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1.  Development and validation of a brief dementia screening indicator for primary care 
Background
Detection of “any cognitive impairment” is mandated as part of the Medicare annual wellness visit, but screening all patients may result in excessive false positives.
Methods
We developed and validated a brief Dementia Screening Indicator using data from four large, ongoing cohort studies (the Cardiovascular Health Study [CHS]; the Framingham Heart Study [FHS]; the Health and Retirement Study [HRS]; the Sacramento Area Latino Study on Aging [SALSA]) to help clinicians identify a subgroup of high-risk patients to target for cognitive screening.
Results
The final Dementia Screening Indicator included age (1 point/year; ages, 65–79 years), less than 12 years of education (9 points), stroke (6 points), diabetes mellitus (3 points), body mass index less than 18.5 kg/m2 (8 points), requiring assistance with money or medications (10 points), and depressive symptoms (6 points). Accuracy was good across the cohorts (Harrell’s C statistic: CHS, 0.68; FHS, 0.77; HRS, 0.76; SALSA, 0.78).
Conclusions
The Dementia Screening Indicator is a simple tool that may be useful in primary care settings to identify high-risk patients to target for cognitive screening.
doi:10.1016/j.jalz.2013.11.006
PMCID: PMC4119094  PMID: 24491321
Dementia; Screening; Risk prediction modeling; Primary care
2.  Type 2 Diabetes and 10-Year Risk of Dementia and Cognitive Impairment Among Older Mexican Americans 
Diabetes Care  2013;36(9):2600-2606.
OBJECTIVE
Type 2 diabetes has been linked with increased risk of dementia and cognitive impairment among older adults and with premature mortality in young and middle-aged adults. No studies have evaluated the association between diabetes and dementia among Mexican Americans, a population with a high burden of diabetes. We evaluated the association of diabetes with incidence of dementia and cognitive impairment without dementia (CIND) among older Mexican Americans while accounting for competing risk from death.
RESEARCH DESIGN AND METHODS
This study included 1,617 participants 60–98 years of age from the Sacramento Area Latino Study on Aging followed up to 10 years from 1998. We evaluated the association between diabetes and dementia/CIND with competing risk regression models.
RESULTS
Participants free of dementia/CIND at baseline (n = 1,617) were followed annually up to 10 years. There were 677 (41.9%) participants with diabetes, 159 (9.8%) incident dementia/CIND cases, and 361 (22.3%) deaths. Treated and untreated diabetes (hazard ratio 2.12 [95% CI 1.65–2.73] and 2.15 [1.58–2.95]) and dementia/CIND (2.48 [1.75–3.51]) were associated with an increased risk of death. In models adjusted for competing risk of death, those with treated and untreated diabetes had an increased risk of dementia/CIND (2.05 [1.41–2.97] and 1.55 [0.93–2.58]) compared with those without diabetes.
CONCLUSIONS
These findings provide evidence that the association between type 2 diabetes and dementia/CIND among Mexican Americans remains strong after accounting for competing risk of mortality. Treatments that modify risk of death among those with diabetes may change future dementia risk.
doi:10.2337/dc12-2158
PMCID: PMC3747945  PMID: 23514732
3.  Impact of Acculturation on Cardiovascular Risk Factors Among Elderly Mexican Americans 
Annals of epidemiology  2014;24(10):714-719.
Purpose
Higher levels of acculturation among Latinos have been shown to be associated with a higher prevalence of cardiovascular risk factors in some studies of middle age persons. The association of acculturation and prevalence of cardiovascular (CV) risk factors in elderly Latinos is less well established.
Methods
Acculturation was measured using the validated bidimensional Acculturation Rating Scale for Mexican Americans-II. We conducted a cross-sectional analysis of the association of acculturation with prevalence of CV risk factors among 1,789 elderly men and women from the Sacramento Area Latino Study on Aging (SALSA) using multivariate linear and logistic regression. We tested for the interaction of acculturation with risk factors by nativity status.
Results
Median age was 69.8. Higher acculturation was associated with lower systolic blood pressure, lower LDL, higher HDL, and lower prevalence of cardiovascular disease after age and sex adjustment. Higher acculturation remained associated with lower LDL and higher HDL levels after full adjustment. Nativity status did not affect these results.
Conclusions
Contrary to other reports in middle-aged persons, higher levels of acculturation were associated with better lipid profiles and no significant differences in other CV risk factors by acculturation level in elderly Latinos.
doi:10.1016/j.annepidem.2014.07.011
PMCID: PMC4170012  PMID: 25172232
Hispanics; Acculturation; Cardiovascular risk factors
4.  Immigrant Generation and Diabetes Risk Among Mexican Americans: The Sacramento Area Latino Study on Aging 
American journal of public health  2013;103(5):e45-e52.
Objectives
We examined whether acculturation and immigrant generation, a marker for assimilation, are associated with diabetes risk in an aging Mexican-origin population.
Methods
We analyzed data on 1789 adults aged 60 to 101 years from the Sacramento Area Latino Study on Aging. We ascertained type 2 diabetes on the basis of diabetic medication use, self-report of physician diagnosis, or a fasting glucose of 126 milligrams/deciliter or greater. Logistic regression modeled prevalent diabetes.
Results
Adjusting for age and gender, we observed significant but divergent associations between immigrant generation, acculturation, and diabetes risk. Relative to first-generation adults, second-generation adults had an odds ratio (OR) of 1.8 (95% confidence interval [CI] = 1.4, 2.4) and third-generation adults had an OR of 2.1 (95% CI = 1.4, 3.1) of having diabetes. Greater US acculturation, however, was associated with a slightly decreased diabetes rate. In the full model adjusting for socioeconomic and lifestyle factors, the association between generation (but not acculturation) and diabetes remained significant.
Conclusions
Our study lends support to the previously contested notion that assimilation is associated with an increased diabetes risk in Mexican immigrants. Researchers should examine the presence of a causal link between assimilation and health more closely.
doi:10.2105/AJPH.2012.300969
PMCID: PMC3686633  PMID: 23488481
5.  Immigrant Generation and Diabetes Risk Among Mexican Americans: The Sacramento Area Latino Study on Aging 
American journal of public health  2014;104(0 2):S234-S250.
Objectives
We examined whether acculturation and immigrant generation, a marker for assimilation, are associated with diabetes risk in an aging Mexican-origin population.
Methods
We analyzed data on 1789 adults aged 60 to 101 years from the Sacramento Area Latino Study on Aging. We ascertained type 2 diabetes on the basis of diabetic medication use, self-report of physician diagnosis, or a fasting glucose 126 milligrams/deciliter or greater. Logistic regression modeled prevalent diabetes.
Results
Adjusting for age and gender, we observed significant but divergent associations between immigrant generation, acculturation, and diabetes risk. Relative to first-generation adults, second-generation adults had an odds ratio OR) of 1.8 (95% confidence interval [CI] = 1.4, 2.4) and third-generation adults had an OR of 2.1 (95% CI = 1.4, 3.1) of having diabetes. Greater US acculturation, however, was associated with a slightly decreased diabetes rate. In the full model adjusting for socioeconomic and lifestyle factors, the association between generation (but not acculturation) and diabetes remained significant.
Conclusions
Our study lends support to the previously contested notion that assimilation is associated with an increased diabetes risk in Mexican immigrants. Researchers should examine the presence of a causal link between assimilation and health more closely.
doi:10.2105/AJPH.2012.300969r
PMCID: PMC4396826  PMID: 24899459
6.  Racial/Ethnic Differences in Dementia Risk Among Older Type 2 Diabetic Patients: The Diabetes and Aging Study 
Diabetes Care  2014;37(4):1009-1015.
OBJECTIVE
Although patients with type 2 diabetes have double the risk of dementia, potential racial/ethnic differences in dementia risk have not been explored in this population. We evaluated racial/ethnic differences in dementia and potential explanatory factors among older diabetic patients.
RESEARCH DESIGN AND METHODS
We identified 22,171 diabetic patients without preexisting dementia aged ≥60 years (14,546 non-Hispanic whites, 2,484 African Americans, 2,363 Latinos, 2,262 Asians, 516 Native Americans) from the Kaiser Permanente Northern California Diabetes Registry. We abstracted prevalent medical history (1 January 1996 to 31 December 1997) and dementia incidence (1 January 1998 to 31 December 2007) from medical records and calculated age-adjusted incidence densities. We fit Cox proportional hazards models adjusted for age, sex, education, diabetes duration, and markers of clinical control.
RESULTS
Dementia was diagnosed in 3,796 (17.1%) patients. Age-adjusted dementia incidence densities were highest among Native Americans (34/1,000 person-years) and African Americans (27/1,000 person-years) and lowest among Asians (19/1,000 person-years). In the fully adjusted model, hazard ratios (95% CIs) (relative to Asians) were 1.64 (1.30–2.06) for Native Americans, 1.44 (1.24–1.67) for African Americans, 1.30 (1.15–1.47) for non-Hispanic whites, and 1.19 (1.02–1.40) for Latinos. Adjustment for diabetes-related complications and neighborhood deprivation index did not change the results.
CONCLUSIONS
Among type 2 diabetic patients followed for 10 years, African Americans and Native Americans had a 40–60% greater risk of dementia compared with Asians, and risk was intermediate for non-Hispanic whites and Latinos. Adjustment for sociodemographics, diabetes-related complications, and markers of clinical control did not explain observed differences. Future studies should investigate why these differences exist and ways to reduce them.
doi:10.2337/dc13-0215
PMCID: PMC3964496  PMID: 24271192
7.  Life-span Socioeconomic Trajectory, Nativity, and Cognitive Aging in Mexican Americans: The Sacramento Area Latino Study on Aging 
Objectives.
Early life circumstances influence health across the life span. Migration and ethnicity may modify the lifetime trajectory of socioeconomic status (SES) and lead to heterogeneity in cognitive aging in later life.
Methods.
We examined the effects of both lifetime socioeconomic trajectory and cumulative disadvantage from childhood through adulthood on late life cognitive performance in a 9-year cohort of 1,789 Mexican Americans aged 60–100 years in 1998–1999.
Results.
Compared with those with low SES sustained over the life course, we found that those with more advantaged lifetime SES trajectories experienced fewer declines on a test of global cognitive function and a short-term verbal memory test. These associations are larger in first- and second-generation immigrant families.
Discussion.
Heterogeneity of cognitive aging among diverse race/ethnic groups may be influenced by intergenerational changes in SES, cultural norms, and behaviors and changes in health related to changes in the social and physical environment.
doi:10.1093/geronb/gbq071
PMCID: PMC3132761  PMID: 21743044
Acculturation; Cognition; Epidemiology; Life course and developmental change
9.  Impact of Gender and Blood Pressure on Post-Stroke Cognitive Decline among Older Latinos 
Background
Post-stroke cognitive decline (PSCD) is an important consequence of stroke that may be more severe in women than men. The existence of any gender differences in PSCD among Mexican Americans, and their potential mechanisms, such as blood pressure (BP), remain unknown. We assessed PSCD stratified on gender in older Mexican Americans and explored the influence of pre-stroke and post-stroke systolic BP on PSCD.
Methods
Among 1,576 non-demented, stroke-free adults 60 years or older when recruited in 1998–99 in the Sacramento Area Latino Study on Aging (SALSA) cohort, we examined pre-stroke and post-stroke longitudinal changes in Spanish English Verbal Learning test scores (WL), a verbal memory test, and errors on the Modified Mini Mental State Exam (3MSE) scores, a global cognition test, stratified by gender, adjusting for baseline and time-varying covariates with linear mixed-effects models.
Results
We identified 151 adults (mean age, 72 ± 8 years) with incident first-ever stroke during ten years of follow-up. After adjustment for age, education and time-varying depressive symptoms, 3MSE errors increased by 22%/year (95% CI, 6.8%–36.7%) in men and 13.2%/year (95% CI, 3.5%–22.9%) in women over the post-stroke period. Post-stroke WL scores improved by 0.05 words/year (95% CI, −0.24–0.33) in men and by 0.09 words/year (95% CI, −0.16–0.34) in women. Results persisted after adjustment for time-varying systolic BP.
Conclusions
Among this population of older Mexican Americans, PSCD did not differ by gender. We found no evidence that systolic BP influenced PSCD in women or men.
doi:10.1016/j.jstrokecerebrovasdis.2012.05.004
PMCID: PMC4030756  PMID: 22748715
[MeSH] Cerebrovascular disease/stroke; Cognition; Hispanic Americans; Sex; Epidemiology
10.  Are Health-Related Quality-of-Life and Self-Rated Health Associated with Mortality? Insights from Translating Research Into Action for Diabetes (TRIAD) 
Primary care diabetes  2009;3(1):37-42.
Aims
To determine if health-related quality-of-life and self-rated health are associated with mortality in persons with diabetes.
Methods
Survey and medical record data were obtained from 7,892 patients with diabetes in Translating Research Into Action for Diabetes (TRIAD), a multicenter prospective observational study of diabetes care in managed care. Vital status at follow-up was determined from the National Death Index. Multivariable proportional hazards models were used to determine if a generic measure of health-related quality-of-life (EQ-5D) and self-rated health measured at baseline were associated with 4-year all-cause, cardiovascular, and noncardiovascular mortality.
Results
At baseline, the mean EQ-5D score for decedents was 0.73 (SD=0.20) and for survivors was 0.81 (SD=0.18) (p<0.0001). Fifty-five percent of decedents and 36% of survivors (p<0.0001) rated their health as fair or poor. Lower EQ-5D scores and fair or poor self-rated health were associated with higher rates of mortality after adjusting for the demographic, socioeconomic, and clinical risk factors for mortality.
Conclusions
Health-related quality-of-life and self-rated health predict mortality in persons with diabetes. Health-related quality-of-life and self-rated health may provide additional information on patient risk independent of demographic, socioeconomic, and clinical risk factors for mortality.
doi:10.1016/j.pcd.2009.01.001
PMCID: PMC4138696  PMID: 19269911
diabetes; mortality; QoL
11.  Immigrant Generation and Diabetes Risk Among Mexican Americans: The Sacramento Area Latino Study on Aging 
Objectives
We examined whether acculturation and immigrant generation, a marker for assimilation, are associated with diabetes risk in an aging Mexican-origin population.
Methods
We analyzed data on 1789 adults aged 60 to 101 years from the Sacramento Area Latino Study on Aging. We ascertained type 2 diabetes on the basis of diabetic medication use, self-report of physician diagnosis, or a fasting glucose of 126 milligrams/deciliter or greater. Logistic regression modeled prevalent diabetes.
Results
Adjusting for age and gender, we observed significant but divergent associations between immigrant generation, acculturation, and diabetes risk. Relative to first-generation adults, second-generation adults had an odds ratio (OR) of 1.8 (95% confidence interval [CI] = 1.4, 2.4) and third-generation adults had an OR of 2.1 (95% CI = 1.4, 3.1) of having diabetes. Greater US acculturation, however, was associated with a slightly decreased diabetes rate. In the full model adjusting for socioeconomic and lifestyle factors, the association between generation (but not acculturation) and diabetes remained significant.
Conclusions
Our study lends support to the previously contested notion that assimilation is associated with an increased diabetes risk in Mexican immigrants. Researchers should examine the presence of a causal link between assimilation and health more closely.
PMCID: PMC4096955  PMID: 24096980
12.  REDUCED HEART RATE VARIABILITY IS ASSOCIATED WITH WORSE COGNITIVE PERFORMANCE IN ELDERLY MEXICAN AMERICANS 
Hypertension  2013;63(1):181-187.
Reduced Heart Rate Variability is a strong predictor of cardiovascular risk factors, cardiovascular events and mortality; and thus may be associated with cognitive neurodegeneration. Yet this has been relatively unexplored, particularly in minority populations with high cardiovascular burden. We used data from the Sacramento Area Latino Study on Aging to examine the cross-sectional association of reduced heart rate variability with cognitive function among elderly Mexican Americans. A total of 869 participants (mean age of 75 years; 59% females) had their 6-minute heart rate variability measured using an ECG monitor and respiration pacer in response to deep breathing. We used the Mean Circular Resultant, known as R bar, as a measure of heart rate variability and categorized it into quartiles (Q1 to Q4 of R bar: reduced to high heart rate variability). Cognitive function was assessed using the Modified Mini Mental State Exam, a 100-point test of global cognitive function and the Spanish and English Verbal Learning Test, a 15-point test of verbal memory recall. In fully-adjusted linear regression models, participants in quartile 1 had a 4-point lower Modified Mini Mental State Exam score (p<0.01), those in quartile 2 had 2-point lower score (p=0.04), and those in quartile 3 had 1-point lower score (p=0.35), as compared to those in the highest quartile of R bar. Reduced R bar was not associated with verbal memory. Our results suggest that reduced heart rate variability is associated with worse performance on the test of global cognitive function, above and beyond traditional cardiovascular risk factors.
doi:10.1161/HYPERTENSIONAHA.113.01888
PMCID: PMC4045649  PMID: 24144650
Aging; autonomic function; cognition; epidemiology; heart rate variability
13.  Body Adiposity in Late Life and Risk of Dementia or Cognitive Impairment in a Longitudinal Community-Based Study 
Background
The association between body adiposity at older ages and the development of cognitive impairment is unclear.
Methods
The association of body mass index (BMI) and waist circumference in late life with incidence of cognitive impairment was prospectively examined in a cohort study of 1,351 Latinos, aged 60–101 and residents of the Sacramento, CA, area at study baseline. The status of dementia and “cognitive impairment but not demented” (CIND) was determined at baseline and at each of five follow-up examinations by a multistage assessment protocol. Incident cases of dementia and CIND were combined (dementia/CIND) for more than 8 years of follow-up. BMI was categorized as less than 25.0, 25.0–29.9 (overweight), and 30 kg/m2 or greater (obese). Waist circumference was categorized into sex-specific tertiles.
Results
Dementia/CIND was diagnosed in 110 (8.2%) participants. Compared with the lowest BMI category, overweight participants had a 48% decreased rate of dementia/CIND (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.30–0.91) and obese participants had a 61% decreased rate of dementia/CIND (HR = 0.39, 95% CI: 0.20–0.78). Rates of dementia/CIND for the middle and high tertile of waist circumference, compared with the low tertile, were 80% and 90% higher, respectively (adjusted HR = 1.8, 95% CI: 1.1–3.1, and adjusted HR = 1.9, 95% CI: 0.91–3.8).
Conclusions
Abdominal fat in late life appears to confer an increased risk for dementia/CIND, whereas overall obesity appears to be protective. This may reflect age-related changes in body composition and the association of visceral fat with metabolic dysregulation.
doi:10.1093/gerona/gln006
PMCID: PMC2691186  PMID: 19168781
Adiposity; Dementia; Cognitive impairment; Body mass index; Waist circumference
14.  C-reactive protein and rate of dementia in carriers and non carriers of Apolipoprotein APOE4 genotype 
Neurobiology of aging  2007;29(12):1774-1782.
Background
Those with an apolipoprotein APOE4 allele (APOE4) have lower C-reactive protein (CRP) than those without APOE4. Whether APOE4 modifies the effects of CRP on rate of all cause dementia, cognitive impairment or Alzheimer’s disease (AD) is not established.
Methods
All cause dementia and cognitive impairment without dementia (CIND) was determined over five follow up visits from 1998–2006 in an ongoing cohort of older Latinos. The association between high sensitivity CRP and dementia/CIND, all cause dementia and Alzheimer’s disease by APOE4 status was examined in semi-parametric survival models with covariate adjustments.
Results
CRP was significantly lower among those with APOE4 than in those without. Among those with APOE4, CRP was associated with lower rates of combined dementia/CIND (HR: 0.60, 95% CL: 0.20–0.91, p=0.03) from a fully adjusted model. Among those with no APOE4, there was no effect of CRP on dementia/CIND rates (HR: 0.94, 95% CL:0.67–1.33).
Conclusions
Lower CRP in those with APOE4 may reflect immune effects of the APOE4 genotype. Higher CRP in those with APOE4 may be a marker of better immune function, leading to lower rate of dementia and AD.
doi:10.1016/j.neurobiolaging.2007.04.020
PMCID: PMC2593150  PMID: 17540481
Apolipoprotein E; c-reactive protein; cognitive impairment; dementia incidence; Latino aging
15.  A multilevel intervention to increase community hospital use of alteplase for acute stroke (INSTINCT): a cluster-randomised controlled trial 
Lancet neurology  2012;12(2):139-148.
Summary
Background
Use of alteplase improves outcome in some patients with stroke. Several types of barrier frequently prevent its use. We assessed whether a standardised, barrier-assessment, multicomponent intervention could increase alteplase use in community hospitals in Michigan, USA.
Methods
In a cluster-randomised controlled trial, we selected adult, non-specialty, acute-care community hospitals in the Lower Peninsula of Michigan, USA. Eligible hospitals discharged at least 100 patients who had had a stroke per year, had less than 100 000 visits to the emergency department per year, and were not academic comprehensive stroke centres. Using a computer-generated randomisation sequence, we selected 12 matched pairs of eligible hospitals. Within pairs, the hospitals were allocated to intervention or control groups with restricted randomisation in January, 2007. Between January, 2007, and December, 2007, intervention hospitals implemented a multicomponent intervention that included qualitative and quantitative assessment of barriers to alteplase use and ways to address the findings, and provided additional support. The primary outcome was change in alteplase use in patients with stroke in emergency departments between the pre-intervention period (January, 2005, to December, 2006) and the post-intervention period (January, 2008, to January, 2010). Physicians in participating hospitals and the coordinating centre could not be masked to group assignment, but were masked to progress made in paired control hospitals. External medical reviewers who were masked to group assignment assessed outcomes. We did intention-to-treat (ITT) and target-population (without one pair that was excluded after randomisation) analyses. This trial is registered at ClinicalTrials.gov, number NCT00349479.
Findings
All 24 hospitals completed the study. Overall, 745 of 40 823 patients with stroke received intravenous alteplase treatment. In the ITT analysis, the proportion of patients with stroke who were admitted and treated with alteplase increased between the pre-intervention and post-intervention periods in intervention hospitals (89 [1·25%] of 7119 patients to 235 [2·79%] of 8419) to a greater extent than in control hospitals (99 [1·25%] of 7946 to 194 [2·10%] of 9222), but the difference between groups was not significant (relative risk [RR] 1·37, 95% CI 0·96–1·93; p=0·08). In the target-population analysis, the increase in alteplase use in intervention hospitals (59 [1·00%] of 5882 to 191 [2·62%] of 7288) was significantly greater than in control hospitals (65 [1·09%] of 5957 to 120 [1·72%] of 6989; RR 1·68, 95% CI 1·09–2·57; p=0·02), but was still clinically modest.
Interpretation
The intervention did not significantly increase alteplase use in patients with ischaemic stroke. The increase in use of alteplase in the target population was significant, but smaller than the effect to which the study was powered. Additional strategies to increase acute stroke treatment are needed.
doi:10.1016/S1474-4422(12)70311-3
PMCID: PMC3939784  PMID: 23260188
16.  Leptin, Mild Cognitive Impairment, and Dementia Among Elderly Women 
Background.
The association between obesity and dementia has been inconsistent, possibly due to changes in body composition often seen in old age. Leptin may be associated with better cognitive function. However, neuroprotection may be inhibited among obese subjects possibly due to leptin resistance. We sought to determine (i) if leptin is associated with risk of dementia or mild cognitive impairment (MCI) in a cohort of very old women, (ii) if this association is modified by obesity, and (iii) if leptin is a stronger risk factor compared with traditional anthropometric measures.
Methods.
We studied 579 older women (mean age 82.6 years) from the ongoing prospective cohort Study of Osteoporotic Fractures, who were dementia-free at year-16 examination (our study baseline). Leptin (ng/mL) was measured using year-16 frozen serum, and anthropometric measures were collected during the same visit. Diagnosis of dementia/MCI was determined at year-20 examination.
Results.
There was evidence for a multiplicative interaction between log leptin and categorical body mass index (p = .03). Among women with body mass index <25kg/m2 (n = 190), 1SD difference in log leptin (0.91ng/mL) was associated with 32% lower odds of dementia/MCI (OR = .68; 95% CI = .46, .99), after adjustment. The association was not significant among women with body mass index ≥25kg/m2 (n = 377). Traditional anthropometric measures such as weight, height, and body mass index were not associated with dementia/MCI.
Conclusions.
In this cohort of very old women, higher serum leptin was prospectively associated with lower odds of dementia/MCI in women with normal body mass index, but not in overweight or obese women. Leptin may be a better predictor of dementia/MCI than traditional anthropometric measures.
doi:10.1093/gerona/gls155
PMCID: PMC3598359  PMID: 22859388
Dementia; Elderly; Leptin; Obesity
17.  Association of Chronic Kidney Disease Detected by Creatinine and Cystatin C with Death and Cardiovascular Events among Elderly Mexican-Americans: The Sacramento Area Latino Study on Aging (SALSA) 
Background/Objectives
Chronic kidney disease (CKD) is diagnosed by serum creatinine, which is biased by muscle mass, age and race. We evaluated whether cystatin C, an alternative measure of kidney function, can detect high risk CKD among elderly Mexican-Americans.
Design
Longitudinal
Setting
Sacramento Area Study of Latinos (SALSA)
Participants
1,435 Mexican-Americans ages 60–101 with mean follow-up 6.8 years
Measurements
We estimated glomerular filtration rate (eGFR, ml/min/1.73m2)by creatinine and cystatin C, and classified persons into four mutually exclusive categories: (1) CKD neither (eGFRcreat ≥60 and eGFRcys ≥60); (2) CKD creatinine only (eGFRcreat <60 but eGFRcys ≥60); (3) CKD cystatin only (eGFRcreat ≥60 but eGFRcys <60); and (4) CKD both (eGFRcreat <60 and eGFRcys <60). We studied the association of each CKD classification with all-cause death and cardiovascular (CVD) death using Cox regression.
Results
At baseline, mean was age 71±7; 34% (N=481) were diabetic and 68% (N=980) hypertensive. Compared with persons with no CKD by either marker, persons with CKD both had the highest risks for death (HR 2.30, 1.78–2.98) and CVD death (HR 2.75, 1.96–3.86) after full adjustment. Persons with CKD by cystatin C only were also at increased risk for death, HR 1.91 (1.37–2.67) and for CVD death, HR 2.56 (1.64–3.99)) compared to no CKD. In contrast, persons with CKD by creatinine only were not at increased risk for CVD death (HR 1.39, 0.71–2.72), but remained at higher risk for all-cause death (HR 1.95, 1.27–2.98).
Conclusions
Cystatin C may be a useful alternative in addition to creatinine to detect high risk CKD in elderly Mexican Americans.
doi:10.1111/jgs.12040
PMCID: PMC3545054  PMID: 23252993
chronic kidney disease; Mexican-Americans; elderly; creatinine; cystatin C; cardiovascular disease
18.  The Association of Blood Pressure and Mortality Differs by Self-reported Walking Speed in Older Latinos 
Background.
In some older adults, higher blood pressure (BP) is associated with a lower risk of mortality. We hypothesized that higher BP would be associated with greater mortality in high-functioning elders and lower mortality in elders with lower functional status.
Methods.
Participants were 1,562 Latino adults aged 60–101 years in the Sacramento Area Latino Study on Aging. Functional status was measured by self-reported walking speed, and BP was measured by automatic sphygmomanometer. Death information was determined from vital statistics records.
Results.
There were 442 deaths from 1998 to 2010; 53% were cardiovascular. Mean BP levels (mmHg) varied across fast, medium, and slow walkers: 136, 139, and 140 mmHg (systolic), p = .02 and 75, 76, and 77 mmHg (diastolic), p = .08, respectively. The relationship between systolic BP and mortality varied by self-reported walking speed: The adjusted hazard ratio for mortality in slow walkers was 0.96 per 10 mmHg higher systolic BP (95% confidence interval: 0.89, 1.02) and 1.29 (95% confidence interval: 1.08, 1.55) in fast walkers (p value for interaction <.001). We found a similar pattern for diastolic BP, although the interaction did not reach statistical significance; the adjusted hazard ratio per 10 mmHg higher diastolic BP was 0.89 (95% confidence interval: 0.78, 1.02) in slow walkers and 1.20 (95% confidence interval: 0.82, 1.76) in fast walkers (p value for interaction = .06).
Conclusions.
In high-functioning older adults, elevated systolic BP is a risk factor for all-cause mortality. If confirmed in other studies, the assessment of functional status may help to identify persons who are most at-risk for adverse outcomes related to high BP.
doi:10.1093/gerona/glr245
PMCID: PMC3436088  PMID: 22389463
Blood pressure; Functional status; Latinos
19.  Rethinking the Association of High Blood Pressure with Mortality in Elderly Adults: The Impact of Frailty 
Archives of internal medicine  2012;172(15):1162-1168.
Background
The association of hypertension and mortality is attenuated in elderly adults. Walking speed, as a measure of frailty, may identify which elders are most at risk for the adverse effects of hypertension. We hypothesized that elevated blood pressure (BP) would be associated with a greater risk of mortality in faster, but not slower, walking older adults.
Methods
Participants included 2,340 persons ≥65 years in the National Health and Nutrition Examination Survey, 1999–2000 and 2001–2002. Mortality data was linked to death certificates in the National Death Index. Walking speed was measured over a 20-foot walk and classified as faster (≥ 0.8 meters/second, n=1,307), slower (n=790), or incomplete (n=243). Potential confounders included age, sex, race, survey year, lifestyle and physiologic variables, health conditions, and antihypertensive medications.
Results
There were 589 deaths through December 31st, 2006. The association of BP and mortality varied by walking speed. Among faster walkers, those with elevated systolic BP (≥140 mmHg) had a greater adjusted risk of mortality compared to those without (Hazard Ratio (HR): 1.35, 95% confidence interval (CI): 1.03, 1.77). Among slower walkers, neither elevated systolic nor diastolic BP (≥90 mmHg) was associated with mortality. In participants who did not complete the walk test, elevated BP was strongly and independently associated with a lower risk of death: HR: 0.38, 95% CI: 0.23, 0.62 (systolic) and HR: 0.10, 95% CI: 0.01, 0.81 (diastolic).
Conclusions
Walking speed could be a simple measure to identify elderly adults who are most at risk for adverse outcomes related to high BP.
doi:10.1001/archinternmed.2012.2555
PMCID: PMC3537835  PMID: 22801930
20.  Central Obesity, Leptin and Cognitive Decline: the Sacramento Area Latino Study on Aging 
Background/Aims
Central obesity is a risk factor for cognitive decline. Leptin is secreted by adipose tissue and has been associated with better cognitive function. Aging Mexican-Americans have higher levels of obesity than Non-Hispanic Whites, but no investigations examined the relationship between leptin and cognitive decline among them or the role of central obesity in this association.
Methods
We analyzed 1480 dementia-free older Mexican-Americans who were followed over ten years. Cognitive function was assessed every 12 to 15 months with the Modified Mini Mental State Exam (3MSE) and the Spanish and English Verbal Learning Test (SEVLT).
Results
For females with small waist circumference (≤35inches), an interquartile range (IQR) difference in leptin was associated with 35% less 3MSE errors and 22% less decline in SEVLT score over 10 years. For males with small waist circumference (≤40inches), an IQR difference in leptin was associated with 44% less 3MSE errors and 30% less decline in SEVLT score over 10 years. There was no association between leptin and cognitive decline among females or males with large waist circumference.
Conclusion
Leptin interacts with central obesity in shaping cognitive decline. Our findings provide valuable information about the effects of metabolic risk factors on cognitive function.
doi:10.1159/000339957
PMCID: PMC3483312  PMID: 22814127
Aging; cognition; obesity; leptin; longitudinal study; Mexican Americans
23.  Antibody Levels to Persistent Pathogens and Incident Stroke in Mexican Americans 
PLoS ONE  2013;8(6):e65959.
Background
Persistent pathogens have been proposed as risk factors for stroke; however, the evidence remains inconclusive. Mexican Americans have an increased risk of stroke especially at younger ages, as well as a higher prevalence of infections caused by several persistent pathogens.
Methodology/Principal
Findings Using data from the Sacramento Area Latino Study on Aging (n = 1621), the authors used discrete-time regression to examine associations between stroke risk and (1) immunoglobulin G antibody levels to Helicobacter pylori (H. pylori), Cytomegalovirus, Varicella Zoster Virus, Toxoplasma gondii and Herpes simplex virus 1, and (2) concurrent exposure to several pathogens (pathogen burden), defined as: (a) summed sero-positivity, (b) number of pathogens eliciting high antibody levels, and (c) average antibody level. Models were adjusted for socio-demographics and stroke risk factors. Antibody levels to H. pylori predicted incident stroke in fully adjusted models (Odds Ratio: 1.58; 95% Confidence Interval: 1.09, 2.28). No significant associations were found between stroke risk and antibody levels to the other four pathogens. No associations were found for pathogen burden and incident stroke in fully adjusted models.
Conclusions/Significance
Our results suggest that exposure to H. pylori may be a stroke risk factor in Mexican Americans and may contribute to ethnic differences in stroke risk given the increased prevalence of exposure to H. pylori in this population. Future studies are needed to confirm this association.
doi:10.1371/journal.pone.0065959
PMCID: PMC3682951  PMID: 23799066
24.  Helicobacter pylori Infection Is Associated With an Increased Rate of Diabetes 
Diabetes Care  2012;35(3):520-525.
OBJECTIVE
Chronic infections could be contributing to the socioeconomic gradient in chronic diseases. Although chronic infections have been associated with increased levels of inflammatory cytokines and cardiovascular disease, there is limited evidence on how infections affect risk of diabetes.
RESEARCH DESIGN AND METHODS
We examined the association between serological evidence of chronic viral and bacterial infections and incident diabetes in a prospective cohort of Latino elderly. We analyzed data on 782 individuals aged >60 years and diabetes-free in 1998–1999, whose blood was tested for antibodies to herpes simplex virus 1, varicella virus, cytomegalovirus, Helicobacter pylori, and Toxoplasma gondii and who were followed until June 2008. We used Cox proportional hazards regression to estimate the relative incidence rate of diabetes by serostatus, with adjustment for age, sex, education, cardiovascular disease, smoking, and cholesterol levels.
RESULTS
Individuals seropositive for herpes simplex virus 1, varicella virus, cytomegalovirus, and T. gondii did not show an increased rate of diabetes, whereas those who were seropositive for H. pylori at enrollment were 2.7 times more likely at any given time to develop diabetes than seronegative individuals (hazard ratio 2.69 [95% CI 1.10–6.60]). Controlling for insulin resistance, C-reactive protein and interleukin-6 did not attenuate the effect of H. pylori infection.
CONCLUSIONS
We demonstrated for the first time that H. pylori infection leads to an increased rate of incident diabetes in a prospective cohort study. Our findings implicate a potential role for antibiotic and gastrointestinal treatment in preventing diabetes.
doi:10.2337/dc11-1043
PMCID: PMC3322696  PMID: 22279028
25.  Effectiveness guidance document (EGD) for acupuncture research - a consensus document for conducting trials 
Background
There is a need for more Comparative Effectiveness Research (CER) to strengthen the evidence base for clinical and policy decision-making. Effectiveness Guidance Documents (EGD) are targeted to clinical researchers. The aim of this EGD is to provide specific recommendations for the design of prospective acupuncture studies to support optimal use of resources for generating evidence that will inform stakeholder decision-making.
Methods
Document development based on multiple systematic consensus procedures (written Delphi rounds, interactive consensus workshop, international expert review). To balance aspects of internal and external validity, multiple stakeholders including patients, clinicians and payers were involved.
Results
Recommendations focused mainly on randomized studies and were developed for the following areas: overall research strategy, treatment protocol, expertise and setting, outcomes, study design and statistical analyses, economic evaluation, and publication.
Conclusion
The present EGD, based on an international consensus developed with multiple stakeholder involvement, provides the first systematic methodological guidance for future CER on acupuncture.
doi:10.1186/1472-6882-12-148
PMCID: PMC3495216  PMID: 22953730
Comparative effectiveness research; Effectiveness guidance document; Acupuncture

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