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Biomedical subjects

L J Launer

Publications and source records attributed to L J Launer.

At least 73 records · Page 4Linked to original sources

Association between apolipoprotein E epsilon4 and the rate of cognitive decline in community-dwelling elderly individuals with and without dementia.

OBJECTIVE: To determine whether the apolipoprotein E epsilon4 allele (apoE epsilon4) is associated with cognitive decline in individuals with and without dementia, we conducted a 4-year longitudinal study of subjects with a range of cognitive function. SETTING: At baseline, respondents (n=511) were randomly selected according to age and Mini-Mental State Examination score from a community-based study of dementia among noninstitutionalized persons aged 65 to 84 years. Respondents were examined at baseline and followed up in 3 annual visits. At baseline, subjects were classified as having normal cognitive function, minimal dementia, or dementia, according to criteria from the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) and the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Of the 511 respondents at baseline, 405 who were examined at least 2 times are included in this analysis. MAIN OUTCOME MEASURES: Cognitive decline was determined by a slope estimating yearly change in score on the neuropsychological test, the CAMCOG (the cognitive section of the CAMDEX), and its sub-scales of memory and nonmemory functions. RESULTS: Among the subjects who had normal cognitive function at baseline, apoE epsilon4 carriers showed a significantly greater decline (P<.001) in score on the CAMCOG compared with noncarriers. Differences in decline on the memory and nonmemory subtests were also significant (P<.001). Rates of cognitive decline were not related to apoE epsilon4 status in the groups with minimal dementia and dementia. CONCLUSIONS: In our community-based sample, apoE epsilon4 was associated with the rate of cognitive decline prior to the clinically symptomatic phase of dementia. Knowing the apoE epsilon4 status of those already symptomatic for dementia may not improve knowledge about a patient's prognosis.

Aged↗

Anti-oxidants and cognitive function: a review of clinical and epidemiologic studies.

While the role of diet in heart disease and cancer has received much attention, a possible role for diet in the development of cognitive impairment and dementia is just now being investigated. In this presentation, the putative mechanisms through which anti-oxidants could modulate cellular life in the brain will be briefly discussed. Epidemiologic studies that describe the relation of selected dietary nutrients to cognitive impairment and dementia will be reviewed. In particular, recent results from the analyses of community based follow-up studies, including the Rotterdam Study and the Zutphen Study will be presented. Briefly, these studies provide a mixed picture concerning the relation of anti-oxidants to cognitive impairment or dementia.

Aging↗

Plasma antioxidants and cognitive performance in middle-aged and older adults: results of the Austrian Stroke Prevention Study.

OBJECTIVES: To study the association between cognitive status and plasma concentrations of various antioxidants in middle-aged and older individuals without neuropsychiatric disease. DESIGN: Evaluation of cross-sectional data from a cohort study. SETTING: The Austrian Stroke Prevention Study. PARTICIPANTS: A total of 1769 subjects aged 50 to 75 years, with no history or signs of neuropsychiatric disease, selected randomly from the community register. MEASUREMENTS: The score on the Mattis Dementia Rating Scale (MDRS) was dichotomized according to age-and education-specific lowest quartile cut-off points. Reversed-phase high performance liquid chromatography measurements of the plasma concentrations of lutein/zeaxanthin, cryptoxanthin, canthaxanthin, lycopene, alpha-carotene, beta-carotene, retinol, gamma-tocopherol, alpha-tocopherol, and ascorbate were measured. RESULTS: Individuals with MDRS results below the lowest quartile cut-off point had lower levels of beta-carotene and alpha-tocopherol than their counterparts with test performance above this limit (0.44+/-.33 micromol/L vs 0.51+/-.48 micromol/L, P < .001; and 29.50+/-7.98 micromol/L vs 30.93+/-11.10 micromol/L, P < .001, respectively). Only alphatocopherol remained significantly associated with cognitive functioning when logistic regression analysis was used to adjust for possible confounders including age, sex, month of blood sampling, years of education, smoking, lipid status, and major risk factors for stroke (P = .019). CONCLUSION: These observations are compatible with the view that some dietary antioxidants may protect against cognitive impairment in older people.

Age Factors↗

A prospective study on cortisol, dehydroepiandrosterone sulfate, and cognitive function in the elderly.

The objective of this study was to investigate the relation between the peripheral concentrations of the adrenal steroid hormones cortisol and dehydroepiandrosterone sulfate (DHEAS) and cognitive impairment and decline. A prospective study design was used. The setting was a suburb of Rotterdam, The Netherlands. The study population consisted of a sample of 189 healthy participants from the population-based Rotterdam Study, aged 55-80 yr, who were invited for an additional examination. Follow-up examinations took place 1.9 yr after baseline, on the average. We determined fasting blood levels of DHEAS before dexamethasone administration and of cortisol and corticosteroid-binding globulin before and after the administration of 1 mg dexamethasone overnight. The 30-point Mini-Mental State Examination (MMSE) was used to assess cognition. The associations with cognitive impairment (MMSE score of <26; 6% of the sample) and cognitive decline (drop in MMSE score of >1 point/yr; 24%) were estimated using logistic regression, with adjustment for age, sex, education, and depressive symptoms. An increase of 1 SD in the estimate of free cortisol (SD = 30.3) was associated with cognitive impairment, although not significantly [odds ratio (OR) = 1.5; 95% confidence interval (CI), 0.9-2.4]. A 1 SD increase in the natural logarithm of cortisol after the administration of 1 mg dexamethasone (SD = 0.68) was associated with an OR for cognitive decline of 1.5 (95% CI, 1.0-2.3). A 1 SD increase in DHEAS (SD = 2.10 micromol/L) was inversely, but nonsignificantly, related to cognitive impairment (OR = 0.5; 95% CI, 0.2-1.1) and cognitive decline (OR = 0.6; 95% CI, 0.4-1.1). The ratio of free cortisol over DHEAS was significantly related to cognitive impairment (OR = 1.8; 95% CI, 1.0-3.2). This prospective study among healthy elderly subjects suggested that basal free cortisol levels were positively related to cognitive impairment, and cortisol levels after dexamethasone treatment were related to cognitive decline. There was an inverse, but nonsignificant, association between DHEAS and cognitive impairment and decline.

Aged↗

Cohort study of effect of being overweight and change in weight on risk of coronary heart disease in old age.

OBJECTIVE: To evaluate risk of late life coronary heart disease associated with being overweight in late middle or old age and to assess whether weight change modifies this risk. DESIGN: Longitudinal study of subjects in the epidemiological follow up study of the national health and nutrition examination survey I. SETTING: United States. SUBJECTS: 621 men and 960 women free of coronary heart disease in 1982-84 (mean age 77 years). MAIN OUTCOME MEASURE: Incidence of coronary heart disease. RESULTS: Body mass index of 27 or more in late middle age was associated with increased risk of coronary heart disease in late life (relative risk = 1.7 (95% confidence interval 1.3 to 2.1)) while body mass index of 27 or more in old age was not (1.1 (0.8 to 1.5)). This difference in risk was due largely to weight loss between middle and old age. Exclusion of those with weight loss of 10% or more increased risk associated with heavier weight in old age (1.4 (1.0 to 1.9)). Thinner older people who lost weight and heavier people who had gained weight showed increased risk of coronary heart disease compared with thinner people with stable weight. CONCLUSIONS: Heavier weight in late middle age was a risk factor for coronary heart disease in late life. Heavier weight in old age was associated with an increased risk once those with substantial weight loss were excluded. The contribution of weight to risk of coronary heart disease in older people may be underestimated if weight history is neglected.

Adult↗

Total and sports activity in older men and women: relation with body fat distribution.

Physical activity is reported to be inversely associated with abdominal fat in young and middle-aged populations, which may in part explain its beneficial effect on health. However, it is unclear whether this inverse association exists in older people. The authors investigated the relation of total and sports activity with fat distribution in a population-based sample of 1,163 men and 1,154 women aged 55-85 years, representative of the Dutch elderly population in 1992-1993. Waist and hip circumference and their ratio (WHR) were used as indicators of fat distribution. Physical activity of the previous 2 weeks was obtained by questionnaire. Among men, total physical activity time was negatively associated with waist (98.3 +/- 0.4 cm in the most active quartile vs. 100.5 +/- 0.4 cm in the least active quartile, p = 0.0001 (mean +/- standard error)) and WHR (0.98 +/- 0.00 vs. 0.99 +/- 0.00, p = 0.005) after adjustment for age, education level, body mass index, smoking, and season of the year. This association was not observed among women. Men and women who participated in sports activity had a smaller waist and WHR than those who did not. After adjustment, the time spent on sports activity was negatively associated with waist (p = 0.004 for men and p = 0.07 for women) and WHR (p = 0.03 for men and p = 0.09 for women) in both sexes. No relation between total physical activity time and body fat distribution was observed among respondents who were not participating in any sports activity (p > or = 0.17), suggesting that performance of activities of low/moderate intensity has no effect on body fat distribution. No associations with hip circumference were observed. The results did not change after additional adjustment for chronic illness. The results of this large-scale study show that physical activity, and specifically intensive activity, is negatively associated with abdominal fat in older people.

Adipose Tissue↗

Smoking history in middle age and subsequent cognitive performance in elderly Japanese-American men. The Honolulu-Asia Aging Study.

The associations between cigarette smoking history and later cognitive performance were examined among 3,429 Japanese-American participants of the Honolulu Heart Program (HHP) and its extension, the Honolulu-Asia Aging Study (HAAS). Cognitive performance was measured by the Cognitive Abilities Screening Instrument (CASI), administered as part of HAAS (mean age at HAAS exam (standard deviation (SD)): 77.7 (4.6) years). Information on smoking history was collected during the first and third HHP exams (mean age (SD) at Exam III: 58.6 (4.7) years). Compared with never-smokers, those who had smoked continuously between Exams I-III and those who had quit smoking during that period had significantly lower CASI scores, after adjustment for age, education, Japanese acculturation, and Exam III alcohol intake. In multiple logistic regression controlling for the above covariates, a significantly higher risk of cognitive impairment (CASI score < 82) was associated with continuous smoking (odds ratio (OR) = 1.36, 95% confidence interval (CI) 1.10-1.69) and quitting between Exams I-III (OR = 1.36, 95% CI 1.03-1.80) compared with never smoking. This excess risk of cognitive impairment among continuous smokers and Exam I-III quitters was slightly diminished by further adjustment for body mass index and several vascular covariates. Additional analyses suggested a reduced risk of cognitive impairment among the longer-term quitters. This study suggests a positive association between smoking during middle age and later risk of cognitive impairment.

Aged↗

Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men.

Atherosclerosis and thrombosis may lead to cognitive impairment through cerebral infarcts or white matter hyperintensities. Oxidative stress is now seen as a major contributor to the process of atherogenesis. High intake of polyunsaturated fatty acids, e.g., linoleic acid, or low intake of antioxidants can increase oxidative stress. High intake of n-3 polyunsaturated fatty acids and its main source, fish, may reduce the risk of thrombosis. Little is known, however, about the relation between these dietary factors and cognitive function. The authors investigated this relation with data derived from a cohort of men, aged 69-89 years, who were participants in the Zutphen Elderly Study. The 30-point Mini-Mental State Examination was used to assess cognitive impairment in 1990 (score < or = 25 in 153/476 men, 32%) and cognitive decline from 1990 to 1993 (drop > 2 points in 51/342 men, 15%). Food intake was estimated in 1985 and 1990 by the cross-check dietary history method. High linoleic acid intake was associated with cognitive impairment after adjustment for age, education, cigarette smoking, alcohol consumption, and energy intake (odds ratio (OR) for highest vs. lowest tertile = 1.76, 95% confidence interval (CI) 1.04-3.01). Intake of n-3 polyunsaturated fatty acids was not associated with cognitive impairment, whereas high fish consumption tended to be inversely associated with cognitive impairment (OR = 0.63, 95% CI 0.33-1.21) and cognitive decline (OR = 0.45, 95% CI 0.17-1.16). Intakes of beta-carotene, vitamins C and E, and flavonoids were not inversely associated with cognitive impairment or decline. This study raises the possibility that high linoleic acid intake is positively associated with cognitive impairment and high fish consumption inversely associated with cognitive impairment.

Aged↗

Dietary antioxidants and Parkinson disease. The Rotterdam Study.

OBJECTIVE: To investigate whether high dietary intake of antioxidants decreases the risk of Parkinson disease (PD). SETTING: The community-based Rotterdam Study, the Netherlands. DESIGN: The cross-sectional study formed part of a large community-based study in which all participants were individually screened for parkinsonism and were administered a semiquantitative food frequency questionnaire. The study population consisted of 5342 independently living individuals without dementia between 55 and 95 years of age, including 31 participants with PD (Hoehn-Yahr stages 1-3). RESULTS: The odds ratio for PD was 0.5 (95% confidence interval [CI], 0.2-0.9) per 10-mg daily dietary vitamin E intake, 0.6 (95% CI, 0.3-1.3) per 1-mg beta carotene intake, 0.9 (95% CI, 0.4-1.9) per 100-mg vitamin C intake, and 0.9 (95% CI, 0.7-1.2) per 10-mg flavonoids intake, all adjusted for age, sex, smoking habits, and energy intake. The association with vitamin E intake was dose dependent (P for trend = .03). To assess whether the association was different in participants with more advanced disease, we excluded those with PD who had a Hoehn-Yahr stage of 2.5 or 3. This did not fundamentally alter the results. CONCLUSION: Our data suggest that a high intake of dietary vitamin E may protect against the occurrence of PD.

Aged↗

Dietary fat intake and the risk of incident dementia in the Rotterdam Study.

A high intake of saturated fat and cholesterol and a low intake of polyunsaturated fatty acids have been related to an increased risk of cardiovascular disease. Cardiovascular disease has been associated with dementia. We investigated the association between fat intake and incident dementia among participants, age 55 years or older, from the population-based prospective Rotterdam Study. Food intake of 5,386 nondemented participants was assessed at baseline with a semiquantitative food-frequency questionnaire. At baseline and after an average of 2.1 years of follow-up, we screened for dementia with a three-step protocol that included a clinical examination. The risk of dementia at follow-up (RR [95% CI]) was assessed with logistic regression. After adjustment for age, sex, education, and energy intake, high intakes of the following nutrients were associated with an increased risk of dementia: total fat (RR = 2.4 [1.1-5.2]), saturated fat (RR = 1.9 [0.9-4.0]), and cholesterol (RR = 1.7 [0.9-3.2]). Dementia with a vascular component was most strongly related to total fat and saturated fat. Fish consumption, an important source of n-3 polyunsaturated fatty acids, was inversely related to incident dementia (RR = 0.4 [0.2-0.91), and in particular to Alzheimer's disease (RR = 0.3 [0.1-0.9]). This study suggests that a high saturated fat and cholesterol intake increases the risk of dementia, whereas fish consumption may decrease this risk.

Aged↗

Homocysteine, atherosclerosis and prevalent cardiovascular disease in the elderly: The Rotterdam Study.

OBJECTIVES: Elevated homocysteine increases the risk of vascular disease, in particular amongst younger subjects (< 60 years). Very few studies have been performed amongst older subjects. We evaluated the relation of plasma total homocysteine (tHcy) to atherosclerosis and symptomatic cardiovascular disease amongst older men and women. DESIGN: A cross-sectional study. SETTING: General population. SUBJECTS: A random sample of 630 men and women, participating in the Rotterdam Study, a prospective population-based cohort study amongst 7983 subjects aged 55 years and over residing in the Ommoord district of Rotterdam, the Netherlands. MAIN OUTCOME MEASURES: Carotid atherosclerosis (carotid plaques and common carotid intima-media thickness) assessed by ultrasonography; lower extremity (peripheral) artery atherosclerosis measured by the ratio of the ankle to arm systolic blood pressure; prevalent cardiovascular disease assessed as a history of myocardial infarction or stroke. RESULTS: Subjects, 55-74 years of age, with elevated tHcy levels (+/- 18.6 mumol L-1) had a thicker common carotid intima-media (difference 0.037 mm; 95% CI 0.001, 0.073), a lower ankle-arm index (-0.054; -0.104, -0.004), and an increased risk of cardiovascular disease (odds ratio 3.0; 1.5, 6.1), after adjusting for sex and age. There was no appreciable association of tHcy levels to atherosclerosis and cardiovascular disease in subjects aged 75 years and older. CONCLUSIONS: In subjects aged 55-74 years elevated tHcy is associated with an increased risk of atherosclerosis and cardiovascular disease. The lack of association in those aged > or = 75 years most probably reflect selective mortality.

Aged↗

The diagnostic value of magnetic resonance imaging and technetium 99m-HMPAO single-photon-emission computed tomography for the diagnosis of Alzheimer disease in a community-dwelling elderly population.

The objective of this study was to assess the diagnostic value for Alzheimer disease (AD) of single-photon-emission computed tomography (SPECT) and magnetic resonance imaging (MRI), separately and in combination. The study was part of a two-stage population-based study of mental functioning among noninstitutionalized 65-to 85-year-olds living in Amsterdam, The Netherlands. Participants (n = 51) were randomly selected within strata of cognitive function to obtain a sample of AD patients (n = 10) and clinically normal subjects (n = 41), of whom 22 displayed some cognitive impairment and fulfilled criteria for "minimal dementia" according to the Cambridge Examination for Mental Disorders of the Elderly. Coronal T1-weighted MRI was used to visualize the medial temporal lobe. Medial temporal lobe atrophy (MTA) was assessed qualitatively on a 0-4 scale. Regional cerebral blood flow on SPECT was assessed with the use of technetium 99m-HMPAO in three manually drawn regions of interest (frontal, parietal, and temporoparietal). Ratios were calculated by using the cerebellum as the reference area. MTA differed significantly between AD patients and clinically normal subjects (p = 0.0009), with sensitivity for AD of 70% and a specificity of 76%. None of the three SPECT ratios differed between normal and AD subjects. The temporoparietal/cerebellar ratio had a sensitivity of 30% and a specificity of 71% as a cutoff of 0.76. When both tests were positive the combined sensitivity was low (20%), but the false-positive rate was also very low (5%). A negative result on MRI or any SPECT ratio yielded a high specificity (93%-98%) but also a high false-negative rate (60-80%). Adding SPECT to MRI seems useful only if a diagnosis of AD is suspected clinically and confirmation is needed. When the clinical probability that AD is absent is high, normal results on either MRI or SPECT may confirm this notion. Given the fact that structural imaging should be performed in a clinical workup for dementia, using MRI only would be the most cost-effective approach.

Aged↗

Birth weight, growth, and blood pressure: an annual follow-up study of children aged 5 through 21 years.

Associations between birth weight and blood pressure have been found in children and adults. In this longitudinal study, the objective was to assess the relation between birth weight and blood pressure level and the change in blood pressure from childhood and young adolescence into adulthood. A cohort of 483 children from a middle-class community in the town of Zoetermeer in the Netherlands had annual measurements of blood pressure during an average follow-up period of 14 years. For 330 of these participants, initially aged 5 through 21 years, birth weight data were collected, which were related to blood pressure level and blood pressure change. An inverse association between birth weight and systolic blood pressure was found, with adjustment for current body height and weight, sex, and use of alcohol, cigarettes, and oral contraceptives. This inverse association was found for the total follow-up in 5- to 37- year-olds (regression coefficient: -2.4 mm Hg/kg; 95% confidence interval: -3.9 to -1.0, as well as in most individual age groups: 5 through 9 years (-0.6 mm Hg/kg, -3.2 to 2.0); 10 through 14 years (-2.5 mm Hg/kg, -4.7 to -0.4); 15 through 19 years (-3.1 mm Hg/kg, -4.9 to -1.2); 20 through 24 years (-2.7 mm Hg/kg, -4.6 to -0.9); 25 through 29 years (-2.0 mm Hg/kg, -3.9 to -0.01); and 30 through 37 years (-1.9 mm Hg/kg, -4.6 to 0.7). For diastolic blood pressure, there appeared to be an inverse association with birth weight in the age group of 30 through 37 years, both unadjusted (-2.0 mm Hg/kg, -4.6 to 0.5) and adjusted for risk factors other than sex (-2.3 mm Hg/kg, -4.7 to 0.1), although these findings were of borderline statistical significance. The results were independent of gestational age and were similar in the group of subjects with low birth weight but normal gestational age (-2.7 mm Hg/kg, -4.3 to -1.0). In relation to systolic blood pressure, birth weight showed a significant interaction with body mass index (regression coefficient, 0.02; SE=0.01; P=.05). There was no relation between birth weight and change in systolic or diastolic blood pressure with age. Our longitudinal study shows that birth weight is consistently inversely associated with systolic blood pressure level from childhood to young adulthood and with diastolic blood pressure in young adulthood. Birth weight is not related to change of blood pressure with increasing age. Low birth weight in combination with high current body mass index seems to be of particular importance in the development of high blood pressure.

Adolescent↗

Dietary antioxidants and cognitive function in a population-based sample of older persons. The Rotterdam Study.

Antioxidants have been implicated in processes related to atherosclerosis, aging, and selective neuronal damage, all of which may ultimately affect cognitive function. In a sample of older persons, the authors examined the cross-sectional relation between cognitive function and dietary intake of beta-carotene and vitamins C and E. The data were derived from 5,182 community participants aged 55-95 years in the population-based Rotterdam Study in the period 1990 to 1993. Dietary intake was estimated from a semi-quantitative food frequency questionnaire and categorized into five levels of intake. Cognitive function was measured with the 30-point Mini-Mental State Examination (MMSE) and characterized as unimpaired (> 25 points) or impaired (< or = 25 points). Logistic regression analysis was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for cognitive impairment. After adjustment for age, education, sex, smoking, total caloric intake, and intake of other antioxidants, a lower intake of beta-carotene was associated with impaired cognitive function (< 0.9 mg vs. > or = 2.1 mg intake, OR = 1.9, 95% CI 1.2-3.1; p for trend < 0.04). There was no association between cognitive function and intake of vitamins C and E. These cross-sectional observations are compatible with the view that beta-carotene-rich foods may protect against cognitive impairment in older people. The finding could also reflect unmeasured confounding, measurement error, or a change in food habits that resulted from rather than preceded the onset of cognitive impairment.

Aged↗

Smoking, drinking, and thinking. The Zutphen Elderly Study.

The authors examine the cross-sectional and longitudinal relation of smoking habits and current alcohol intake to cognitive status and decline over a 3-year period as well as the extent to which these relations are modified by the presence of clinical conditions indicating atherosclerosis (cardiovascular disease (CVD)/diabetes). Data are from the cohort of men followed in the longitudinal Zutphen Elderly Study in 1990 (n = 489) and 1993 (n = 333). Cognitive function was measured in 1990 and 1993 with the 30-point Mini-Mental State Examination (MMSE). After adjustment for age, education, and alcohol intake, current smokers made 20% more errors on the MMSE than never smokers in the cross-sectional analyses. Cognitive decline was greatest in those with CVD/diabetes who currently smoked and never smoked (-1.9 and -1.3 points, respectively). After adjustment for age, education, and smoking status, men with CVD/diabetes and low-to-moderate alcohol intake had a significantly lower risk for poor cognitive function (MMSE < or = 25) than abstainers (odds ratios of 0.3 for less than one drink and 0.2 for one to two drinks per day). Alcohol intake was not associated with cognitive decline. These findings do not support the hypothesis of a protective effect of smoking on cognitive function; they suggest that smoking may be harmful among those with CVD/diabetes. Alcohol may result in an acute beneficial effect on cognitive function among those with CVD/diabetes. However, selection bias and unmeasured confounding should be of concern when evaluating these results.

Age Factors↗