Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics.

BACKGROUND/OBJECTIVES: A common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues. SUBJECTS/METHODS: TC genotype and its associations with indicators of B12 status, including total B12, holotranscobalamin (holoTC), methylmalonic acid and homocysteine, were evaluated in a cohort of elderly Latinos (N=554, age 60-93 years) from the Sacramento Area Latino Study on Aging (SALSA). RESULTS: The distribution of TC genotypes was 41.3% homozygous reference (776CC) and 11.6% homozygous variant (776GG). No differences between the homozygous genotypes were observed in total B12, holoTC, methylmalonic acid or homocysteine. The holoTC/total B12 ratio was lower in the 776GG group compared with the 776CC group (P=0.04). Significant interactions of TC genotype with total B12 (P=0.04) and with holoTC (P< or =0.03) were observed such that mean homocysteine concentrations and the odds ratios for hyperhomocysteinemia (>13 micromol/l) were higher in the 776CC subjects compared with all carriers of the G allele (776CG and 776GG combined) when total B12 (<156 pmol/l) or holoTC (<35 pmol/l) were low. CONCLUSIONS: This population of older Latinos has a lower prevalence of the TC 776GG variant than reported for Caucasian populations. The association between vitamin B12 and homocysteine concentrations is modified by TC 776 genotype. It remains to be determined whether the TC C776G polymorphism has a significant effect on the hematological and neurological manifestations of B12 deficiency or on vascular and other morbidities associated with hyperhomocysteinemia.

Fasting total homocysteine (tHcy) concentration and mortality in older Mexican Americans.

OBJECTIVES: This study examines the association between tHcy on cardiovascular and noncardiovascular mortality. DESIGN: Longitudinal study of 1,633 Mexican Americans age>60 years recruited in 1998. SETTING: Sacramento, California. MEASUREMENTS: Cox proportional models were used to estimate the effects of tHcy on mortality rate in the total sample and in a subgroup of subjects without a history of cardiovascular disease at baseline. RESULTS: About half of the cohort was born in Mexico. Among Mexican-born participants, high tHcy (>11.0 micromol/L) was associated with a higher rate of cardiovascular mortality compared to those with low tHcy concentration

Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study.

OBJECTIVE: Evidence of a relation between use of lipid lowering drugs and cognitive outcomes is mixed. This study aimed to test the association between use of statins and incidence of dementia and cognitive impairment without dementia (CIND) over 5 years of follow-up. METHODS: Data were from a population-based cohort study comprising 1,789 older Mexican Americans. All participants had cognitive and clinical evaluations performed every 12 to 15 months. Participants who fell below specified cutpoints on cognitive tests were then evaluated clinically. Dementia diagnoses were finalized by an adjudication team. A total of 1,674 participants free of dementia/CIND at baseline were included in these analyses. Statin use was verified at each participant's home by medicine cabinet inspection. Cox proportional hazards models were used to evaluate the association between statin use and incidence of dementia/CIND. RESULTS: Overall, 452 of 1,674 participants (27%) took statins at any time during the study. Over the 5-year follow-up period, 130 participants developed dementia/CIND. In Cox proportional hazards models adjusted for education, smoking status, presence of at least one APOE epsilon4 allele, and history of stroke or diabetes at baseline, persons who had used statins were about half as likely as those who did not use statins to develop dementia/CIND (HR = 0.52; 95% CI 0.34, 0.80). CONCLUSION: Statin users were less likely to have incident dementia/cognitive impairment without dementia during a 5-year follow-up. These results add to the emerging evidence suggesting a protective effect of statin use on cognitive outcomes.

Central obesity and increased risk of dementia more than three decades later.

BACKGROUND: Numerous reports show that a centralized distribution of adiposity is a more dangerous risk factor for cardiovascular disease and diabetes than total body obesity. No studies have evaluated whether the same pattern exists with dementia. The objective was to evaluate the association between midlife central obesity and risk of dementia three decades later. METHODS: A longitudinal analysis was conducted of 6,583 members of Kaiser Permanente of Northern California who had their sagittal abdominal diameter (SAD) measured in 1964 to 1973. Diagnoses of dementia were from medical records an average of 36 years later, January 1, 1994, to June 16, 2006. Cox proportional hazard models adjusted for age, sex, race, education, marital status, diabetes, hypertension, hyperlipidemia, stroke, heart disease, and medical utilization were conducted. RESULTS: A total of 1,049 participants (15.9%) were diagnosed with dementia. Compared with those in the lowest quintile of SAD, those in the highest had nearly a threefold increased risk of dementia (hazard ratio, 2.72; 95% CI, 2.33-3.33), and this was only mildly attenuated after adding body mass index (BMI) to the model (hazard ratio, 1.92; 95% CI, 1.58-2.35). Those with high SAD (>25 cm) and normal BMI had an increased risk (hazard ratio, 1.89; 95% CI, 0.98-3.81) vs those with low SAD (<25 cm) and normal BMI (18.5-24.9 kg/m(2)), whereas those both obese (BMI >30 kg/m(2)) and with high SAD had the highest risk of dementia (HR, 3.60; 95% CI, 2.85-4.55). CONCLUSIONS: Central obesity in midlife increases risk of dementia independent of diabetes and cardiovascular comorbidities. Fifty percent of adults have central obesity; therefore, mechanisms linking central obesity to dementia need to be unveiled.

Cross-sectional correlates of fasting hyperinsulinaemia in post-menopausal women of different ethnic origin.

AIMS: In a large ethnically diverse nationwide sample of post-menopausal women we explored the relationship between fasting insulin levels, ethnicity, and a wide range of anthropometric, socio-economic, and lifestyle factors. METHODS: Subjects were post-menopausal women aged 50-79 years without diagnosed diabetes mellitus comprising a subsample (n = 3500) of the Women's Health Initiative (WHI) Clinical Trial and Observational Study. In a cross-sectional survey at baseline, we analysed the association between ethnicity and fasting insulin using analysis of covariance procedures and identified independent correlates of hyperinsulinaemia, defined by the 75th percentile cut point for each ethnic group. RESULTS: Fasting insulin levels were higher among African-American and Hispanic women than among non-Hispanic White or Asian women. These differences persisted after adjustment for age, educational attainment, total and central body obesity, adult weight change, family history of diabetes, smoking status, alcohol consumption, use of menopausal hormone therapy and physical activity. Higher levels of body mass index, waist-hip ratio, adult weight gain, and lower levels of total and moderate or strenuous recreational activity were independent correlates of fasting hyperinsulinaemia. Habitual walking was also inversely associated with fasting insulin. CONCLUSIONS: In this cross-sectional analysis, fasting insulin levels were higher among African-American and Hispanic post-menopausal women as compared with non-Hispanic White and Asian women. In addition, obesity, adult weight gain, and low levels of moderate or strenuous physical activity were independently associated with hyperinsulinaemia.

Low erythrocyte folate, but not plasma vitamin B-12 or homocysteine,is associated with dementia in elderly Latinos.

The relationship between B vitamin status and cognitive function has been of interest for many years. There is evidence of relationships between intake and status of folate and vitamin B-12 with neurological, cognitive, and memory impairment, but results have been inconsistent. Plasma B-12, erythrocyte folate, methylmalonic acid,and homocysteine were evaluated as predictors of cognitive function in a large population based sample of Latino elderly living in the Sacramento, California region. The hypothesis tested was that low folate and/or B-12 status predicts cognitive function impairment and dementia. Logistic regression was used to examine the differences in B-vitamin status by cognitive function category. Erythrocyte folate was related to dementia after controlling for age, gender, education, income, diabetes diagnosis, serum creatinine, and depressive symptoms. The highest prevalence of low erythrocyte folate occurred in the Dementia group and was significantly higher than in the Normal group. Plasma B-12, MMA, Hcy, and prevalence of a normal values for these variables, were not significantly different among the cognitive function classes. We conclude that folate status is associated with dementia but that more research is needed on the relationship between vitaminB-12 status, Hcy and cognitive function to explore possible associations with these parameters.

Preliminary evidence that estrogen protects against age-related hippocampal atrophy.

Few studies have examined gender differences in hippocampal volumes, and the potential effect of estrogen on these measures has not been well studied. We used MRI to measure hippocampal volumes in elderly Mexican American men and women subjects in order to determine if there were gender differences and if estrogen replacement therapy (ERT) had an effect on hippocampal volume in postmenopausal women. MRI measures of hippocampal volumes (normalized to intracranial volume) were compared in 59 women and 38 men. Further comparisons were made between men subjects, women subjects taking ERT, and women subjects not taking ERT. There were no significant effects of gender on normalized hippocampal volumes. However, women subjects taking ERT had larger right hippocampal volumes than women subjects not taking ERT and larger anterior hippocampal volumes than men subjects and women subjects not taking ERT. These findings suggest a neuroprotective effect of estrogen.

Body composition in the elderly: the influence of nutritional factors and physical activity.

BACKGROUND: Controversy exists regarding the relative contribution of diet and exercise to body composition. Few studies have examined these associations in the elderly, where changes occur in the body fat to muscle ratio. OBJECTIVE: The primary objective of this paper is to determine whether energy intake or physical activity are associated with body composition. Secondly, to investigate whether specific macronutrients are associated with fat or lean tissue. DESIGN: Data (n= 1404) for this cross-sectional analysis were collected from a population-based sub-sample of elderly enrollees in the Cardiovascular Health Study (CHS). Dietary intake and physical activity were assessed by questionnaires. Body composition was measured by Dual Energy X-ray Absorptiometry (DEXA). Linear regression models were used to assess the associations of diet and activity with body composition. RESULTS: Total energy intake was not associated with any of the body composition measures. Higher dietary saturated fat was associated with higher percent body mass as fat and trunk fat in both sexes (p<0.01), and in men other dietary fats were associated with body fat. In women, distance walked was inversely associated with fat masses even after adjustment for pace of walking. In both sexes, faster pace of walking was associated with lower body and fat mass (p<0.01). Lean muscle mass was not associated with physical activity or dietary intakes. CONCLUSION: Physical activity and dietary fat intake in this the elderly population were more closely associated with body fat mass than was total energy intake.

Brain function and cognition in a community sample of elderly Latinos.

BACKGROUND: Previous studies using PET to measure cerebral glucose metabolism in AD have found metabolic reductions in the temporoparietal and posterior cingulate cortices in individuals with dementia and those at risk of developing it. This study was designed to extend this finding to individuals selected from a population-based cohort of Mexican Americans with a wide spectrum of cognitive ability. METHODS: A group of 93 individuals was selected from the Sacramento Area Latino Study on Aging, and subjects were categorized into four groups of increasing levels of cognitive impairment: normal, memory impaired, cognitively impaired but not demented (CIND), and demented. PET was performed with the tracer [(18)F]-fluorodeoxyglucose, and data were analyzed with both statistical parametric mapping and an atrophy-corrected volume of interest approach. RESULTS: Individuals with dementia had metabolic reductions that were most robust in the posterior cingulate cortex, whereas CIND subjects had less statistically robust reductions in the posterior cingulate cortex. Cingulate hypometabolism increased the risk of dementia and was a significant risk factor for dementia in logistic regression models that also incorporated MR measures of hippocampal volume and white matter hyperintensities. CONCLUSION: Posterior cingulate cortical hypometabolism is clearly detected in individuals with dementia who are selected from a population with lower education and a high prevalence of cerebrovascular risk factors, supporting the generalizability of this finding. These metabolic reductions occur prior to the onset of dementia but only in those persons with relatively advanced symptoms.

Brain structure and cognition in a community sample of elderly Latinos.

BACKGROUND: Previous studies have found that hippocampal atrophy and white matter hyperintensities (WMH) on MRI are linked to cognitive impairment and dementia. The authors measured these variables in a population-based cohort of older Mexican Americans with a wide spectrum of cognitive ability, ranging from normal cognition to dementia. OBJECTIVE: To investigate whether these structural brain changes were seen in individuals prior to the development of dementia and how these changes were related to the presence of dementia. METHODS: A sample of 122 subjects was selected from the Sacramento Area Latino Study on Aging, and subjects were categorized into four groups of increasing levels of cognitive impairment: normal, memory impaired (MI), cognitively impaired but not demented (CIND), and demented. Hippocampal volume was quantified using a region of interest approach. WMH was rated on a semiquantitative scale as the percent of total volume of white matter. RESULTS: Hippocampal volume was significantly reduced in CIND and demented individuals, and WMH were significantly increased in demented subjects. MI subjects did not have any significant changes in hippocampal volume or WMH. The risk for developing dementia was significantly and comparably increased in subjects with either hippocampal atrophy or high WMH. However, the risk for dementia increased dramatically in subjects with both hippocampal atrophy and a high degree of WMH. CONCLUSION: Reductions in hippocampal volume may be present before dementia but not until cognitive impairment is relatively severe. Because there is a synergistic effect between high WMH and hippocampal atrophy, interactions between vascular and degenerative processes may be important determinants of dementia.

Acculturation and the prevalence of depression in older Mexican Americans: baseline results of the Sacramento Area Latino Study on Aging.

OBJECTIVE: To determine the association between acculturation, immigration, and prevalence of depression in older Mexican Americans. DESIGN: Cross-sectional analysis from a cohort study. SETTING: Urban and rural counties of the Central Valley of Northern California. PARTICIPANTS: One thousand seven hundred and eighty-nine Latinos recruited from a population-based sample (85% Mexican Americans) with a mean age of 70.6 (range 60-100; standard deviation (SD) = 7.13); 58.2% were women. MEASUREMENTS: Depressive symptoms were assessed with the Center for Epidemiologic Studies--Depression scale (CES-D). Acculturation was measured with the Acculturation Rating Scale for Mexican Americans--II. Psychosocial, behavioral, and medical histories were also obtained. RESULTS: The prevalence of depression (CES-D > or = 16) was 25.4%. Women were at greater risk (32.0%) than men (16.3%; male/female odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.90-3.09). The prevalence of depression was higher among immigrants (30.4%, OR = 1.70, 95% CI = 1.36-2.13), bicultural participants (24.2%, OR = 1.66, 95% CI = 1.24-2.24), and less-acculturated participants (36.1%, OR = 2.95, 95% CI = 2.22-3.93) compared with U.S.-born (20.5%) and more-acculturated groups (16.1%). When adjustments for education, income, psychosocial, behavioral, and health-problem factors were made, the least-acculturated participants were at significantly higher risk of depression than highly acculturated Mexican Americans (OR = 1.56, 95% CI = 1.06-2.31). CONCLUSIONS: These findings are consistent with previously reported estimates of a higher prevalence of depression for older Mexican Americans than non-Hispanic Caucasians and African Americans and are the first to report the prevalence and risk of depression for older U.S.-born and immigrant Mexican Americans. The high prevalence of depression of the least acculturated group may be related to cultural barriers encountered by immigrants and less-acculturated older Mexican Americans and to poorer health status.

A new verbal learning and memory test for English- and Spanish-speaking older people.

Word-list verbal learning and memory tests with appropriate normative data can be highly sensitive to cognitive decline, but there are significant limitations of such tests available for use with older Hispanic and non-Hispanic people living in the US. The purpose of this study was to (1) create a new word-list learning and memory test in both English and Spanish and, (2) validate it with respect to sensitivity to cognitive impairment, and (3) develop statistical corrections for the effects of significant demographic variables, including ethnicity, language of administration, age, education, and gender. A community dwelling sample of 801 English- and Spanish-speaking older people was employed. Recall on learning trials and the delayed recall trial of the word-list learning test were strongly related to the Mini-Mental State Examination (MMSE). moderately related to age, and weakly related to gender and education. The relationship of word-list variables and the MMSE did not significantly differ across ethnicity/language groups. Regression coefficients for demographic variables were used in a statistical correction formula to adjust raw word-list scores, and then to develop specific percentile cut-off values.

Factors associated with weight gain in women after diagnosis of breast cancer. Women's Healthy Eating and Living Study Group.

OBJECTIVE: To identify the factors associated with weight gain after diagnosis of breast cancer in a heterogeneous population of women. DESIGN: Descriptive cross-sectional study. SUBJECTS: 1,116 patients who had been diagnosed with stage I, stage II, or stage IIIA primary, operable breast cancer within the previous 4 years. Patients were recruited during enrollment into a diet intervention trial to reduce risk for breast cancer recurrence. Analysis Demographic data, weight history, and physical activity information obtained by questionnaire and medical information obtained by chart review; dietary assessment based on four 24-hour dietary recalls collected by telephone. Associations between weight change after the diagnosis of breast cancer and prediction variables were examined using univariate and multiple linear regression analyses. RESULTS: Overall, 60% of the subjects reported weight gain, 26% reported weight loss, and 14% reported no change in weight after the diagnosis of breast cancer. The overall mean weight change was a gain of 2.7 kg (6 lb). Factors positively and independently associated with weight gain were time since diagnosis of breast cancer, adjuvant chemotherapy, African-American ethnicity, current energy intake, and postmenopausal status at time of study entry. Factors inversely and independently associated with weight gain were prediagnosis body mass index, age at diagnosis, education level, and exercise index score. APPLICATIONS: Higher energy intake and lower level of physical activity are independently associated with increased risk for weight gain after the diagnosis of breast cancer. Strategies to modify these behaviors are likely to influence the long-term pattern of weight change.

The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons.

CONTEXT: Cognitive decline in elderly persons is often an early predictor of dementia. Subclinical cardiovascular disease (CVD) and diabetes mellitus may contribute to substantial decline in cognitive function in the elderly. These risks may be modified by gene-environment interactions between apolipoprotein E (APOE) genotype and CVD risk factors or subclinical CVD. OBJECTIVES: To examine the association between subclinical CVD and decline in cognitive functioning in the elderly and to examine effect modification by the APOE genotype of the association between subclinical disease and cognitive decline. DESIGN: The Cardiovascular Health Study, a population-based, prospective cohort study. SETTING AND POPULATION: A total of 5888 randomly selected Medicare-eligible participants from Sacramento County, California; Forsyth County, North Carolina; Washington County, Maryland; and Pittsburgh, Pa, aged 65 years or older, who were recruited in 1989-1990 (n = 5201) and in 1992-1993 (n = 687) and who were followed up for 7 and 5 years, respectively. MAIN OUTCOME MEASURES: Change over time in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test as a function of APOE genotype, subclinical CVD, and diabetes mellitus. RESULTS: Seventy percent of participants had no significant decline on the Modified Mini-Mental State Examination. Systolic blood pressure, the ankle-arm brachial index, atherosclerosis of the internal carotid artery, diabetes mellitus, and several diagnoses of prevalent CVD were significantly associated with declines in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test. The rate of cognitive decline associated with peripheral vascular disease, atherosclerosis of the common and internal carotid arteries, or diabetes mellitus was increased by the presence of any APOE epsilon4 allele. CONCLUSIONS: Most healthy elderly people did not experience cognitive decline. Measures of subclinical CVD were modest predictors of cognitive decline. Those with any APOE epsilon4 allele in combination with atherosclerosis, peripheral vascular disease, or diabetes mellitus were at substantially higher risk of cognitive decline than those without the APOE epsilon4 allele or subclinical CVD. High levels of atherosclerosis increased cognitive decline independently of APOE genotype.

Understanding changing risk factor associations with increasing age in adults.

With an increasingly older population, there is considerable interest in understanding the potential for risk factor interventions in order to prevent, postpone, or slow down the common diseases seen in older persons. However, it is often reported that the strength of association between risk factors and common disease outcomes decreases with increasing age. Actually, many different age-related patterns are observed. Understanding these patterns requires knowledge of issues related to the pathophysiology of aging, including age-related physiologic and metabolic alterations, detection and diagnosis of disease in the elderly, measurement of risk factors, sample selection, comorbidity, competing risks, selective survival, ceiling effects, and methods of analysis in aging populations.

Chart-recorded psychiatric diagnoses in women giving birth in California in 1992.

OBJECTIVE: Although major advances have been made in the diagnosis and treatment of mental disorders in primary care, few population-based investigations have focused on the obstetrical sector. This study examines the occurrence of chart-recorded psychiatric discharge diagnoses among all women delivering in California hospitals in 1992. METHOD: The authors undertook an archival analysis of the California Health Information for Policy Project data set, which consists of linked hospital discharge and birth certificate data for 580,282 deliveries. Frequencies of ICD-9 psychiatric diagnoses were ascertained. RESULTS: Among all women delivering, 1.5% received psychiatric or substance use diagnoses. Of diagnoses recorded, 75% were substance use disorders, 21% were classified generically as "mental disorder of pregnancy," and other psychiatric disorders accounted for 4%. CONCLUSIONS: The occurrence of psychiatric diagnoses in these women is markedly lower than expected, suggesting an underreporting of psychiatric disorders at delivery. Further investigations into the detection of mental disorders in the obstetrical sector are needed.

Trends in dementia-free life expectancy among elderly members of a large health maintenance organization.

BACKGROUND: This study examined the secular trends of life expectancy without dementia among elderly American members of a health maintenance organization, and observed if an increased life expectancy is accompanied by an increase in the duration of life with dementia. METHODS: The data derived from two chronological 9-year prospective cohort studies of members of the Kaiser Permanente Medical Care Program of Northern California. The first and second cohorts included 2,702 and 2,926 people aged > or =65 years free from dementia at baseline. Life expectancy without dementia or dementia-free life expectancy (DemFLE) is defined as the average number of years a person is expected to live without dementia. Total life expectancy is equal to the sum of DemFLE and life expectancy with dementia. Estimations of DemFLE were based on mortality data and incidence of dementia, using double-decrement life tables. RESULTS: Between the first and second cohorts, all-cause mortality rates declined, while the incidence of dementia remained constant in both men and women. Among the males, total life expectancy increased at a higher rate than DemFLE. Consequently, the duration of life with dementia was extended in the second cohort. Conversely, among the females DemFLE increased at a higher rate than total life expectancy, thus the duration of life with dementia decreased in the second cohort. The median age of dementia onset was postponed by 2-3 years in the second cohort for females, and did not show any specific difference between the two cohorts in males. CONCLUSION: The trends of health expectancies suggest an extension of the duration of life with dementia for males and a compression of dementia for females. A decreased incidence of risk factors for dementia among females in the second cohort such as stroke may explain these trends.