Assessing Bias in Cognitive Testing for Older Adults with Sensory Impairment: An Analysis of Differential Item Functioning in the Baltimore Longitudinal Study on Aging (BLSA) and the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).

OBJECTIVES: Vision and hearing impairments affect 55% of people aged 60+ years and are associated with lower cognitive test performance; however, tests rely on vision, hearing, or both. We hypothesized that scores on tests that depend on vision or hearing are different among those with vision or hearing impairments, respectively, controlling for underlying cognition. METHODS: Leveraging cross-sectional data from the Baltimore Longitudinal Study of Aging (BLSA) and the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS), we used item response theory to test for differential item functioning (DIF) by vision impairment (better eye presenting visual acuity worse than 20/40) and hearing impairment (better ear .5-4 kHz pure-tone average > 25 decibels). RESULTS: We identified DIF by vision impairment for tests whose administrations do not rely on vision [e.g., Delayed Word Recall both in ARIC-NCS: .50 logit difference between impaired and unimpaired (p = .04) and in BLSA: .62 logits (p = .02)] and DIF by hearing impairment for tests whose administrations do not rely on hearing [Digit Symbol Substitution test in BLSA: 1.25 logits (p = .001) and Incidental Learning test in ARIC-NCS: .35 logits (p = .001)]. However, no individuals had differences between unadjusted and DIF-adjusted measures of greater than the standard error of measurement. CONCLUSIONS: DIF by sensory impairment in cognitive tests was independent of administration characteristics, which could indicate that elevated cognitive load among persons with sensory impairment plays a larger role in test performance than previously acknowledged. While these results were unexpected, neither of these samples are nationally representative and each has unique selection factors; thus, replication is critical.

The effect of missing data and imputation on the detection of bias in cognitive testing using differential item functioning methods.

BACKGROUND: Item response theory (IRT) methods for addressing differential item functioning (DIF) can detect group differences in responses to individual items (e.g., bias). IRT and DIF-detection methods have been used increasingly often to identify bias in cognitive test performance by characteristics (DIF grouping variables) such as hearing impairment, race, and educational attainment. Previous analyses have not considered the effect of missing data on inferences, although levels of missing cognitive data can be substantial in epidemiologic studies. METHODS: We used data from Visit 6 (2016-2017) of the Atherosclerosis Risk in Communities Neurocognitive Study (N = 3,580) to explicate the effect of artificially imposed missing data patterns and imputation on DIF detection. RESULTS: When missing data was imposed among individuals in a specific DIF group but was unrelated to cognitive test performance, there was no systematic error. However, when missing data was related to cognitive test performance and DIF group membership, there was systematic error in DIF detection. Given this missing data pattern, the median DIF detection error associated with 10%, 30%, and 50% missingness was -0.03, -0.08, and -0.14 standard deviation (SD) units without imputation, but this decreased to -0.02, -0.04, and -0.08 SD units with multiple imputation. CONCLUSIONS: Incorrect inferences in DIF testing have downstream consequences for the use of cognitive tests in research. It is therefore crucial to consider the effect and reasons behind missing data when evaluating bias in cognitive testing.

Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

Vitamin D, vitamin D binding protein gene polymorphisms, race and risk of incident stroke: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND PURPOSE: Low vitamin D levels, measured by serum 25-hydroxyvitamin D [25(OH)D], are associated with increased stroke risk. Less is known about whether this association differs by race or D binding protein (DBP) single nucleotide polymorphism (SNP) status. Our objective was to characterize the associations of and interactions between 25(OH)D levels and DBP SNPs with incident stroke. It was hypothesized that associations of low 25(OH)D with stroke risk would be stronger amongst persons with genotypes associated with higher DBP levels. METHODS: 25(OH)D was measured by mass spectroscopy in 12 158 participants in the Atherosclerosis Risk in Communities (ARIC) study (baseline 1990-1992, mean age 57 years, 57% female, 23% black) and they were followed through 2011 for adjudicated stroke events. Two DBP SNPs (rs7041, rs4588) were genotyped. Cox models were adjusted for demographic/behavioral/socioeconomic factors. RESULTS: During a median of 20 years follow-up, 804 incident strokes occurred. The lowest quintile of 25(OH)D (<17.2 ng/ml) was associated with higher stroke risk [hazard ratio (HR) 1.34 (1.06-1.71) versus highest quintile]; this association was similar by race (P interaction 0.60). There was weak evidence of increased risk of stroke amongst those with 25(OH)D < 17.2 ng/ml and either rs7041 TG/GG [HR = 1.29 (1.00-1.67)] versus TT genotype [HR = 1.19 (0.94-1.52)] (P interaction 0.28) or rs4588 CA/AA [HR = 1.37 (1.07-1.74)] versus CC genotype [HR = 1.14 (0.91-1.41)] (P interaction 0.11). CONCLUSIONS: Low 25(OH)D is a risk factor for stroke. Persons with low 25(OH)D who are genetically predisposed to high DBP (rs7041 G, rs4588 A alleles), who therefore have lower predicted bioavailable 25(OH)D, may be at greater risk for stroke, although our results were not conclusive and should be interpreted as hypothesis generating.

Vitamin D and cognitive function and dementia risk in a biracial cohort: the ARIC Brain MRI Study.

BACKGROUND AND PURPOSE: Some recent studies in older, largely white populations suggest that vitamin D, measured by 25-hydroxyvitamin D [25(OH)D], is important for cognition, but such results may be affected by reverse causation. Measuring 25(OH)D in late middle age before poor cognition affects behavior may provide clearer results. METHODS: This was a prospective cohort analysis of 1652 participants (52% white, 48% black) in the Atherosclerosis Risk in Communities (ARIC) Brain MRI Study. 25(OH)D was measured from serum collected in 1993-1995. Cognition was measured by the delayed word recall test (DWRT), the digit symbol substitution test (DSST) and the word fluency test (WFT). Dementia hospitalization was defined by ICD-9 codes. Adjusted linear, logistic and Cox proportional hazards models were used. RESULTS: Mean age of participants was 62 years and 60% were female. Mean 25(OH)D was higher in whites than blacks (25.5 vs. 17.3 ng/ml, P < 0.001). Lower 25(OH)D was not associated with lower baseline scores or with greater DWRT, DSST or WFT decline over a median of 3 or 10 years of follow-up (P > 0.05). Over a median of 16.6 years, there were 145 incident hospitalized dementia cases. Although not statistically significant, lower levels of 25(OH)D were suggestive of an association with increased dementia risk [hazard ratio for lowest versus highest race-specific tertile: whites 1.32 (95% confidence interval 0.69, 2.55); blacks 1.53 (95% confidence interval 0.84, 2.79)]. CONCLUSIONS: In contrast to prior studies performed in older white populations, our study of late middle age white and black participants did not find significant associations between lower levels of 25(OH)D with lower cognitive test scores at baseline, change in scores over time or dementia risk.

Do systolic BP and pulse pressure relate to ventricular enlargement?

BACKGROUND AND PURPOSE: To evaluate the association between systolic, diastolic and pulse pressure, and increase in ventricular size (VS). Observations in laboratory animals suggest intraventricular pulse pressure (systolic-diastolic) may play a role in ventricular enlargement. METHODS: Initial magnetic resonance (MR) scans and vascular risk factors evaluation were performed in 1812 Atherosclerosis Risk in Communities participants in 1994-1995. In 2004-2006, 1130 participants underwent repeat MR. VS was rated using a validated nine-point scale. Multiple logistic regression analysis assessed association between blood pressure measures and pulse pressure, and the change between the MR scans of VS controlling for age, sex and race. RESULTS: At baseline 1112 participants (385 black women, 200 black men, 304 white women and 223 white men) had a mean age of 61.7 ± 4.3 years. In adjusted models pulse pressure at baseline was associated with an increase in VS [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.01-1.40], as was systolic pressure (OR 1.28, 95% CI 1.03-1.58). CONCLUSIONS: Systolic pressure and pulse pressure are associated with future development of increased VS. The findings are consistent with the animal literature that increased pulse pressure predisposes to risk of future increased VS. High pulse pressure might play a role in the pathogenesis of normal pressure hydrocephalus.

Glycated haemoglobin and cognitive decline: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: This study aimed to examine the association between diabetes and hyperglycaemia-assessed by HbA(1c)-and change in cognitive function in persons with and without diabetes. METHODS: This was a prospective cohort study of 8,442 non-diabetic and 516 diabetic participants in the Atherosclerosis Risk in Communities (ARIC) study. We examined the association of baseline categories of HbA(1c) with 6 year change in three measures of cognition: the digit symbol substitution test (DSST); the delayed word recall test (DWRT); and the word fluency test (WFT). Our primary outcomes were the quintiles with the greatest annual cognitive decline for each test. Logistic regression models were adjusted for demographic (age, sex, race, field centre, education, income), lifestyle (smoking, drinking) and metabolic (adiposity, blood pressure, cholesterol) factors. RESULTS: The mean age was 56 years. Women accounted for 56% of the study population and 21% of the study population were black. The mean HbA(1c) was 5.7% overall: 8.5% in persons with and 5.5% in persons without diabetes. In adjusted logistic regression models, diagnosed diabetes was associated with cognitive decline on the DSST (OR 1.42, 95% CI 1.14-1.75, p = 0.002), but HbA(1c) was not a significant independent predictor of cognitive decline when stratifying by diabetes diagnosis (diabetes, p trend = 0.320; no diabetes, p trend = 0.566). Trends were not significant for the DWRT or WFT in either the presence or the absence of diabetes. CONCLUSIONS/INTERPRETATION: Hyperglycaemia, as measured by HbA(1c), did not add predictive power beyond diabetes status for 6 year cognitive decline in this middle-aged population. Additional work is needed to identify the non-glycaemic factors by which diabetes may contribute to cognitive decline.

Association of lung function with cognitive decline and dementia: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Previous studies reported a higher risk of cognitive decline and dementia amongst individuals with impaired lung function. However, many did not adjust for important confounders or did not include women and non-whites. METHODS: We studied 10,975 men and women aged 47-70 years (23% African-Americans) enrolled in the Atherosclerosis Risk in Communities Study. Pulmonary function tests and a cognitive assessment, including the Delayed Word Recall, the Digit Symbol Substitution, and the World Fluency Tests, were carried out in 1990-1992. Repeated cognitive assessments were performed in 1996-1998 for the entire cohort, and in 1993-1995, and 2004-2006 in 904 eligible individuals. Dementia hospitalization was ascertained through 2005. RESULTS: In analysis adjusted for lifestyles, APOE genotype, and cardiovascular risk factors, impaired lung function was associated with worse cognitive function at baseline. No association was found between lung function and cognitive decline over time. Impaired lung function at baseline was associated with higher risk of dementia hospitalization during follow-up, particularly amongst younger individuals. The hazard ratios (95% confidence intervals) of dementia hospitalization were 1.6 (0.9, 2.8) and 2.1 (1.2, 3.7) comparing the lowest with the highest quartile of forced expiratory volume in 1 s and forced vital capacity, respectively. Presence of a restrictive ventilatory pattern, but not of an obstructive pattern, was associated with reduced cognitive scores and higher dementia risk. CONCLUSION: Reduced lung function was associated with worse performance in cognitive assessments and with an increased risk of dementia hospitalization. Future research should determine whether maintaining optimal pulmonary health might prevent cognitive impairment and dementia.

Risk of dementia hospitalisation associated with cardiovascular risk factors in midlife and older age: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Cardiovascular risk factors are associated with a higher risk of developing dementia. Studies in older populations, however, have often failed to show this relationship. We assessed the association between cardiovascular risk factors measured in midlife and risk of being hospitalised with dementia and determined whether this association was modified by age and ethnicity. METHODS: We studied 11 151 participants in the population-based Atherosclerosis Risk in Communities cohort, aged 46-70 (23% African-Americans) in 1990-2, when participants underwent a physical exam and cognitive testing. Hospitalisations with dementia were ascertained through December 2004. RESULTS: During follow-up, 203 cases of hospitalisation with dementia were identified. Smoking (hazard ratio (HR), 95% CI 1.7, 1.2 to 2.5), hypertension (HR, 95% CI 1.6, 1.2 to 2.2) and diabetes (HR, 95% CI 2.2, 1.6 to 3.0) were strongly associated with dementia, in Caucasians and African-Americans. These associations were stronger when risk factors were measured at a younger age than at an older age. In analyses including updated information on risk factors during follow-up, the HR of dementia in hypertensive versus non-hypertensive participants was 1.8 at age <55 years compared with 1.0 at age 70+ years. Parallel results were observed for diabetes (HR 3.4 in <55, 2.0 in >or=70), smoking (4.8 in <55, 0.5 in >or=70) and hypercholesterolaemia (HR 1.7 in <55, 0.9 in >or=70) CONCLUSION: In this prospective study, smoking, hypertension and diabetes were strongly associated with subsequent risk of hospitalisation with dementia, particularly in middle-aged individuals. Our results emphasise the importance of early lifestyle modification and risk factor treatment to prevent dementia.

Genomic regions that influence plasma levels of inflammatory markers in hypertensive sibships.

We carried out univariate and bivariate linkage analyses to identify genomic regions that may influence plasma levels of C-reactive protein (CRP) and fibrinogen and exert pleiotropic effects on both traits. Subjects included African American (AA, n=1310, mean age 62.7+/-9.4 years) and non-Hispanic white (NHW, n=796, mean age 58.4+/-9.8 years) belonging to hypertensive sibships. Plasma CRP was measured by an immunoturbidimetric assay and fibrinogen by the Clauss method. Genotyping was performed at 366 microsatellite marker loci spaced approximately 10 cM apart across the 22 autosomes. Estimation of heritability and linkage analyses was carried out using a variance components approach. Significant heritability was noted for CRP (0.38 in AA and 0.37 in NHW subjects) and fibrinogen (0.44 in AA and 0.28 in NHW subjects). Significant genetic correlation between CRP and fibrinogen was present in both AA (0.39) and NHW (0.40) subjects. In univariate linkage analysis, the maximum logarithm of odds (LOD) score for CRP was on chromosome 10q22 in NHW (LOD=1.69, 106.75 cM, P=0.0026) and for fibrinogen on chromosome 2 in AA (LOD=2.14, 55.5 cM, P=0.0009) subjects. Bivariate linkage analysis demonstrated suggestive evidence of linkage (defined as LOD score >or= 2.87) for both traits on chromosome 12 (LOD=3.44, 152.16 cM, P=0.0003) in AA and on chromosome 21 (LOD=3.03, 13.05 cM, P=0.0008) in NHW subjects. Plasma CRP and fibrinogen levels are heritable and genetically correlated. Linkage analyses identified several chromosomal regions that may harbour genes influencing CRP and fibrinogen levels and exert pleiotropic effects on both traits.

Metabolomics and cognition in African American adults in midlife: the atherosclerosis risk in communities study.

Clinical studies have shown alterations in metabolic profiles when patients with mild cognitive impairment and Alzheimer's disease dementia were compared to cognitively normal subjects. Associations between 204 serum metabolites measured at baseline (1987-1989) and cognitive change were investigated in 1035 middle-aged community-dwelling African American participants in the biracial Atherosclerosis Risk in Communities (ARIC) Study. Cognition was evaluated using the Delayed Word Recall Test (DWRT; verbal memory), the Digit Symbol Substitution Test (DSST; processing speed) and the Word Fluency Test (WFT; verbal fluency) at visits 2 (1990-1992) and 4 (1996-1998). In addition, Cox regression was used to analyze the metabolites as predictors of incident hospitalized dementia between baseline and 2011. There were 141 cases among 1534 participants over a median 17.1-year follow-up period. After adjustment for established risk factors, one standard deviation increase in N-acetyl-1-methylhistidine was significantly associated with greater 6-year change in DWRT scores (ß=-0.66 words; P=3.65 × 10-4). Two metabolites (one unnamed and a long-chain omega-6 polyunsaturated fatty acid found in vegetable oils (docosapentaenoate (DPA, 22:5 n-6)) were significantly associated with less decline on the DSST (DPA: ß=1.25 digit-symbol pairs, P=9.47 × 10-5). Two unnamed compounds and three sex steroid hormones were associated with an increased risk of dementia (all P<3.9 × 10-4). The association of 4-androstene-3beta, 17beta-diol disulfate 1 with dementia was replicated in European Americans. These results demonstrate that screening the metabolome in midlife can detect biologically plausible biomarkers that may improve risk stratification for cognitive impairment at older ages.

Cardiovascular risk factors and cognitive decline in middle-aged adults.

OBJECTIVE: To perform serial neuropsychological assessments to detect vascular risk factors for cognitive decline in the Atherosclerosis Risk in Communities cohort, a large biracial, multisite, longitudinal investigation of initially middle-aged individuals. METHODS: The authors administered cognitive assessments to 10,963 individuals (8,729 white individuals and 2,234 black individuals) on two occasions separated by 6 years. Subjects ranged in age at the first assessment from 47 to 70 years. The cognitive assessments included the delayed word recall (DWR) test, a 10-word delayed free recall task in which the learning phase included sentence generation with the study words, the digit symbol subtest (DSS) of the Wechsler Adult Intelligence Scale-Revised and the first-letter word fluency (WF) test using letters F, A, and S. RESULTS: In multivariate analyses (controlling for demographic factors), the presence of diabetes at baseline was associated with greater decline in scores on both the DSS and WF (p < 0.05), and the presence of hypertension at baseline was associated with greater decline on the DSS alone (p < 0.05). The association of diabetes with cognitive decline persisted when analysis was restricted to the 47- to 57-year-old subgroup. Smoking status, carotid intima-media wall thickness, and hyperlipidemia at baseline were not associated with change in cognitive test scores. CONCLUSIONS: Hypertension and diabetes mellitus were positively associated with cognitive decline over 6 years in this late middle-aged population. Interventions aimed at hypertension or diabetes that begin before age 60 might lessen the burden of cognitive impairment in later life.

Efficacy of behavioral management and patient education on vascular access cleansing compliance in hemodialysis patients.

Compared four treatment conditions to test their ability to enhance compliance with vascular access cleansing (VAC) procedures in a group of 56 hemodialysis patients. The conditions were patient education, behavioral management with monetary incentive, patient education/behavioral management, and attention control. Behavioral observers rated VAC behavior at pretreatment, posttreatment 1-month follow-up, and 1-year follow-up. Knowledge of VAC procedures was also assessed via a questionnaire at pretreatment and posttreatment. Data were analyzed using repeated-measures multivariate analyses of variance. Results indicated that the patients in the education/behavioral, behavioral, and education groups gave significantly more correct answers on our VAC knowledge questionnaires at posttreatment than did patients in the attention control group. Further, patients in the education/behavioral and behavioral groups completed significantly more VAC steps at posttreatment and 1-month follow-up than did patients in the education group and in the attention control group. Differences were not maintained at 1-year follow-up, although more than 50% of the patients were lost to follow-up. Implications of the present findings for behavioral and educational interventions are discussed.

Stress, coping, and well-being among third-year medical students.

BACKGROUND: Medical school is recognized as a stressful environment that often exerts a negative effect on the academic performance, physical health, and psychological well-being of the student. METHOD: Stress, coping, depression, and somatic distress were examined among 69 third-year students completing a psychiatry clerkship in 1992-93 at the University of Mississippi School of Medicine. Stress was assessed using the Medical Education Hassles Scale-R. Coping was assessed using the Coping Strategies Inventory. Depression was assessed using the Center for Epidemiologic Studies-Depression Scale, and somatic distress was assessed using the Wahler Physical Symptoms Inventory. Statistical methods included correlational analysis and hierarchical regression. RESULTS: Clinical levels of depression were found in 16 (23%) of the students, and 39 (57%) endorsed high levels of somatic distress. Stress accounted for a large percentage of the distress variance (i.e., 29% to 50%). Coping efforts contributed significant variance to the prediction of distress above and beyond that accounted for by stress alone, especially in relation to depression. Coping efforts classified by Engagement strategies were associated with fever depressive symptoms, while coping efforts classified by Disengagement strategies were associated with higher levels of depressive symptoms. CONCLUSIONS: Because students who employed coping efforts characterized by Engagement strategies suffered from fewer depressive symptoms, the results suggest that training in these types of strategies may be a useful intervention to lessen the negative consequences of stress among medical students.

Contingent social reinforcement for fluid compliance in a hemodialysis patient.

Two approaches, (a) patient education and (b) compliance-contingent social reinforcement, were employed to improve compliance with fluid restrictions in a chronically noncompliant hemodialysis patient of borderline intellectual functioning. Results indicated that only social reinforcement led to improved compliance (i.e., decreased intersession weight gain). Treatment effects were well maintained at both 3- and 6-month follow-ups. Contingency management strategies are recommended as a potentially cost effective treatment for noncompliance in hemodialysis patients.

PROTOTYPES: an urban model program of treatment and recovery services for dually diagnosed perinatal program participants.

PROTOTYPES, a women's treatment program located in Los Angeles, is described in terms of its services for pregnant and parenting women with coexisting substance abuse and mental health disorders. The philosophy of treatment, goals and objectives, treatment planning process, and treatment content are discussed. Management of the milieu, relational model considerations and staff self-care issues are presented in addition to future directions in treatment and research on women with coexisting disorders.

Organo-selenium-containing dental sealant inhibits bacterial biofilm.

Oral bacteria, including Streptococcus mutans and Streptococcus salivarius, contribute to tooth decay and plaque formation; therefore, it is essential to develop strategies to prevent dental caries and plaque formation. We recently showed that organo-selenium compounds covalently attached to different biomaterials inhibited bacterial biofilms. Our current study investigates the efficacy of an organo-selenium dental sealant (SeLECT-Defense(TM) sealant) in inhibiting S. mutans and S. salivarius biofilm formation in vitro. The organo-selenium was synthesized and covalently attached to dental sealant material via standard polymer chemistry. By colony-forming unit (CFU) assay and confocal microscopy, SeLECT-Defense(TM) sealant was found to completely inhibit the development of S. mutans and S. salivarius biofilms. To assess the durability of the anti-biofilm effect, we soaked the SeLECT-Defense(TM) sealant in PBS for 2 mos at 37°C and found that the biofilm-inhibitory effect was not diminished after soaking. To determine if organo-selenium inhibits bacterial growth under the sealant, we placed SeLECT-Defense sealant over a lawn of S. mutans. In contrast to a control sealant, SeLECT-Defense(TM) sealant completely inhibited the growth of S. mutans. These results suggest that the inhibitory effect of SeLECT-Defense(TM) sealant against S. mutans and S. salivarius biofilms is very effective and durable.

Cognitive decline and oral health in middle-aged adults in the ARIC study.

Even before dementia becomes apparent, cognitive decline may contribute to deterioration in oral health. This cohort study of middle-aged adults evaluated associations of six-year change in cognitive function with oral health behaviors and conditions in the Atherosclerosis Risk in Communities (ARIC) study. Cognitive function was measured at study visits in 1990-1992 and 1996-1998 with three tests: (a) Delayed Word Recall (DWR), (b) Digit Symbol Substitution (DSS), and (c) Word Fluency (WF). Cognitive decline scores were computed as 'studentized' residuals of 1996-1998 scores regressed against 1990-1992 scores. In 1996-1998, 10,050 participants answered dental screening questions, and 5,878 of 8,782 dentate participants received a comprehensive oral examination. Multiple regression models used cognitive change to predict oral health behaviors and conditions with adjustment for covariates. In the fully adjusted models, greater decline in all three measures of cognitive function was associated with increased odds of complete tooth loss. Greater decline in DSS and WF scores was associated with infrequent toothbrushing. Decline in WF scores was also associated with higher plaque levels. In these middle-aged adults, six-year cognitive decline was modestly associated with less frequent toothbrushing, plaque deposit, and greater odds of edentulism, but not with other oral behaviors or diseases.

Risk factors for lacune subtypes in the Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: Lacunar infarctions are mainly due to 2 microvascular pathologies: lipohyalinosis and microatheroma. Little is known about risk factor differences for these subtypes. We hypothesized that diabetes and glycated hemoglobin (HbA(1)c) would be related preferentially to the lipohyalinotic subtype. METHODS: We performed a cross-section analysis of the brain MRI data from 1,827 participants in the Atherosclerosis Risk in Communities study. We divided subcortical lesions ≤ 20 mm in diameter into those ≤ 7 mm (of probable lipohyalinotic etiology) and 8-20 mm (probably due to microatheroma) and used Poisson regression to investigate associations with the number of each type of lesion. Unlike previous studies, we also fitted a model involving lesions <3 mm. RESULTS: Age (prevalence ratio [PR] 1.11 per year; 95% confidence interval [CI] 1.08-1.14), black ethnicity (vs white, PR 1.66; 95% CI 1.27-2.16), hypertension (PR 2.12; 95% CI 1.61-2.79), diabetes (PR 1.42; 95% CI 1.08-1.87), and ever-smoking (PR 1.34; 95% CI 1.04-1.74) were significantly associated with lesions ≤ 7 mm. Findings were similar for lesions <3 mm. HbA(1)c, substituted for diabetes, was also associated with smaller lesions. Significantly associated with 8-20 mm lesions were age (PR 1.14; 95% CI 1.09-1.20), hypertension (PR 1.79; 95% CI 1.14-2.83), ever-smoking (PR 2.66; 95% CI 1.63-4.34), and low-density lipoprotein (LDL) cholesterol (PR 1.27 per SD; 95% CI 1.06-1.52). When we analyzed only participants with lesions, history of smoking (PR 1.99; 95% CI 1.23-3.20) and LDL (PR 1.33 per SD; 95% CI 1.08-1.65) were associated with lesions 8-20 mm. CONCLUSIONS: Smaller lacunes (even those <3 mm) were associated with diabetes and HbA(1)c, and larger lacunes associated with LDL cholesterol, differences which support long-held theories relating to their underlying pathology. The findings may contribute to broader understanding of cerebral microvascular disease.

Plasma C-terminal pro-endothelin-1 is associated with left ventricular mass index and aortic root diameter in African-American adults with hypertension.

Endothelin-1 (ET-1), a circulating vasoactive peptide with potent vasoconstricting and mitogenic properties, may contribute to target-organ damage in hypertension. We investigated whether plasma levels of C-terminal pro-endothelin-1 (CT-pro-ET-1) are associated with left ventricular (LV) mass and aortic root diameter in African-American adults with hypertension. Plasma CT-pro-ET-1 was measured by an immunoluminometric assay in 1041 African Americans (65±9 years, 72% women) with hypertension. LV mass and aortic root diameter were measured according to the American Society of Echocardiography guidelines, and LV mass was indexed by height to the power 2.7 (LVMi). Multivariable regression analyses were used to assess whether plasma CT-pro-ET-1 was associated with LVMi and aortic root diameter, independent of potential confounding variables. Plasma CT-pro-ET-1 was modestly correlated with LVMi (r=0.21, P<0.0001) and aortic root diameter (r=0.09, P=0.004). In separate multivariable regression models that adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, smoking history, diabetes, history of myocardial infarction or stroke, and blood pressure-lowering medication and statin use, log CT-pro-ET-1 was significantly associated with greater LVMi (P=0.001) and larger aortic root diameter (P=0.006). CT-pro-ET-1 is independently associated with LVMi and aortic root diameter and may be a marker of target-organ damage in African-Americans adults with hypertension.