.6-6.8; Caucasian RR = 5.3; 1.6-16.0; Hispanic RR = 2.5; 1.1-5.8). The risk was also increased for APOE epsilon 4 heterozygous Caucasians (RR = 3.2; 1.8-5.8) and Hispanics (RR 1.5; 1.0-2.2) but not African-Americans (RR = 0.6; 0.4-0.9). Risk of AD was not significantly diminished for individuals in any group with APOE epsilon 2/epsilon 2 or -epsilon 2/epsilon 3 genotypes. A 10-fold increase in the risk of Alzheimer's disease was associated with both APOE epsilon 4 and a history of traumatic head injury, compared to a twofold increase in risk with APOE epsilon 4 alone. Head injury in the absence of an APOE epsilon 4 allele did not increase risk. These results imply that in Alzheimer's disease genotypic risk associated with APOE may be influenced by age, ethnicity, and certain environmental factors.

Black or African American↗
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

Depressed mood and the incidence of Alzheimer's disease in the elderly living in the community.

BACKGROUND: It remains unclear whether depression increases the risk for dementia in the elderly. We evaluated the relationship between depressed mood at baseline and the incidence of dementia, particularly Alzheimer's disease, in the elderly living in the community. METHODS: A total of 1070 elderly individuals, aged 60 years or older, were identified as part of a registry for dementia in the Washington Heights community of North Manhattan, NY. In a prospective, longitudinal design with follow-up for 1 to 5 years, annual physician evaluation and neuropsychological testing were used to assess levels of cognitive impairment and to diagnose dementia. Depressive symptoms were evaluated with the 17-item Hamilton Rating Scale for Depression. Based on clinical considerations and a validity study, a positive score for the depressed mood item was used in statistical analyses. To confirm the results, the total Hamilton Rating Scale for Depression score was also evaluated as the "depression" variable. RESULTS: Of the 1070 subjects, 218 met criteria for dementia at baseline evaluation. In the 852 subjects without dementia, depressed mood was more common in individuals with greater cognitive impairment. In a follow-up study of 478 of these subjects without dementia (mean +/- SD, 2.54 +/- 1.12 years of follow-up), the effect of baseline depressed mood on the end-point diagnosis of dementia (93% had possible or probable Alzheimer's disease) was evaluated in a Cox proportional hazards model. Depressed mood at baseline was associated with an increased risk of incident dementia (relative risk, 2.94; 95% confidence interval, 1.76 to 4.91; P < .001). This effect remained after adjustment for age, gender, education, language of assessment, Blessed Memory Information and Concentration test scores, and Blessed Functional Activity Scale scores (relative risk, 2.05; 95% confidence interval, 1.16 to 3.62; P < .02). Similar results were obtained when the total Hamilton Rating Scale for Depression score was used as the depression variable, with the use of the same covariates (relative risk, 1.07 per point interval; 95% confidence interval, 1.02 to 1.11; P < .01). CONCLUSIONS: Depressed mood moderately increased the risk of developing dementia, primarily Alzheimer's disease. Whether depressed mood is a very early manifestation of Alzheimer's disease, or increases susceptibility through another mechanism, remains to be determined.

Age Factors↗
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

Onset of dementia is associated with apolipoprotein E epsilon4 in Down's syndrome.

We examined the influence of apolipoprotein E (apoE) genotype on risk of dementia in 82 adults with Down's syndrome (DS). Compared with those with an apoE 3/3 genotype, the group of adults with DS with apoE 2/4, 3/4, and 4/4 genotypes were 5 times more likely to become demented (RR = 4.7; 95% CI = 1.2, 17.9). We hypothesize that the increased risk of dementia may be mediated by exacerbation of beta-amyloid deposition.

Adult↗
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

Polymorphisms in the human apolipoprotein-J/clusterin gene: ethnic variation and distribution in Alzheimer's disease.

Apolipoprotein-J/clusterin (APOJ/CLI) shares many biological properties with apolipoprotein-E (APOE) including, but not limited to, avid binding with beta-amyloid peptide. Thus, APOJ/CLI warrants scrutiny as a candidate Alzheimer's disease (AD) susceptibility gene. We identified seven nucleotide sequence polymorphisms in APOJ/ CLI, two of which, in exon 7, after the predicted amino acid sequence. The JVIIB variant is an asparagine-to-histidine substitution, which deletes a glycosylation signal at amino acid 317; the JVIIC variant is an aspartate-to-asparagine substitution, which forms a new glycosylation signal at position 328. Both of these coding variants, as well as two neutral polymorphisms in exon 2, were more frequent in African-Americans than Hispanics and were rare in Caucasians. However, no individual coding or noncoding variant was consistently associated with AD. At the population level, APOJ/CLI polymorphisms are frequent among persons of African descent, but probably do not alter susceptibility to AD.

Black or African American↗
PubMed1996

Development of a national prospective study of Alzheimer disease.

The purpose of this commentary is briefly to review the genetic, social, demographic, and environmental factors associated with Alzheimer disease with the specific purpose of planning an intervention to prevent or possibly delay the onset of disease. Complex disorders such as Alzheimer disease are the result of one or more genes and other contributing risk factors. For example, apolipoprotein E (APOE) genotypes can indicate a degree of susceptibility, but the gene is neither "necessary nor sufficient" to cause the disease. Thus, many potential risk factors remain to be identified. The association between Alzheimer disease and APOE also varies with age, genetic background, and ethnic group. While the use of APOE genotyping has provided a method to identify individuals at greatest risk of Alzheimer disease, how other factors modify the degrees of the APOE-related risk needs to be further investigated. Moreover, the effect of APOE on disease course and various noncognitive manifestations warrant scrutiny. Because risk prediction is not straightforward, practical issues related to developing a national strategy to prevent or delay the onset of Alzheimer disease require careful consideration, planning, and an organized interdisciplinary effort.

Alzheimer Disease↗
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

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↗