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Biomedical subjects

Richard Mayeux

Publications and source records attributed to Richard Mayeux.

At least 37 records · Page 2Linked to original sources
PubMed2005

Atherosclerosis and AD: analysis of data from the US National Alzheimer's Coordinating Center.

BACKGROUND: Epidemiologic studies have implicated cerebrovascular disease and its antecedents as risk factors for Alzheimer disease (AD). Cerebral atherosclerosis or strokes may increase the deposition of neuritic plaques or the formation of neurofibrillary tangles. Alternatively, they may simply hasten the age at onset of disease, or increase the severity of disease symptoms. This investigation examined the association between cerebrovascular disease and the pathologic manifestations of AD in an autopsy series. METHODS: This was a cross-sectional study using data from the United States National Alzheimer's Coordinating Center database. The primary analysis included 1,054 individuals with clinical information and semiquantitative neuropathologic measurements: 921 had AD as the primary neuropathologic diagnosis and 133 were considered neuropathologically normal. RESULTS: Overall, 9% of the individuals had clinical history of stroke during life, but 33% had evidence of cerebral infarcts at postmortem. There was no association between neuritic plaques or neurofibrillary tangles, the primary neuropathologic manifestations of AD, with either clinical history of stroke or the presence of cerebral infarcts at postmortem. The authors did find a higher frequency of neuritic plaques and neurofibrillary tangles with increased amyloid angiopathy. Neither plaques nor tangles were associated with small vessel cerebrovascular disease, arteriosclerosis. However, the presence of large-vessel cerebrovascular disease, or atherosclerosis, was strongly associated with an increased frequency of neuritic plaques. CONCLUSIONS: Atherosclerotic cerebrovascular disease may have a role in the pathogenesis of Alzheimer disease, because of a strong association with frequent neuritic plaques.

Age of Onset↗
PubMed2005

Implementing diagnostic criteria and estimating frequency of mild cognitive impairment in an urban community.

BACKGROUND: Reported rates of mild cognitive impairment (MCI) range widely depending on methodologic differences, including specific sample characteristics, cognitive measures used, normative samples used for neuropsychological tests, and diagnostic criteria. OBJECTIVES: To operationalize diagnostic criteria for MCI and examine the frequency of MCI in ethnically and linguistically diverse elders (individuals older than 65 years). DESIGN: Prospective, community-based longitudinal cohort study. SETTING: Northern Manhattan, New York, NY. PARTICIPANTS: A cohort of 1315 nondemented elderly participants. MAIN OUTCOME MEASURE: A diagnosis of MCI was assigned retrospectively on the basis of comprehensive neuropsychological, functional, and neurologic assessments. Amnestic MCI, as well as forms of mild impairment with other cognitive characteristics, were classified. RESULTS: The frequency of amnestic MCI was 5.0% (95% confidence interval, 3.8-6.2). Other subtypes of MCI ranged in frequency from 2.1% to 6.2%. Mild cognitive impairment was more common among those older than 75 years compared with those aged 65 to 75 years. Individuals with fewer than 9 years of schooling were more likely to meet MCI criteria. Apolipoprotein (APOE) E4 allele was more frequent among those with amnestic MCI. CONCLUSIONS: When proper normative values are used, only age and education, and not race or ethnicity, are associated with higher frequency of MCI. The proportion of nondemented elders with isolated memory deficits is smaller than the proportion with deficits in multiple cognitive domains. The strong association of the APOE E4 allele with only amnestic MCI suggests that there are likely to be multiple causes of cognitive impairment and differential rates of conversion to Alzheimer disease within the cognitive subtypes of MCI.

Activities of Daily Living↗
PubMed2005

Functional correlates and prevalence of mild parkinsonian signs in a community population of older people.

BACKGROUND: Mild parkinsonian signs (MPS) are associated with incident dementia and an increased risk of mortality. To our knowledge, the functional correlates of MPS have not been studied. OBJECTIVES: To study the functional correlates of MPS, including self-reported and performance-based measures of function, and to determine the prevalence of MPS in a cohort of community-dwelling older people (aged >or=65 years). DESIGN: Participants (N = 1866) in the Washington Heights-Inwood Columbia Aging Project underwent a neurological assessment that included a modified motor portion of the Unified Parkinson's Disease Rating Scale, which yielded a parkinsonian sign score (range, 0-40) and parkinsonian sign subscores (axial function, rigidity, and tremor). A functional assessment included 3 self-reported measures of function and 2 performance-based tests. Participants with Parkinson disease were excluded. RESULTS: Mild parkinsonian signs were present in 469 (25.1%) of the 1866 participants. The parkinsonian sign score was correlated with functional and performance-based test scores (r = 0.24-0.32, P<.001). The axial function and rigidity subscores correlated to a greater extent with functional and performance-based test scores than did the tremor subscore. In analysis of covariance models, excluding participants with dementia and adjusting for age, sex, ethnicity, education, depressive symptoms, and medical illnesses (eg, arthritis), the parkinsonian sign score and age were strongly and independently associated with functional scores. CONCLUSIONS: Mild parkinsonian signs, and particularly axial dysfunction, were associated with functional disability, including self-reported and performance-based measures of functional difficulty. Given the high prevalence of these signs in elderly persons, MPS may be a significant indicator of disability in elderly persons.

Activities of Daily Living↗
PubMed2005

Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment.

BACKGROUND: In cognitively impaired patients without dementia, the utility of apolipoprotein E (APOE) genotyping is unclear. OBJECTIVE: To evaluate the predictive utility of the APOE epsilon4 genotype for conversion to probable Alzheimer disease (AD). DESIGN: Naturalistic, longitudinal study. SETTING: Memory disorders outpatient clinic. PATIENTS: A total of 136 patients with memory complaints were determined to have mild cognitive impairment and were evaluated every 6 months. Fifty-seven age- and sex-matched healthy controls were evaluated annually. MAIN OUTCOME MEASURES: Primary outcome measures included conversion to AD. Secondary outcome measures included change over time in Mini-Mental State Examination (MMSE) score and Selective Reminding Test (SRT) delayed recall score. RESULTS: The APOE epsilon4 allele was present in 25% of patients and 21% of healthy controls. During a mean +/- SD follow-up of 35.2 +/- 24.3 months, 35 of 136 patients converted to AD. APOE epsilon4 carrier status did not differ between converters (31%) and nonconverters to AD (23%, P = .3) and did not affect the time trend in MMSE or SRT scores in the entire sample. Four of 5 APOE epsilon4 homozygotes converted to AD compared with 7 of 29 heterozygotes (P = .02). In a Cox proportional hazards model stratified by age quartiles, after controlling for sex, education, MMSE score, and SRT delayed recall score, APOE epsilon4 increased the risk of AD in patients 70 to 85 years old (n = 57; risk ratio, 2.77; 95% confidence interval, 1.1-7.3; P = .03) but not in patients 55 to 69 years old (n = 79; P = .7). CONCLUSIONS: APOE epsilon4 carrier status was associated with conversion to AD in older outpatients after controlling for known demographic and clinical risk factors, and APOE epsilon4 homozygosity was associated with increased risk of conversion to AD. However, APOE epsilon4 carrier status by itself did not predict cognitive decline or conversion to AD, indicating that APOE genotyping in patients with mild cognitive impairment may have limited clinical applicability for prediction of outcome.

Aged↗
PubMed2005

Pilot association study of the beta-glucocerebrosidase N370S allele and Parkinson's disease in subjects of Jewish ethnicity.

Mutations in the beta-glucocerebrosidase gene cause Gaucher's disease, one of the most common lysosomal lipid storage diseases in the Ashkenazi Jewish population. The occurrence of parkinsonism in patients with Type 1 Gaucher's disease has been noted previously. In this pilot study, we evaluated a possible association between Parkinson's disease (PD) and the beta-glucocerebrosidase gene N370S allele (nt.1226 A>G) in 160 Parkinson's disease patients and 92 controls of Jewish ethnicity. We observed a higher frequency of the N370S genotype in PD cases (NS and SS, 10.7%) compared to controls (NS and SS 4.3%); however, the difference was not statistically significant (chi(2) = 3.4, P = 0.2). A total of 17 PD cases carry the N370S allele, including 2 homozygotes and 15 heterozygotes. The N370S allele (nt.1226 A>G) may be associated with PD in patients of Jewish ethnicity and should be examined in a larger study.

Aged↗
PubMed2005

Disparities in the recording of Parkinson's disease on death certificates.

Although little is known regarding potential socioeconomic or racial bias in the recording of Parkinson's disease (PD) on death certificates, studies of incidence, prevalence, and the etiology of PD frequently rely on this type of data. A national population-based survey was linked to death certificate data to investigate the concordance of PD reported on death certificates for persons reporting PD during life. Logistic regression was used to identify independent factors associated with differential reporting of PD at death. Among decedents with PD reported during life, 54.8% had PD recorded on the death certificate. Nearly 70% of persons in higher income categories had PD recorded at death compared to 35.4% for those earning $10,000 or less. Age and gender adjusted odds of having PD recorded at death was 2.3 (1.1-3.9), for those with an annual income of $35,000 or more. Income differences remain significant in multivariable models after controlling for age, gender, race, census region, family size, rural residence, and number of chronic medical conditions. In conclusion, this study found socioeconomic bias in the reporting of PD at death. This bias is large enough to confound death certificate-based investigations of incidence, prevalence, and risk factors that differ across socioeconomic strata.

Aged↗
PubMed2005

Medicaid home care services and survival in New York City.

PURPOSE: New York City's Medicaid Home Care Services Program provides an integrated program of housekeeping and personal assistance care along with regular nursing assessments. We sought to determine if this program of supportive care offers a survival benefit to older adults. DESIGN AND METHODS: Administrative data from New York City's Medicaid Home Care Services Program were merged with epidemiologic and diagnostic data collected in a community study of older adults living in northern Manhattan. Of 866 older adults with Medicaid coverage living in the community, 288 (33.3%) received Medicaid home care services in the period from 1994 to 1996. Mortality was tracked through the end of 1999. RESULTS: In proportional hazards models that adjusted for differences in sociodemographic, medical, and functional status, use of Medicaid home care service was associated with a significantly reduced risk of death in people with disability in activities of daily living. IMPLICATIONS: Because the program has distinctive features (greater number of weekly hours than other programs, integration with nursing assessments), it is a special case of community-based long-term care. Still, results from this observational cohort suggest that mortality risk in the most vulnerable elderly population can be reduced through a program of supportive care.

Activities of Daily Living↗
PubMed2005

Relationship between plasma lipids and all-cause mortality in nondemented elderly.

OBJECTIVES: To investigate the relationship between plasma lipids and risk of death from all causes in nondemented elderly. DESIGN: Prospective cohort study. SETTING: Community-based sample of Medicare recipients, aged 65 years and older, residing in northern Manhattan. PARTICIPANTS: Two thousand two hundred seventy-seven nondemented elderly, aged 65 to 98; 672 (29.5%) white/non-Hispanic, 699 (30.7%) black/non-Hispanic, 876 (38.5%) Hispanic, and 30 (1.3%) other. MEASUREMENTS: Anthropometric measures: fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-HDL-C, body mass index, and apolipoprotein E (APOE) genotype. clinical measures: neuropsychological, neurological, medical, and functional assessments; medical history of diabetes mellitus, heart disease, hypertension, stroke, and treatment with lipid-lowering drugs. Vital status measure: National Death Index date of death. Survival methods were used to examine the relationship between plasma lipids and subsequent mortality in younger and older nondemented elderly, adjusting for potential confounders. RESULTS: Nondemented elderly with levels of total cholesterol, non-HDL-C, and LDL-C in the lowest quartile were approximately twice as likely to die as those in the highest quartile (rate ratio (RR)=1.8, 95% confidence interval (CI)=1.3-2.4). These results did not vary when analyses were adjusted for body mass index, APOE genotype, diabetes mellitus, heart disease, hypertension, stroke, diagnosis of cancer, current smoking status, or demographic variables. The association between lipid levels and risk of death was attenuated when subjects with less than 1 year of follow-up were excluded (RR=1.4, 95% CI=1.0-2.1). The relationship between total cholesterol, non-HDL-C, HDL-C, and triglycerides and risk of death did not differ for older (>or=75) and younger participants (>75), whereas the relationship between LDL-C and risk of death was stronger in younger than older participants (RR=2.4, 95% CI=1.2-4.9 vs RR=1.6, 95% CI=1.02-2.6, respectively). Overall, women had higher mean lipid levels than men and lower mortality risk, but the risk of death was comparable for men and women with comparable low lipid levels. CONCLUSION: Low cholesterol level is a robust predictor of mortality in the nondemented elderly and may be a surrogate of frailty or subclinical disease. More research is needed to understand these associations.

Aged↗
PubMed2005

Mapping the new frontier: complex genetic disorders.

The remarkable achievements in human genetics over the years have been due to technological advances in gene mapping and in statistical methods that relate genetic variants to disease. Nearly every Mendelian genetic disorder has now been mapped to a specific gene or set of genes, but these discoveries have been limited to high-risk, variant alleles that segregate in rare families. With a working draft of the human genome now in hand, the availability of high-throughput genotyping, a plethora of genetic markers, and the development of new analytical methods, scientists are now turning their attention to common complex disorders such as diabetes, obesity, hypertension, and Alzheimer disease. In this issue, the JCI provides readers with a series dedicated to complex genetic disorders, offering a view of genetic medicine in the 21st century.

Alleles↗
PubMed2004

Hyperinsulinemia and risk of Alzheimer disease.

OBJECTIVE: To explore the association between fasting insulin levels and dementia. METHODS: Fasting insulin levels were measured from frozen sera using solid-phase chemiluminescent enzyme immunoassay in a sample of elderly subjects chosen at random from a cohort of persons aged 65 years and older from northern Manhattan. Dementia was diagnosed using standard methods. Neuropsychiatric testing was available on all subjects at each follow-up interval. RESULTS: A total of 683 subjects without prevalent dementia were followed for 3,691 person-years and 149 persons developed dementia (137 Alzheimer disease [AD], 6 dementia associated with stroke, 6 other). The risk of AD doubled in the 39% of the sample with hyperinsulinemia (HR = 2.1; 95% CI: 1.5, 2.9) and was highest in people without diabetes. The HR relating presence of hyperinsulinemia or diabetes in 50% of our sample to AD was 2.2 (95% CI: 1.5, 3.1). The risk of AD attributable to the presence of hyperinsulinemia or diabetes was 39%. The HR of AD for the highest quartile of insulin compared to the lowest was 1.7 (95% CI: 1.0, 2.7; p for trend = 0.009). Hyperinsulinemia was also related to a significant decline in memory-related cognitive scores, but not to decline in other cognitive domains. CONCLUSIONS: Hyperinsulinemia is associated with a higher risk of AD and decline in memory.

Aged↗
PubMed2004

Genetic influences on life span and survival among elderly African-Americans, Caribbean Hispanics, and Caucasians.

An investigation of the genetic influences on life span and survival was conducted among elderly African-Americans, Caribbean Hispanics, and Caucasians Medicare recipients (ages 65-104 years). Family history information on 13,161 parents and siblings was obtained. Heritability of life span varied by the age and by ethnic group being lowest for African-Americans. We recalculated the heritability coefficients for life span including only probands and their siblings, but the differences across ethnic groups persisted. In contrast the heritability of survival was more similar across ethnic groups but was similar to that for life span. Heritability coefficients for survival in probands and their siblings revealed little difference between ethnic groups and suggested that as much as 35% of the variation in survival may be genetically influenced. These results indicate that life span and survival are genetically influenced. Comparisons across generations and ethnic groups indicate that changes in environmental hygiene, social welfare, and health care systems are significant contributors to life span and survival, but genetic influences are also important. Identifying the genes associated with life span and survival will provide insight into how the genes interact with environment to influence aging in humans.

Age Factors↗
PubMed2004

Relation of plasma lipids to Alzheimer disease and vascular dementia.

BACKGROUND: The relation between plasma lipid levels and Alzheimer disease (AD) and vascular dementia (VaD), and the impact of drugs to lower lipid levels remains unclear. OBJECTIVE: To investigate the relation between plasma lipid levels and the risk of AD and VaD and the impact of drugs to lower lipid levels on this relationship. DESIGN AND SETTING: Cross-sectional and prospective community-based cohort studies. PARTICIPANTS: Random sample of 4316 Medicare recipients, 65 years and older, residing in northern Manhattan, NY. MAIN OUTCOME MEASURES: Vascular dementia and AD according to standard criteria. RESULTS: Elevated levels of non-high-density lipoprotein (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and decreased levels of HDL-C were weak risk factors for VaD in either cross-sectional or prospective analyses. Higher levels of total cholesterol were associated with a decreased risk of incident AD after adjustment for demographics, apolipoprotein E genotype, and cardiovascular risk factors. Treatment with drugs to lower lipid levels did not change the disease risk of either disorder. CONCLUSIONS: We found a weak relation between non-HDL-C, LDL-C, and HDL-C levels and the risk of VaD. Lipid levels and the use of agents to lower them do not seem to be associated with the risk of AD.

Aged↗
PubMed2004

Parkinsonian signs in older people in a community-based study: risk of incident dementia.

BACKGROUND: Mild parkinsonian signs occur in 30% to 40% of community-dwelling older people. In a cross-sectional study, the severity of these signs was greater in people with dementia than in people without dementia. OBJECTIVE: To determine whether baseline mild parkinsonian signs are a predictor of incident dementia. DESIGN: A prospective, longitudinal study of community-dwelling older people who did not have dementia or Parkinson disease at baseline. METHODS: A neurological examination was performed on 1028 residents aged 65 years or older in the Washington Height-Inwood community in northern Manhattan, NY. Parkinsonian signs were rated with an abbreviated Unified Parkinson's Disease Rating Scale, resulting in a parkinsonian sign score (range, 0-40). The risk of incident dementia was assessed using Cox proportional hazards models. In some analyses, data from the modified Unified Parkinson's Disease Rating Scale were divided into 3 domains: rigidity, axial function, and tremor at rest. RESULTS: The mean duration of follow-up was 5.6 years, and 224 participants (21.8%) developed dementia. In a Cox model, the risk of incident dementia was 57% higher in participants with a baseline parkinsonian sign score of 2 vs 0 (relative risk, 1.56; 95% confidence interval, 1.04-2.33; P =.03). In a second Cox model, the baseline parkinsonian sign score was associated with incident dementia (relative risk, 1.08; 95% confidence interval, 1.01-1.16; P =.02) independent of associations with baseline age, education, ethnicity, diabetes mellitus, and stroke. CONCLUSIONS: Baseline mild parkinsonian signs are a predictor of incident dementia. Although these signs are mild, they are not prognostically benign. Brain imaging and postmortem examinations might further our insight into the anatomical and pathological basis for mild parkinsonian signs.

Aged↗
PubMed2004

APOE and APOC1 promoter polymorphisms and the risk of Alzheimer disease in African American and Caribbean Hispanic individuals.

BACKGROUND: The APOE epsilon4 allele is a genetic risk factor for Alzheimer disease (AD), though the strength of the association varies by ethnic group. Polymorphisms in regulatory sequences of APOE have also been related to AD, but the effects are inconsistent across studies. METHODS: We examined the association between AD and variants in 3 APOE promoters and in the promoter of the adjacent APOC1 gene in African American and Caribbean Hispanic individuals. Polymorphisms tested were the -491A/T, -427T/C, and -219G/T (Th1/E47cs) in the APOE promoter and the HpaI variant in the APOC1 promoter. Using standard research criteria for AD, overall odds ratios were computed and repeated stratified by presence or absence of APOE epsilon4. RESULTS: The APOC1 HpaI+ variant was associated with AD in Caribbean Hispanic individuals, but strong linkage disequilibrium with the APOE epsilon4 allele indicated that this was not an independent effect. No promoter variant in APOE or APOC1 was associated with AD before or after adjusting for age, education, sex, and multiple comparisons. Estimated haplotypes including -219G/T, APOE, and APOC1 differed significantly in Caribbean Hispanic patients and controls but not in African American participants. This effect was primarily owing to the -219G/T-APOE haplotype, but we did not detect significant allele-specific differences in promoter activity comparing reporter constructs containing the APOE -219G and -219 T alleles. CONCLUSION: These findings exclude a strong or independent influence of APOE or APOC1 promoter polymorphisms on the variation in APOE-related risk of AD in African American and Caribbean Hispanic individuals.

Black or African American↗
PubMed2004

Factor structure of parkinsonian signs in the community-dwelling elderly.

Parkinsonian signs are present in 40% of older people. Factor analysis of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with Parkinson's disease (PD) has identified several principal domains, including rigidity, axial function, and rest tremor. We hypothesized that if Parkinsonian signs in the elderly were due to basal ganglia dysfunction that this same constellation of factors (rigidity, axial function, rest tremor) would emerge in a factor analysis. We carried out factor analysis, using the principal component method with orthogonal (varimax) rotation, on motor UPDRS scores in community-dwelling elderly without PD. A modified (10-item) version of the motor portion of the UPDRS was administered to 1,339 older adults living in the Washington Heights-Inwood community and it was found that Parkinsonian signs were present in 537 (40.1%). Three factors (rigidity, axial function. and rest tremor) were obtained from the factor analysis and, together, explained 67.4% of the variance. A second factor analysis was carried out excluding the 26 participants with rest tremor, and two factors (rigidity, axial function) emerged. These data support the view that Parkinsonian signs in older adults might be due to basal ganglia dysfunction, a possibility that requires further exploration.

Adult↗
PubMed2004

Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations.

The frequency and relative contribution of DJ-1 mutations in early-onset Parkinson's disease (EOPD) is currently unknown. We analyzed a cohort of 89 EOPD patients (mean age at onset of PD +/- SD, 41.5 +/- 7.2 years), ascertained independent of family history, who participated in a study of the genetic epidemiology of PD. This study includes sequence analysis of the DJ-1 gene in addition to assaying the 14,082-bp deletion spanning exons 1 to 5, previously identified in a Dutch kindred, in 89 EOPD cases. A heterozygous missense mutation in exon 5 (A104T) was identified in an EOPD case of Asian ethnicity; this sequence variant was absent in 308 control chromosomes. We identified additional sequence variation in the DJ-1 gene, including a polymorphism in the coding region in exon 5 (R98Q), three polymorphisms in the 5' untranslated region (exon 1A/1B), and two polymorphisms in intronic regions (IVS1 and IVS5). Mutations in the DJ-1 gene are rare in EOPD in both sporadic and familial cases.

Adult↗
PubMed2004

Cardiovascular risk factors and Alzheimer's disease.

Alzheimer's disease is a devastating condition that is increasing in prevalence. No known prevention or cure exists for Alzheimer's disease. Cardiovascular risk factors are prevalent and increase in the elderly, and there have been conflicting reports of associations between modifiable cardiovascular risk factors and Alzheimer's disease. The mechanisms for these associations are uncertain, but they are likely to be the result of a combination of direct and cerebrovascular disease-related mechanisms. From this standpoint, diabetes and hyperinsulinemia seem to have the strongest evidence from laboratory, clinical, and epidemiologic studies. Studies have also indicated that hypertension, hyperlipidemia, hyperhomocysteinemia, and smoking are potentially important risk factors for Alzheimer's disease.

Alzheimer Disease↗