Biomedical subjects

Jose A Luchsinger

Publications and source records attributed to Jose A Luchsinger.

14 recordsLinked to original sources

PubMed2024

Urinary Metal Levels, Cognitive Test Performance, and Dementia in the Multi-Ethnic Study of Atherosclerosis.

IMPORTANCE: Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited. OBJECTIVE: To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4). DESIGN, SETTING, AND PARTICIPANTS: The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018. A total of 6303 MESA participants were included. Data analysis was performed from October 12, 2023, to June 13, 2024. EXPOSURE: Urine samples were collected at baseline (2000-2002), and arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc levels were measured in 2020-2022. MAIN OUTCOMES AND MEASURES: Digit Symbol Coding (DSC) (n = 3819) (possible score range, 0-133), Cognitive Abilities Screening Instrument (CASI) (n = 3918) (possible score range, 0-100), and Digit Span (DS) (n = 4176) (possible score range, 0-30) cognitive tests were administered in 2010-2012; higher scores of each test indicate increasing levels of positive response. RESULTS: A total of 6303 participants were followed up for dementia diagnosis through 2018. The median age at baseline was 60 (IQR, 53-70) years, and 3303 participants (52.4%) were female. The median cognitive scores were 51 (IQR, 38-64) for DSC, 90 (IQR, 84-95) for CASI, and 15 (IQR, 12-18) for DS. There were 559 cases of dementia through the follow-up period. Inverse associations with DSC were identified: mean differences in z scores per IQR increase in metal levels were -0.03 (95% CI, -0.07 to 0.00) for arsenic, -0.05 (95% CI, -0.09 to -0.004) for cobalt, -0.05 (95% CI, -0.07 to -0.02) for copper, -0.04 (95% CI, -0.08 to -0.001) for uranium, and -0.03 (95% CI, -0.06 to -0.01) for zinc. Among 1058 APOE4 carriers, manganese was also inversely associated with DSC. The joint mean difference of DSC comparing percentile 95th with the 25th of the 9-metal mixture was -0.30 (95% CI, -0.47 to -0.14) for APOE4 carriers and -0.10 (95% CI, -0.19 to -0.01) for noncarriers. Arsenic, cadmium, cobalt, copper, tungsten, uranium, and zinc were individually associated with dementia, with hazard ratios per IQR of metal ranging from 1.15 (95% CI, 1.03-1.29) for tungsten to 1.46 (95% CI, 1.06-2.02) for uranium. The joint hazard ratio of dementia comparing percentiles 95th with the 25th of the 9-metal mixture was 1.71 (95% CI, 1.24-3.89), with no significant difference by APOE4 status. CONCLUSIONS AND RELEVANCE: In this study, participants with higher concentrations of metals in their urine, compared with those with lower concentrations, had worse performance on cognitive tests and greater likelihood of developing dementia. The findings of this multicenter multiethnic cohort study might inform screening and potential interventions for prevention of dementia based on individuals' metal exposure levels and genetic profiles.

Humans↗

PubMed2006

Mediterranean diet, Alzheimer disease, and vascular mediation.

OBJECTIVES: To examine the association between the Mediterranean diet (MeDi) and Alzheimer disease (AD) in a different AD population and to investigate possible mediation by vascular pathways. Design, Setting, Patients, and MAIN OUTCOME MEASURES: A case-control study nested within a community-based cohort in New York, NY. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of AD status (194 patients with AD vs 1790 nondemented subjects) in logistic regression models that were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, medical comorbidity index, and body mass index (calculated as weight in kilograms divided by height in meters squared). We investigated whether there was attenuation of the association between MeDi and AD when vascular variables (stroke, diabetes mellitus, hypertension, heart disease, lipid levels) were simultaneously introduced in the models (which would constitute evidence of mediation). RESULTS: Higher adherence to the MeDi was associated with lower risk for AD (odds ratio, 0.76; 95% confidence interval, 0.67-0.87; P<.001). Compared with subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had an odds ratio of 0.47 (95% confidence interval, 0.29-0.76) and those at the highest tertile an odds ratio of 0.32 (95% confidence interval, 0.17-0.59) for AD (P for trend <.001). Introduction of the vascular variables in the model did not change the magnitude of the association. CONCLUSIONS: We note once more that higher adherence to the MeDi is associated with a reduced risk for AD. The association does not seem to be mediated by vascular comorbidity. This could be the result of either other biological mechanisms (oxidative or inflammatory) being implicated or measurement error of the vascular variables.

Age Factors↗

PubMed2006

A work in progress: the metabolic syndrome.

Metabolic syndrome refers to a constellation of risk factors for cardiovascular disease. They include elevated plasma glucose concentrations, dyslipidemia, hypertension, and abdominal obesity. These conditions typically occur during middle age or later in life. Although there is no clear consensus on the diagnosis of metabolic syndrome, it is a potentially important entity to recognize and manage once traditional cardiovascular risk factors, such as smoking, hypertension, dyslipidemia, and diabetes, have been treated individually. This Perspective summarizes our current knowledge of the metabolic syndrome. Lifestyle change, including diet and exercise, is probably the best available option for treating the metabolic syndrome. However, rigorous lifestyle interventions are difficult to implement outside of a clinical trial setting, especially among elderly patients.

Adult↗

PubMed2006

Stroke and memory performance in elderly persons without dementia.

BACKGROUND: There are conflicting data showing that stroke is associated with a higher risk of dementia and a more severe decline in persons with cognitive impairment. However, it remains unclear if cerebrovascular disease is directly related to cognitive decline in the absence of cognitive impairment or dementia. OBJECTIVE: To examine the association between stroke and changes in cognitive function over time in elderly persons without dementia at baseline. DESIGN: The results of neuropsychological tests from several intervals over a 5-year period were clustered into domains of memory, abstract/visuospatial, and language in 1271 elderly persons without dementia or cognitive decline. Stroke was related to the slope of performance in each cognitive domain using generalized estimating equations. RESULTS: Memory performance declined over time, while abstract/visuospatial and language performance remained stable during the study period. Stroke was associated with a more rapid decline in memory performance, while there was no association between stroke and decline in abstract/visuospatial or language performance. The association between stroke and decline in memory performance was strongest for men and for persons without an APOEepsilon4 allele. A significant association between stroke and decline in abstract/visuospatial performance was also observed for persons without the APOEepsilon4 allele. CONCLUSION: A history of stroke is related to a progressive decline in memory and abstract/visuospatial performance, especially among men and those without an APOEepsilon4 allele.

Aged↗

PubMed2006

History of vascular disease and mild parkinsonian signs in community-dwelling elderly individuals.

BACKGROUND: Mild parkinsonian signs (MPS) are commonly found during the clinical examination of older people. These signs could reflect the accumulation of vascular pathological changes in the brain. If the etiology were vascular, one could hypothesize that individuals with MPS would be more likely to have systemic vascular disease than would their counterparts without these signs. OBJECTIVES: To examine whether MPS are associated with a history of vascular disease and whether certain MPS (rigidity, changes in axial function) are more strongly associated with a history of vascular disease than are other MPS (tremor). METHODS: Evaluation of older people without dementia in Washington Heights-Inwood, northern Manhattan, NY. The presence of vascular diseases was assessed with a structured health interview. RESULTS: Mild parkinsonian signs were present in 375 (16.4%) of 2286 participants without dementia. Diabetes mellitus, heart disease, peripheral vascular disease, and stroke were more prevalent in participants with MPS than without MPS, whereas nonvascular diseases (cancer, thyroid disease) were not. In a logistic regression analysis that adjusted for age, sex, education, and depressive symptoms, the number of vascular diseases was associated with MPS (odds ratio, 1.31 [95% confidence interval, 1.18-1.46]; P<.001). The combination of diabetes mellitus and heart disease increased the odds of MPS by 70% and the combination of these with stroke increased the odds by 332%. CONCLUSIONS: The presence of MPS in elderly individuals might reflect, in part, the accumulation of vascular pathological changes in the basal ganglia or white matter regions caused by preventable vascular diseases. Prospective and pathological studies are needed to further explore this finding.

Aged↗

PubMed2006

Mediterranean diet and risk for Alzheimer's disease.

OBJECTIVE: Previous research in Alzheimer's disease (AD) has focused on individual dietary components. There is converging evidence that composite dietary patterns such as the Mediterranean diet (MeDi) is related to lower risk for cardiovascular disease, several forms of cancer, and overall mortality. We sought to investigate the association between MeDi and risk for AD. METHODS: A total of 2,258 community-based nondemented individuals in New York were prospectively evaluated every 1.5 years. Adherence to the MeDi (zero- to nine-point scale with higher scores indicating higher adherence) was the main predictor in models that were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, medical comorbidity index, and body mass index. RESULTS: There were 262 incident AD cases during the course of 4 (+/-3.0; range, 0.2-13.9) years of follow-up. Higher adherence to the MeDi was associated with lower risk for AD (hazard ratio, 0.91; 95% confidence interval, 0.83-0.98; p=0.015). Compared with subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had a hazard ratio of 0.85 (95% confidence interval, 0.63-1.16) and those at the highest tertile had a hazard ratio of 0.60 (95% confidence interval, 0.42-0.87) for AD (p for trend=0.007). INTERPRETATION: We conclude that higher adherence to the MeDi is associated with a reduction in risk for AD.

Aged↗

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

Semiquantitative study of current coffee, caffeine, and ethanol intake in essential tremor cases and controls.

There are several reasons to study caffeine, coffee, and ethanol intake in essential tremor (ET) patients. ET patients also might modify their use of these beverages because of their effects on tremor. Intake of caffeine, coffee, and ethanol has not been quantified in a group of ET patients. Our objective is to use a semiquantitative food frequency questionnaire to compare current daily intake of coffee, caffeine, and ethanol in ET patients and controls. A total of 130 ET cases were patients at the Neurological Institute of New York, and 175 controls were ascertained by random digit dialing. Caffeine (in milligrams) and ethanol (in grams) intake were calculated from a semiquantitative food-frequency questionnaire. Mean daily caffeine intake in patients was 138.4 versus 246.6 mg in controls; medians were 101.1 versus 175.5 mg (P < 0.001). Mean daily ethanol intake in patients was 8.2 versus 6.2 gm in controls; medians were 2.4 versus 1.9 gm (P = 0.89). Cases drank less coffee than controls, but drank similar amounts of tea, soft drinks, fruit juices, and milk. Daily caffeine intake was not correlated with tremor severity or duration. ET patients consumed less caffeine than did controls, which is likely to be a dietary modification in response to tremor. The observation that caffeine consumption was not correlated with tremor severity raises the additional possibility that lower caffeine consumption in ET patients may not exclusively be a response to tremor. A prospective study is needed to explore whether decreased caffeine consumption is a risk factor for ET.

Aged↗

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.

Aged↗

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

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

Antihypertensive medication class and pulse pressure in the elderly: analysis based on the third National Health and Nutrition Examination Survey.

BACKGROUND: Widened pulse pressure is an independent predictor of cardiovascular outcomes in older persons. The purpose of this study was to examine the associations between antihypertensive medication class and the magnitude of pulse pressure among persons receiving treatment for hypertension in the third National Health and Nutrition Examination Survey. METHODS: We analyzed cross-sectional data on 1429 subjects aged 60 years or older who reported receiving one or two hypertensive drugs from the following medication classes: beta-blockers, diuretics, calcium channel blockers, or angiotensin-converting enzyme inhibitors. The sample represented about 9 million people in the noninstitutionalized U.S. population. RESULTS: For the sample as a whole, no significant pulse pressure difference was found for any medication class when compared with the referent beta-blocker group after adjustment for covariates, including mean arterial pressure. In a subgroup analysis stratified by median age, mean pulse pressure was lower in subjects older than 72 years who used diuretics alone (difference = -7 mm Hg, P <0.05) or in combination with beta-blockers (difference = -7 mm Hg, P <0.01) than in those who used beta-blockers alone. CONCLUSION: Older hypertensive subjects who used diuretics alone or in combination with beta-blockers had lower mean pulse pressure as compared with those using beta-blockers alone. These findings lend support to recommendations for use of diuretics in older hypertensive patients.

Adrenergic beta-Antagonists↗

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↗

PubMed2002

The effect of body mass index on complications from cardiac surgery in the oldest old.

OBJECTIVES: Overweight (body mass index (BMI)>25) and obesity (BMI>30) are associated with adverse outcomes in the general population. In older people, an increased risk of adverse events was observed in leaner and overweight older subjects. We evaluated the association between BMI and cardiac surgery complications in subjects aged 75 and older. DESIGN: Retrospective review of complication rates compiled as part of the New York State Department of Health Adult Cardiac Surgery Report. SETTING: Academic tertiary care medical center. PARTICIPANTS: One thousand four hundred forty-eight subjects aged 75 and older who underwent cardiac surgery in an academic hospital between 1991 and 1999. MEASUREMENTS: Subjects were divided into tertiles based on their BMI. Logistic regression was used in multivariate analyses examining the association between tertiles of BMI (<23, 23-26,>26) and complications from cardiac surgery, adjusting for age and gender or using a full model adjusting for history of diabetes mellitus, hypertension, myocardial infarction (MI), congestive heart failure, smoking, chronic obstructive pulmonary disease, peripheral vascular disease, renal disease, surgical priority, age, and gender. RESULTS: Mean age was 79 (range 75-94); 58% of the subjects were male. The incidence of any postoperative complication, respiratory failure, or death was U-shaped, with higher incidence in the first tertile of BMI, followed by the last tertile and then the middle tertile. Subjects in the lowest tertile of BMI in the full model had a higher adjusted risk of stroke (odds ratio (OR) = 1.58, 95% confidence interval (CI) = 0.96-2.59), bleeding (OR = 1.71, 95% CI = 0.79-3.67), respiratory failure (OR = 1.65, 95%CI = 0.95-2.87), cardiovascular complications (stroke, MI, arrhythmia) (OR = 1.59, 95% CI = 0.93-2.73), and all complications (OR = 1.45, 95% CI = 1.05-2.00) than subjects in the middle tertile. The risk of most complications in subjects in the highest tertile of BMI was similar to that of subjects in the middle tertile except for wound infections (OR = 3.51, 95% CI = 0.92-13.33). The risk of death was higher in subjects in the lower tertile of BMI (OR = 1.97, 95% CI = 1.12-3.44) than in subjects in the middle tertile. The association between BMI and adverse cardiac surgical outcomes was stronger in men than women and decreased with advancing age. CONCLUSIONS: In the geriatric population, subjects with lower BMI have a higher risk of complications and death from cardiovascular surgery than subjects with higher BMI. An increased BMI does not increase the risk of complications from cardiovascular surgery, with the exception of wound infections.

Aged↗