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Richard Mayeux

Publications and source records attributed to Richard Mayeux.

At least 55 records · Page 3Linked to original sources
PubMed2004

Preservation of cognitive and functional ability as markers of longevity.

Longevity is a complex biological process for which the phenotypes have not been established. Preservation of cognitive and physical function may be important and preservation of these functions is, in part, inherited. We investigated the relation between rate of change in cognitive and functional abilities in probands and risk of death in their siblings. Probands were classified as showing no decline, slow, medium, or rapid rate of decline, based on the slope of change in cognitive and physical/functional factors over three or more assessments. Siblings of probands who did not decline on measures of memory, visuospatial/cognitive function or ADL skills were approximately half as likely to die as siblings of probands who had the most rapid decline. The reduction in risk of death in siblings of probands who did not decline in was primarily observed among siblings of probands who were older than 75 years, suggesting that genetic influences on life span may be greater at older ages. There was no association between probands' rate of change in language, IADL skills, upper or lower extremity mobility and risk of death in siblings. The results of the present study identify phenotypes associated with preserved cognitive and functional abilities which may serve as markers for longevity.

Activities of Daily Living↗
PubMed2004

Elevated sex-hormone binding globulin in elderly women with Alzheimer's disease.

BACKGROUND: Hormone levels change significantly with increasing age. These changes may be related to, or be associated with, the emergence of age-related diseases, such as Alzheimer's disease (AD). METHODS: Five hundred and seventy-six women over the age of 65 were studied from the Washington Heights-Inwood Columbia Aging Project (WHICAP). These women were selected from a group of healthy Medicare beneficiaries that were aged 65 and older living in the geographically defined area of northern Manhattan in New York City. Serum levels of estrone (E1), estradiol (E2), total testosterone (TT), dehydroepiandosterone (DHEA), luteinizing hormone (LH), follicle stimulating hormone (FSH), and sex-hormone binding globulin (SHBG) were measured. RESULTS: Significant differences were found between patients with AD and controls only in the level of SHBG, which was 20% higher in patients compared to controls (68.5nmol/l versus 54.7nmol/l, P<0.001). We also estimated levels of total E2 because after menopause, E2 is largely derived from E1. AD patients had significantly lower levels of estimated E2 (AD 0.46 versus controls 0.49, P<0.01). Differences remained significant after adjusting for age, ethnic group, education, and body mass index (BMI). CONCLUSIONS: A marked increase in SHBG levels was found in AD patients. SHBG normally responds to circulating testosterone and estrogen, therefore, elevated SHBG suggests an abnormal increase in its production and regulation. Further work is needed to clarify the cause and consequences of this observation.

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PubMed2004

Obesity enhances verbal memory in postmenopausal women with Down syndrome.

Several lines of evidence suggest that the loss of estrogen after menopause may play a role in cognitive declines associated with Alzheimer's disease (AD). In postmenopausal women, the principal source of estrogen is estrone, which is influenced by body mass index (BMI). Increased BMI in postmenopausal women is associated with higher levels of serum estradiol and estrone. We hypothesized that obesity could have a beneficial effect on cognition with advancing age. We compared the performance of healthy nondemented obese and non-obese women with Down syndrome (DS) on a broad spectrum of cognitive tests. Estrone levels were 66.9% higher in obese than in non-obese postmenopausal women, and 136% higher in obese than in non-obese premenopausal women. Obese postmenopausal women performed significantly better than non-obese women on measures of verbal memory and on an omnibus test of neuropsychological function, but did not differ significantly in verbal fluency, language, praxis or visuospatial functioning. Among premenopausal women, there was no difference in cognitive function between obese and non-obese women. Our results support the hypothesis that higher endogenous estrogen levels after menopause are associated with better performance on verbal memory.

Adult↗
PubMed2004

Dietary factors and Alzheimer's disease.

Alzheimer's disease (AD) is increasing in prevalence, and environmental risk factors have not been identified with certainty. There is evidence that oxidative stress, homocysteine-related vitamins, fats, and alcohol have a role in the pathogenesis of AD. Few large epidemiological studies have explored the associations between nutrients and AD, and there has been only one trial of vitamin E in the prevention of AD. Some studies suggest that high intake of vitamins C, E, B6, and B12, and folate, unsaturated fatty acids, and fish are related to a low risk of AD, but reports are inconsistent. Modest to moderate alcohol intake, particularly wine, may be related to a low risk of AD. Available data do not permit definitive conclusions regarding diet and AD or specific recommendations on diet modification for the prevention of AD.

Alzheimer Disease↗
PubMed2004

Alcohol intake and risk of dementia.

OBJECTIVES: To examine the association between intake of alcoholic beverages and risk of Alzheimer's disease (AD) and dementia associated with stroke (DAS) in a cohort of elderly persons from New York City. DESIGN: Cohort study. SETTING: The Washington Heights Inwood-Columbia Aging Project. PARTICIPANTS: Nine hundred eighty community-dwelling individuals aged 65 and older without dementia at baseline and with data on alcohol intake recruited between 1991 and 1996 and followed annually. MEASUREMENTS: Intake of alcohol was measured using a semiquantitative food frequency questionnaire at baseline. Subjects were followed annually, and incident dementia was diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria and classified as AD or DAS. RESULTS: After 4 years of follow-up, 260 individuals developed dementia (199 AD, 61 DAS). After adjusting for age, sex, apolipoprotein E (APOE)-epsilon 4 status, education, and other alcoholic beverages, only intake of up to three daily servings of wine was associated with a lower risk of AD (hazard ratio=0.55, 95% confidence interval=0.34-0.89). Intake of liquor, beer, and total alcohol was not associated with a lower risk of AD. Stratified analyses by the APOE-epsilon 4 allele revealed that the association between wine consumption and lower risk of AD was confined to individuals without the APOE-epsilon 4 allele. CONCLUSIONS: Consumption of up to three servings of wine daily is associated with a lower risk of AD in elderly individuals without the APOE epsilon-4 allele.

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PubMed2004

A comparison of family history of psychiatric disorders among patients with early- and late-onset Alzheimer's disease.

OBJECTIVE: Both early-onset Alzheimer's Disease (EOAD) and late-onset Alzheimer's Disease (LOAD) present with cognitive and psychiatric features. Some studies suggest that EOAD patients are more likely than LOAD patients to have psychiatric symptoms. If this is true, relatives of EOAD patients with a similar clinical presentation may be more likely to be misclassified as having a primary noncognitive psychiatric disorder rather than a dementing disorder. Family history studies may underestimate familial aggregation of EOAD. METHODS: The authors compared the presence of psychiatric symptoms in parents and siblings of 131 EOAD patients (diagnosed at or before age 60), with the parents and siblings of 131 LOAD patients (diagnosed at or after age 65). Early onset Alzheimer's Disease and LOAD patients were matched for diagnosis (probable versus possible AD), gender, and ethnic group. Logistic regression analysis was performed on the outcome variable of patient group (EOAD, LOAD) with family history of psychiatric symptoms as the risk factor, adjusting for family size and patient's education. RESULTS: There was a nearly two and one-half-fold increase in family history of psychiatric symptoms among EOAD patients when compared with LOAD patients (RR = 2.4; 95% C.I. 1.2-4.7). CONCLUSIONS: The authors found preliminary evidence of a higher prevalence of a history of psychiatric symptoms among relatives of EOAD patients when compared to LOAD patients. This may be due to differential misclassification of AD, a syndromic disorder with both noncognitive psychiatric and cognitive deficits in relatives of EOAD patients. Alternatively, shared genetic or other familial etiologies may underlie subtypes of EOAD and some psychiatric disorders.

Age of Onset↗
PubMed2004

Biomarkers: potential uses and limitations.

Biomarkers provide a dynamic and powerful approach to understanding the spectrum of neurological disease with applications in observational and analytic epidemiology, randomized clinical trials, screening and diagnosis and prognosis. Defined as alterations in the constituents of tissues or body fluids, these markers offer the means for homogeneous classification of a disease and risk factors, and the can extend our base information about the underlying pathogenesis of disease. Biomarkers can also reflect the entire spectrum of disease from the earliest manifestations to the terminal stages. This brief review describes the major uses of biomarkers in clinical investigation. Careful assessment of the validity of biomarkers is required with respect to the stage of disease. Causes of variability in the measurement of biomarkers range from the individual to the laboratory. Issues that affect the analysis of biomarkers are discussed along with recommendations on how to deal with bias and confounding.

Biomarkers↗
PubMed2003

The genetics of adult-onset neuropsychiatric disease: complexities and conundra?

Genetic factors play a major role in the etiology of adult-onset neurodegenerative and neuropsychiatric disorders. Several highly penetrant genes have been cloned for rare, autosomal-dominant, early-onset forms of neurodegenerative diseases. These genes have provided important insights into the mechanisms of these diseases (often altering neuronal protein processing). However, the genes associated with inherited susceptibility to late-onset neurodegenerative diseases, schizophrenia, and bipolar disorder appear to have smaller effects and are likely to interact with each other (and with nongenetic factors) to modulate susceptibility and/or disease phenotype. Several strategies have recently been applied to address this complexity, leading to the identification of a number of candidate susceptibility loci/genes.

Adult↗
PubMed2003

The Saitohin 'Q7R' polymorphism and tau haplotype in multi-ethnic Alzheimer disease and Parkinson's disease cohorts.

In a multi-ethnic cohort we analyzed the Saitohin (STH) gene 'Q7R' polymorphism in 200 late-onset Alzheimer's disease cases (LOAD), 60 Parkinson's disease cases with dementia (PDD), 84 Parkinson's disease cases without dementia and 458 controls. We found no significant differences in genotype or allele frequencies when LOAD or PD cases were compared to controls. Ethnic differences in STH genotype frequencies for cases and controls were observed and these were statistically significant (cases n=344, P<0.03; controls n=458, P<0.001). We also observed a trend in non-Hispanic white PDD cases with the STH 'QQ' (Tau H1/H1) genotype increased (76%) compared to PD cases without dementia (61.7%) and controls (56.6%); however, this difference was not statistically significant (PDD vs. controls OR 2.1; 95% CI: 0.8-5.8, P=0.2).

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PubMed2003

Parkinsonian signs in older people: prevalence and associations with smoking and coffee.

BACKGROUND: Cigarette smoking and coffee consumption may reduce the risk of PD. Parkinsonian signs (tremor, rigidity, bradykinesia) occur in 30 to 40% of the elderly. OBJECTIVE: To determine whether there was an association between cigarette smoking, coffee consumption, and parkinsonian signs in a community population of older people. METHODS: Data on smoking were collected and a neurologic examination performed on 1,339 residents > or = 65 years of age in the Washington Heights-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. Coffee consumption was assessed with a semiquantitative food-frequency questionnaire, and caffeine consumption was determined. Analyses were cross-sectional. RESULTS: Mean age was 76.6 years. Parkinsonian signs were present in 537 (40.1%). The odds for presence of parkinsonian signs was lower in smokers than nonsmokers (odds ratio [OR] = 0.58, 95% CI = 0.47 to 0.73). Smokers had a lower mean parkinsonian sign score than nonsmokers (p < 0.001). Coffee drinking and caffeine consumption were not associated with the presence of parkinsonian signs. The odds for presence of parkinsonian signs remained lower in smokers (OR = 0.75, 95% CI = 0.57 to 0.99) after adjusting for age, gender, ethnicity, years of education, adjusted daily caffeine consumption, and dementia. CONCLUSION: The reduced risk of parkinsonian signs in cigarette smokers could reflect a protective effect of smoking on age-related parkinsonian signs in the elderly or an aversion to smoking in elderly persons with mild parkinsonism.

Aged↗
PubMed2003

Epidemiology of neurodegeneration.

Alzheimer's disease, Parkinson's disease, and motor neuron disease share a propensity to occur with increasing age and as either a sporadic or a familial disorder. A number of behavioral and environmental risk factors have been proposed for each disorder, but most associations lack consistency and specificity. Over the last decade the remarkable frequency of these disorders has become apparent, and the identification of mutations in genes has provided the means to understand their pathogenesis. Better and more accurate means to characterize and diagnose these diseases has greatly facilitated analytic epidemiology. The analysis of behavioral and genetic factors that may lower disease risk has led to clinical trials that are either in progress or being planned with the aim of preventing these disorders.

Alzheimer Disease↗
PubMed2003

Stroke and the risk of Alzheimer disease.

BACKGROUND: Alzheimer disease (AD) and stroke are common in elderly individuals, but the relation between these 2 disorders remains uncertain. OBJECTIVE: To investigate the association between a clinical history of stroke and subsequent risk of AD. DESIGN: A cohort of 1766 Medicare recipients without dementia participated in a longitudinal follow-up study from 1992 through 1999 in upper Manhattan, New York, NY. History of stroke and presence of cardiovascular risk factors were ascertained at the onset of the study. Incidence rates for AD among those with and without stroke were calculated; proportional hazards ratios were computed using age at onset of the disease as the time-to-event variable. RESULTS: The annual incidence for AD was 5.2% among individuals with stroke vs 4% for those without stroke. The hazards ratio for AD among those with a history of stroke was 1.6 (95% confidence interval, 1.0-2.4) compared with those without stroke. Of the vascular risk factors, hypertension, diabetes, and heart disease, only diabetes related to risk of AD in the absence of stroke. Stroke remained weakly associated with AD in the absence of these factors, but risk significantly increased with the additional factors of hypertension (relative risk, 2.3; 95% confidence interval, 1.4-3.6), diabetes (relative risk, 4.6; 95% confidence interval, 2.2-9.5), or heart disease (relative risk, 2.0; 95% confidence interval, 1.2-3.2). CONCLUSIONS: Stroke is associated with AD among elderly individuals. The relation is strongest in the presence of known vascular risk factors. The observed association between stroke and AD might relate to an underlying systemic vascular disease process, or alternatively, to the additive effects of stroke and AD pathologic features, leading to an earlier age at onset of disease.

Aged↗
PubMed2003

Antioxidant vitamin intake and risk of Alzheimer disease.

BACKGROUND: The generation of oxygen free radicals is involved in the pathogenesis of Alzheimer disease (AD). OBJECTIVE: To determine whether the intake of antioxidant vitamins decreases the risk of AD. METHODS: We investigated the relationship between AD and the intake of carotenes, vitamin C, and vitamin E in 980 elderly subjects in the Washington Heights-Inwood Columbia Aging Project who were free of dementia at baseline and were followed for a mean time of 4 years. Semiquantitative food frequency questionnaires were administered between baseline and the first follow-up visit. Cox proportional hazards regression models were conducted with quartiles of each vitamin intake as the exposure of interest and incident AD as the outcome, adjusted for age, level of education, sex, APOE epsilon4 status, ethnicity, and smoking. RESULTS: There were 242 incident cases of AD in 4,023 person-years of follow-up (6 per 100 person-years). Intake of carotenes and vitamin C, or vitamin E in supplemental or dietary (nonsupplemental) form or in both forms, was not related to a decreased risk of AD. Trend tests for the association between quartiles of total intake of vitamins C and E also were not significant. CONCLUSION: Neither dietary, supplemental, nor total intake of carotenes and vitamins C and E was associated with a decreased risk of AD in this study.

Aged↗
PubMed2003

Onset of dementia is associated with age at menopause in women with Down's syndrome.

Women with Down's syndrome experience early onset of both menopause and Alzheimer's disease. This timing provides an opportunity to examine the influence of endogenous estrogen deficiency, indicated by age at menopause, on risk of Alzheimer's disease. A community-based sample of 163 postmenopausal women with Down's syndrome, 40 to 60 years of age, was ascertained through the New York State Developmental Disability service system. Information from cognitive assessments, medical record review, neurological evaluation, and caregiver interviews was used to establish ages for onset of menopause and dementia. We used survival and multivariate regression analyses to determine the relation of age at menopause to age at onset of Alzheimer's disease, adjusting for age, level of mental retardation, body mass index, and history of hypothyroidism or depression. Women with early onset of menopause (46 years or younger) had earlier onset and increased risk of Alzheimer's disease (AD) compared with women with onset of menopause after 46 years (rate ratio, 2.7; 95% confidence interval [CI], 1.2-5.9). Demented women had higher mean serum sex hormone binding globulin levels than nondemented women (86.4 vs 56.6 nmol/L, p = 0.02), but similar levels of total estradiol, suggesting that bioavailable estradiol, rather than total estradiol, is associated with dementia. Our findings support the hypothesis that reductions in estrogens after menopause contribute to the cascade of pathological processes leading to AD.

Adult↗
PubMed2002

Comparison of modifiable determinants of lipids and lipoprotein levels among African-Americans, Hispanics, and Non-Hispanic Caucasians > or =65 years of age living in New York City.

Information on determinants of plasma lipids and lipoproteins and how these factors would differ among race/ethnic groups in elderly populations is scarce. We studied cross-sectionally the distribution and predictors of lipids and lipoproteins in 1,118 free-living elderly subjects (> or =65 years of age), in a multiethnic urban community (22% non-Hispanic Caucasian, 34% African-American, and 44% Hispanic). Mean levels of total cholesterol, total/high-density lipoprotein (HDL) cholesterol ratio, and triglycerides decreased with increasing age (p <0.001). Low-density lipoprotein cholesterol and total cholesterol were lower among men, whereas women had higher levels of HDL cholesterol (p <0.001). Hispanics had lower low-density lipoprotein cholesterol, total cholesterol, and HDL cholesterol levels, whereas African-Americans had a lower total/HDL cholesterol ratio and triglyceride levels along with higher HDL cholesterol levels (p <0.001). Diabetes was more prevalent among Hispanics and African-Americans (p = 0.002), and body mass index was higher in African-Americans (p = 0.009). Hispanics were less likely to drink alcohol (p <0.0001), but more likely to drink larger amounts of coffee (p <0.0001). A greater proportion of African-Americans were active smokers (p <0.001). In multivariate regression models, body mass index was a significant independent predictor of total cholesterol (beta = 0.74, p <0.001). Waist circumference predicted lower HDL cholesterol levels (0.57 mg/dl lower per inch, p <0.001) and a higher total/HDL cholesterol ratio (beta = 0.05, p <0.001). Alcohol intake (>2 g/day) predicted higher HDL cholesterol (beta = 6.20, p <0.001). Diabetic status predicted lower HDL cholesterol (beta = -2.47, p <0.05), higher total/HDL cholesterol ratio (beta = 0.35, p <0.001), and triglycerides (beta = 37.10, p <0.001). Physical activity, coffee intake, and a calorie-adjusted atherogenicity index did not show independent predictive value. These findings indicate that obesity, alcohol intake, and diabetes mellitus are potentially modifiable independent determinants of lipids and lipoprotein levels in an elderly multiethnic population.

Black or African American↗
PubMed2002

Familial Alzheimer disease among Caribbean Hispanics: a reexamination of its association with APOE.

OBJECTIVES: To reexamine the association between the apolipoprotein E epsilon4 allele (APOE epsilon4) and familial Alzheimer disease (AD), and to search for novel genes that may be associated with susceptibility in Caribbean Hispanic families with a history of AD. METHODS: Families were identified in Caribbean Hispanic communities in the greater New York City area, the Dominican Republic, and Puerto Rico. Each family in the study cohort included at least 2 living relatives with a history of dementia. All family members underwent neuropsychological testing and medical and neurological examinations to establish the presence or absence of dementia and to specify the type of dementia. RESULTS: Over a 2(1/2)-year period, 203 families were identified. Of these, 19 families had at least 1 family member with onset of dementia before age 55 years, with 8 of the 19 families showing an association with a previously unreported presenilin mutation. Multiple cases of AD were identified in 29 families. Overall, there were 236 affected sibling pairs with AD available for analysis. The average age at onset was 74 years. The presence of APOE epsilon4 was strongly associated with AD. CONCLUSIONS: Both early-onset and late-onset familial AD occur in Caribbean Hispanics. In contrast to sporadic AD, late-onset familial AD among Caribbean Hispanics is strongly associated with APOE epsilon4. Future attempts to identify additional susceptibility genes should consider the effects of APOE epsilon4.

Aged↗
PubMed2002

Caloric intake and the risk of Alzheimer disease.

BACKGROUND: Diet may play a role in Alzheimer disease (AD). OBJECTIVE: To examine the association between caloric intake and AD. METHODS: Elderly individuals free of dementia at baseline (N = 980) were followed for a mean of 4 years. Daily intake of calories, carbohydrates, fats, and protein were recalled using a semiquantitative food frequency questionnaire administered between the baseline and first follow-up visits. Proportional hazards models were used to examine the associations of quartiles of intake and incident AD, adjusting for confounders. RESULTS: There were 242 incident cases of AD during 4023 years of follow-up (6 cases per 100 person-years). Compared with individuals in the lowest quartile of caloric intake, those in the highest quartile had an increased risk of AD (hazard ratio, 1.5; 95% confidence interval [CI], 1.0-2.2). Among individuals with the apolipoprotein E epsilon4 allele, the hazard ratios of AD for the highest quartiles of calorie and fat intake were 2.3 (95% CI, 1.1-4.7) and 2.3 (95% CI, 1.1-4.9), respectively, compared with the lowest quartiles. The hazard ratios of AD for the highest quartiles of calorie and fat intake compared with the lowest quartiles in individuals without the apolipoprotein E epsilon4 allele were close to 1 and were not statistically significant (P =.83 and P =.61, respectively). CONCLUSION: Higher intake of calories and fats may be associated with higher risk of AD in individuals carrying the apolipoprotein E epsilon4 allele.

Aged↗