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Using data from the Health, Aging, and Body Composition study, we examined whether low 25-hydroxyvitamin D (25[OH]D) concentrations were associated with prevalent or incident cognitive impairment. Serum 25(OH)D concentrations were measured in 2,786 older adults and categorized as 1.5 standard deviations below race and education specific means on either digit symbol substitution test or modified mini-mental state test. Logistic regression determined the odds of cognitive impairment at baseline and year 5 by 25(OH)D category. 25(OH)D concentrations were

Previous studies have shown that more active older adults have better cognition and brain health based on a variety of structural neuroimaging measures. Nevertheless, the effects of maintaining physical activity (PA) over an extended period of time on future changes in older adults' cognition and brain structure are unknown. Participants were 141 initially well-functioning community-dwelling older adults (aged 70-79 years at baseline; 60% female; 42% black) studied over a 13-year period. PA (self-reported time spent walking) was assessed annually from years 1 to 10. Magnetic resonance imaging with diffusion tensor was performed at years 10 and 13. Time spent walking decreased on average by 8.4% annually from year 1 to year 10. Independent of initial time spent walking, demographics, and APOE e4 status, better maintenance of time spent walking over the decade predicted less reduction in hippocampal volume (p = 0.03), smaller increases in global gray matter mean diffusivity and white matter axial diffusivity (p < 0.01), and maintenance of general cognitive performance (p < 0.01). Maintenance of cognitive performance was associated with smaller increases in white matter axial diffusivity (p < 0.01). PA at baseline and at year 10, as well as changes in PA over a 5-year period, was less predictive of future changes in brain structure and cognition. Thus, how PA levels change over longer periods of aging may be an important contributor to cognitive and neural protection.

ObjectiveThe objective of the study is was investigate the association between hearing impairment and anxiety.MethodWe conducted a cross-sectional analysis of 1,732 community-based adults aged 76 to 85 years who participated in the Health Aging and Body Composition (ABC) study. Logistic regression models were adjusted for demographic and cardiovascular risk factors. Hearing impairment was defined by the speech-frequency pure tone average. Anxiety was defined as reporting two symptoms of at least "a little" or one symptom "quite a bit" on the three-item Hopkins Symptom Checklist.ResultsCompared with individuals with no hearing impairment, the odds of prevalent anxiety were higher among individuals with mild hearing impairment (odds ratio [OR] = 1.32, 95% confidence interval [CI] = [1.01, 1.73]) and moderate or greater hearing impairment (OR = 1.59, 95% CI = [1.14, 2.22]). Hearing aid use was not significantly associated with lower odds of anxiety.DiscussionHearing impairment is independently associated with greater odds of anxiety symptoms in older adults.

BackgroundFew cohort studies have examined longitudinal associations between age-related changes in cognition and physical performance. Further, whether these associations differ for men versus women or can be attributed to differences in physical activity (PA) is unknown.MethodsParticipants were 2,876 initially well-functioning community-dwelling older adults (aged 70-79 years at baseline; 52% female; 39% black) studied over a 9-year period. Usual gait speed, self-reported PA, and two cognitive measures-Digit Symbol Substitution Test (DSST) and Mini-Modified Mental State examination (3MS)-were assessed years 0 (ie, baseline), 4, and 9.ResultsEarly decline between years 0 and 4 in gait speed predicted later decline between years 4 and 9 in performance on the 3MS (β = 0.10, p = .004) and on the DSST (β = 0.16, p < .001). In contrast, the associations between early decline in cognition and later decline in gait speed were weaker and were non-significant after correcting for multiple comparisons (β = 0.08, p = .019 for 3MS and β = .06, p = .051 for DSST). All associations were similar for women and men and were unaltered when accounting for PA levels.ConclusionsThe results indicate declining gait speed as a precursor to declining cognitive functioning, and suggest a weaker reciprocal process among older women and men.

BackgroundFew studies have compared the risk of recurrent falls across various antidepressant agents-using detailed dosage and duration data-among community-dwelling older adults, including those who have a history of a fall/fracture.ObjectiveTo examine the association of antidepressant use with recurrent falls, including among those with a history of falls/fractures, in community-dwelling elders.MethodsThis was a longitudinal analysis of 2948 participants with data collected via interview at year 1 from the Health, Aging and Body Composition study and followed through year 7 (1997-2004). Any antidepressant medication use was self-reported at years 1, 2, 3, 5, and 6 and further categorized as (1) selective serotonin reuptake inhibitors (SSRIs), (2) tricyclic antidepressants, and (3) others. Dosage and duration were examined. The outcome was recurrent falls (≥2) in the ensuing 12-month period following each medication data collection.ResultsUsing multivariable generalized estimating equations models, we observed a 48% greater likelihood of recurrent falls in antidepressant users compared with nonusers (adjusted odds ratio [AOR] = 1.48; 95% CI = 1.12-1.96). Increased likelihood was also found among those taking SSRIs (AOR = 1.62; 95% CI = 1.15-2.28), with short duration of use (AOR = 1.47; 95% CI = 1.04-2.00), and taking moderate dosages (AOR = 1.59; 95% CI = 1.15-2.18), all compared with no antidepressant use. Stratified analysis revealed an increased likelihood among users with a baseline history of falls/fractures compared with nonusers (AOR = 1.83; 95% CI = 1.28-2.63).ConclusionAntidepressant use overall, SSRI use, short duration of use, and moderate dosage were associated with recurrent falls. Those with a history of falls/fractures also had an increased likelihood of recurrent falls.

ImportanceDepression has been identified as a risk factor for dementia. However, most studies have measured depressive symptoms at only one time point, and older adults may show different patterns of depressive symptoms over time.ObjectiveTo investigate the association between trajectories of depressive symptoms and risk of dementia in older adults.Design, setting, and participantsThis was a prospective cohort investigation of black and white community-dwelling older adults in the Health, Aging, and Body Composition study. Participants were enrolled between May 1997 and June 1998 and followed up through 2001-2002. The dates of this analysis were September 2014 to December 2015. The setting was community research centers in Memphis, Tennessee, and Pittsburgh, Pennsylvania. Trajectories of depressive symptoms were assessed from baseline to year 5. Symptoms were measured with the Center for Epidemiologic Studies Depression Scale Short Form, and trajectories were calculated using latent class growth curve analysis.Main outcomes and measuresIncident dementia through year 11, determined by dementia medication use, hospital records, or significant cognitive decline (≥1.5 SD race-specific decline on the Modified Mini-Mental State Examination). We examined the association between depressive symptom trajectories and dementia incidence using Cox proportional hazards regression models adjusted for demographics, health factors that differed between groups, and cognition during the depressive symptom assessment period (baseline to year 5).ResultsThe analytic cohort included 2488 black and white older adults with repeated depressive symptom assessments from baseline to year 5 who were free of dementia throughout that period. Their mean (SD) age at baseline was 74.0 (2.8) years, and 53.1% (n = 1322) were female. The following 3 depressive symptom trajectories were identified: consistently minimal symptoms (62.0% [n = 1542] of participants), moderate and increasing symptoms (32.2% [n = 801] of participants), and high and increasing symptoms (5.8% [n = 145] of participants). Compared with the consistently minimal trajectory, having a high and increasing depressive symptom trajectory was associated with significantly increased risk of dementia (fully adjusted hazard ratio, 1.94; 95% CI, 1.30-2.90), while the moderate and increasing trajectory was not associated with risk of dementia after full adjustment. Sensitivity analyses indicated that the high and increasing trajectory was associated with dementia incidence, while depressive symptoms at individual time points were not.Conclusions and relevanceOlder adults with a longitudinal pattern of high and increasing depressive symptoms are at high risk for dementia. Individuals' trajectory of depressive symptoms may inform dementia risk more accurately than one-time assessment of depressive symptoms.

ObjectivesTo better understand the potential impact of hearing impairment (HI) and hearing aid use on emotional vitality and mental health in older adults.MethodWe investigated the cross-sectional association of HI with emotional vitality in 1,903 adults aged 76-85 years in the Health ABC study adjusted for demographic and cardiovascular risk factors. Hearing was defined by the speech frequency pure tone average (no impairment < 25 dB, mild impairment 25-40 dB, and moderate or greater impairment > 40 dB). Emotional vitality was defined as having a high sense of personal mastery, happiness, low depressive symptomatology, and low anxiety.ResultsCompared with individuals with no HI, participants with moderate or greater HI had a 23% lower odds of emotional vitality (odds ratio [OR] = 0.77; 95% confidence interval [CI]: 0.59-0.99). Hearing aid use was not associated with better emotional vitality (OR = 0.98; 95% CI: 0.81-1.20).DiscussionHI is associated with lower odds of emotional vitality in older adults. Further studies are needed to examine the longitudinal impact of HI on mental health and well-being.

BackgroundDepression and disability are closely linked. Less is known regarding clinical and subclinical depressive symptoms over time and risk of disability and mortality.MethodsResponses to the Center for Epidemiologic Studies Short Depression scale (CES-D10) were assessed over a 4-year period in men (n = 1032) and women (n = 1070) aged 70-79 years initially free from disability. Depressive symptom trajectories were defined with group-based models. Disability (2 consecutive reports of severe difficulty walking one-quarter mile or climbing 10 steps) and mortality were determined for 9 subsequent years. Hazard ratios (HRs) were estimated using Cox proportional hazards adjusted for covariates.ResultsThree trajectories were identified: persistently nondepressed (54% of men, 54% of women, mean baseline CES-D10: 1.16 and 1.46), mildly depressed and increasing (40% of men, 38% of women, mean baseline CES-D10: 3.60 and 4.35), and depressed and increasing (6% of men, 8% of women, mean baseline CES-D10: 7.44 and 9.61). Disability and mortality rates per 1,000 person years were 41.4 and 60.3 in men and 45.8 and 41.9 in women. Relative to nondepressed, men in the mildly depressed (HR = 1.45, 95% confidence interval [CI] 1.11-1.89) and depressed trajectories (HR = 2.12, 95% CI 1.33-3.38) had increased disability; women in the depressed trajectory had increased disability (HR = 2.02, 95% CI 1.37-2.96). Men in the mildly depressed (HR = 1.24, 95% CI 1.01-1.52) and depressed trajectories (HR = 1.63, 95% CI 1.10-2.41) had elevated mortality risk; women exhibited no mortality risk.ConclusionsTrajectories of depressive symptoms without recovery may predict disability and mortality in apparently healthy older populations, thus underscoring the importance of monitoring depressive symptoms in geriatric care.

BackgroundInflammation, slow gait, and depression individually are associated with mortality, yet little is known about the trajectories of these measures, their interrelationships, or their collective impact on mortality.MethodsLongitudinal latent class analysis was used to evaluate trajectories of depression (Center for Epidemiologic Studies Depression ≥ 10), slow gait ( 3.2 pg/mL) using data from the Health Aging and Body Composition Study. Logistic regression was used to identify their associations with mortality.ResultsFor each outcome, low-probability (n inflammation = 1,656, n slow gait = 1,471, n depression = 1,458), increasing-probability (n inflammation = 847, n slow gait = 880, n depression = 1,062), and consistently high-probability (n inflammation = 572, n slow gait = 724, n depression = 555) trajectories were identified, with 22% of all participants classified as having increasing or consistently high-probability trajectories on inflammation, slow gait, and depression (meaning probability of impairment on each outcome increased from low to moderate/high or remained high over 10 years). Trajectories of slow gait were associated with inflammation (r = .40, p < .001) and depression (r = .49, p < .001). Although worsening trajectories of inflammation were independently associated with mortality (p < .001), the association between worsening trajectories of slow gait and mortality was only present in participants with worsening depression trajectories (p < .01). Participants with increasing/consistently high trajectories of depression and consistently high trajectories of inflammation and slow gait (n = 247) have an adjusted-morality rate of 85.2%, greater than all other classification permutations.ConclusionsComprehensive assessment of older adults is warranted for the development of treatment strategies targeting a high-mortality risk phenotype consisting of inflammation, depression, and slow gait speed.

BackgroundIdentifying factors associated with functional declines in older adults is important given the aging of the population. We investigated if hearing impairment is independently associated with objectively measured declines in physical functioning in a community-based sample of older adults.MethodsProspective observational study of 2,190 individuals from the Health, Aging, and Body Composition study. Participants were followed annually for up to 11 visits. Hearing was measured with pure-tone audiometry. Physical functioning and gait speed were measured with the Short Physical Performance Battery (SPPB). Incident disability and requirement for nursing care were assessed semiannually through self-report.ResultsIn a mixed-effects model, greater hearing impairment was associated with poorer physical functioning. At both Visit 1 and Visit 11, SPPB scores were lower in individuals with mild (10.14 [95% CI 10.04-10.25], p < .01; 7.35 [95% CI 7.12-7.58], p < .05) and moderate or greater hearing impairment (10.04 [95% CI 9.90-10.19], p < .01; 7.00 [95% CI 6.69-7.32], p < .01) than scores in normal hearing individuals (10.36 [95% CI 10.26-10.46]; 7.71 [95% CI 7.49-7.92]). We observed that women with moderate or greater hearing impairment had a 31% increased risk of incident disability (Hazard ratio [HR] =1.31 [95% CI 1.08-1.60], p < .01) and a 31% increased risk of incident nursing care requirement (HR = 1.31 [95% CI 1.05-1.62], p = .02) compared to women with normal hearing.ConclusionsHearing impairment is independently associated with poorer objective physical functioning in older adults, and a 31% increased risk for incident disability and need for nursing care in women.

ImportanceApolipoprotein E (APOE) ε4 is an established risk factor for cognitive decline and the development of dementia, but other factors may help to minimize its effects.ObjectiveUsing APOE ε4 as an indicator of high risk, we investigated factors associated with cognitive resilience among black and white older adults who are APOE ε4 carriers.Design, setting, and participantsParticipants included 2487 community-dwelling older (aged 69-80 years at baseline) black and white adults examined at 2 community clinics in the prospective cohort Health, Aging, and Body Composition (Health ABC) study. The baseline visits occurred from May 1997 through June 1998. Our primary analytic cohort consisted of 670 APOE ε4 carriers (329 black and 341 white participants) who were free of cognitive impairment at baseline and underwent repeated cognitive testing during an 11-year follow-up (through 2008) using the Modified Mini-Mental State Examination.Main outcomes and measuresWe stratified all analyses by race. Using the Modified Mini-Mental State Examination scores, we assessed normative cognitive change in the entire cohort (n = 2487) and classified the APOE ε4 carriers as being cognitively resilient vs nonresilient by comparing their cognitive trajectories with those of the entire cohort. We then conducted bivariate analyses and multivariable random forest and logistic regression analyses to explore factors predictive of cognitive resilience in APOE ε4 carriers.ResultsAmong white APOE ε4 carriers, the strongest predictors of cognitive resilience were, in relative order of importance, no recent negative life events, a higher literacy level, advanced age, a higher educational level, and more time spent reading. Among black APOE ε4 carriers, the strongest predictors of cognitive resilience were, in relative order of importance, a higher literacy level, a higher educational level, female sex, and the absence of diabetes mellitus. In follow-up logistic regression models, higher literacy level (adjusted odds ratio [OR], 9.50 [95% CI, 2.67-60.89]), a higher educational level (adjusted OR for college graduate vs less than high school, 3.81 [95% CI, 1.13-17.56]), and age (adjusted OR for 73-76 vs 69-72 years, 2.01 [95% CI, 1.13-3.63]) had significant independent effects in predicting cognitive resilience among white APOE ε4 carriers. Among black APOE ε4 carriers, a higher literacy level (adjusted OR, 2.27 [95% CI, 1.29-4.06]) and a higher educational level (adjusted OR for high school graduate/some college vs less than high school, 2.86 [95% CI, 1.54-5.49]; adjusted OR for college graduate vs less than high school, 2.52 [95% CI, 1.14-5.62]) had significant independent effects in predicting cognitive resilience.Conclusions and relevanceAlthough APOE ε4 carriers are at high risk for cognitive decline, our findings suggest possible intervention targets, including the enhancement of cognitive reserve and improvement of other psychosocial and health factors, to promote cognitive resilience among black and white APOE ε4 carriers.

BackgroundResults from numerous studies suggest protective effects of the Mediterranean diet for cardiovascular disease, cancer, and mortality. Evidence for an association with a decreased risk of cognitive decline is less consistent and studies are limited by a lack of diversity in their populations.MethodsWe followed 2,326 older adults (38.2% black, 51.3% female, aged 70-79 at baseline) over 8 years in a prospective cohort study in the United States (Health, Aging and Body Composition study). To measure adherence to a Mediterranean diet, we calculated race-specific tertiles of the MedDiet score (range: 0-55) using baseline food frequency questionnaires. Cognitive decline was assessed using repeated Modified Mini Mental State Examination scores over the study. We used linear mixed models to assess the association between MedDiet score and trajectory of cognitive decline.ResultsAmong blacks, participants with high MedDiet scores had a significantly lower mean rate of decline on the Modified Mini Mental State Examination score compared with participants with lower MedDiet scores (middle and bottom tertiles). The mean difference in points per year was 0.22 (95% confidence interval: 0.05-0.39; p = .01) after adjustment for age, sex, education, body mass index, current smoking, physical activity, depression, diabetes, total energy intake, and socioeconomic status. No association between MedDiet scores and change in Modified Mini Mental State Examination score was seen among white participants (p = .14).ConclusionsStronger adherence to the Mediterranean diet may reduce the rate of cognitive decline among black, but not white older adults. Further studies in diverse populations are needed to confirm this association and pinpoint mechanisms that may explain these results.

We aimed to examine trajectories of inflammatory markers and cognitive decline over 10 years. Cox proportional hazards models were used to examine the association between interleukin-6 and C-reactive protein (CRP) trajectory components (slope, variability, and baseline level) and cognitive decline among 1323 adults, aged 70-79 years in the Health, Aging, and Body Composition Study. We tested for interactions by sex and apolipoprotein E (APOE) genotype. In models adjusted for multiple covariates and comorbidities, extreme CRP variability was significantly associated with cognitive decline (hazard ratio [HR] 1.6, 95% confidence interval [CI]: 1.1-2.3). This association was modified by sex and APOE e4 (p < 0.001 for both), such that the association remained among women (HR = 1.8; 95% CI: 1.1, 3.0) and among those with no APOE e4 allele (HR = 1.6; 95% CI: 1.1, 2.5). There were no significant associations between slope or baseline level of CRP and cognitive decline nor between interleukin-6 and cognitive decline. We believe CRP variability likely reflects poor control of or greater changes in vascular or metabolic disease over time, which in turn is associated with cognitive decline.

ObjectivesTo evaluate race-related differences in depression onset and recovery in older persons, overall and by sex, and examine race-related differences in mortality according to depression.DesignProspective cohort study.SettingGeneral community in pre-designated zip code areas in Memphis, Tennessee, and Pittsburgh, Pennsylvania.Participants3,075 persons aged 70-79 years at baseline in the Health, Aging, and Body Composition study.MeasurementsDepression was assessed at eight time points over 10 years using the 10-item Center for Epidemiologic Studies-Depression scale; patients were categorized as nondepressed (score less than 8) or depressed (score of 8 or higher). We created variables for transitions across each 18-month time interval, namely, from nondepressed or depressed to nondepressed, depressed, or death, and determined the association between race and the average likelihood of these transitions over time.ResultsA higher percentage of blacks than whites were depressed at nearly all time points. Adjusting for demographics, common chronic conditions, and body mass index, blacks had a higher likelihood of experiencing depression onset than whites (odds ratio [OR]: 1.22; 95% confidence interval [CI]: 1.03-1.43); among men, blacks were more likely to experience depression onset than whites (OR: 1.44; 95% CI: 1.24-2.89). Blacks also had a higher likelihood of transitioning from nondepressed to death (OR: 1.79; 95% CI: 1.30-2.46). Overall and in sex-stratified analyses, race was not associated with recovery from depression or with the transition from depression to death.ConclusionOur findings highlight race differences in depression in older persons and encourage further research on the course of depression in older black patients.

BackgroundLow literacy is common among the elderly and possibly more reflective of educational attainment than years of school completed. We examined the association between literacy and risk of likely dementia in older adults.MethodsParticipants were 2,458 black and white elders (aged 71-82) from the Health, Aging and Body Composition study, who completed the Rapid Estimate of Adult Literacy in Medicine and were followed for 8 years. Participants were free of dementia at baseline; incidence of likely dementia was defined by hospital records, prescription for dementia medication, or decline in Modified Mini-Mental State Examination score. We conducted Cox proportional hazard models to evaluate the association between literacy and incidence of likely dementia. Demographics, education, income, comorbidities, lifestyle variables, and apolipoprotein E (APOE) ε4 status were included in adjusted analyses.ResultsTwenty-three percent of participants had limited literacy (

ObjectivesTo examine the relationship between 25-hydroxyvitamin D (25(OH)D) levels and cognitive performance over time in older adults in the Health, Aging and Body Composition (Health ABC) Study.DesignProspective cohort study.SettingCommunity-dwelling participants in Pittsburgh, Pennsylvania, and Memphis, Tennessee.ParticipantsWell-functioning adults aged 70 to 79 at baseline with serum 25(OH)D measured at the 12-month follow-up visit and cognitive function measured at baseline and 4-year follow-up visit (N = 2,777).MeasurementsVitamin D status was categorized as 25(OH)D levels of less than 20.0 ng/mL, 20.0 to 29.9 ng/mL, or 30.0 ng/mL or greater. Cognition was measured using the modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST). Linear regression models adjusting for multiple covariates, including age, education, sex, race, site, season, physical activity, and comorbidities, were used in the analysis.ResultsSixty-eight percent of participants had 25(OH)D levels of less than 30.0 ng/mL. Lower 25(OH)D levels were associated with lower baseline cognitive scores on the 3MS (adjusted mean 89.9, 95% confidence interval (CI) = 89.4-90.4 for

Plasma amyloid β-42 (Aβ42) and Aβ42/Aβ40 are increasingly recognized as biomarkers for dementia, with low levels indicating increased risk. Little is known about the demographic and medical correlates of plasma Aβ40 or Aβ42. In 997 community-dwelling, nondemented older adults from the Health, Aging, and Body Composition Study, we determined the cross-sectional association between a wide range of demographic and medical variables with Aβ40 and Aβ42. In multivariate stepwise linear regression models, Aβ40 was significantly associated with race (β=-14.70, F=22.01, P

BACKGROUND Whether hearing loss is independently associated with accelerated cognitive decline in older adults is unknown. METHODS We studied 1984 older adults (mean age, 77.4 years) enrolled in the Health ABC Study, a prospective observational study begun in 1997-1998. Our baseline cohort consisted of participants without prevalent cognitive impairment (Modified Mini-Mental State Examination [3MS] score, ≥80) who underwent audiometric testing in year 5. Participants were followed up for 6 years. Hearing was defined at baseline using a pure-tone average of thresholds at 0.5 to 4 kHz in the better-hearing ear. Cognitive testing was performed in years 5, 8, 10, and 11 and consisted of the 3MS (measuring global function) and the Digit Symbol Substitution test (measuring executive function). Incident cognitive impairment was defined as a 3MS score of less than 80 or a decline in 3MS score of more than 5 points from baseline. Mixed-effects regression and Cox proportional hazards regression models were adjusted for demographic and cardiovascular risk factors. RESULTS In total, 1162 individuals with baseline hearing loss (pure-tone average >25 dB) had annual rates of decline in 3MS and Digit Symbol Substitution test scores that were 41% and 32% greater, respectively, than those among individuals with normal hearing. On the 3MS, the annual score changes were -0.65 (95% CI, -0.73 to -0.56) vs -0.46 (95% CI, -0.55 to -0.36) points per year (P = .004). On the Digit Symbol Substitution test, the annual score changes were -0.83 (95% CI, -0.94 to -0.73) vs -0.63 (95% CI, -0.75 to -0.51) points per year (P = .02). Compared to those with normal hearing, individuals with hearing loss at baseline had a 24% (hazard ratio, 1.24; 95% CI, 1.05-1.48) increased risk for incident cognitive impairment. Rates of cognitive decline and the risk for incident cognitive impairment were linearly associated with the severity of an individual's baseline hearing loss. CONCLUSIONS Hearing loss is independently associated with accelerated cognitive decline and incident cognitive impairment in community-dwelling older adults. Further studies are needed to investigate what the mechanistic basis of this association is and whether hearing rehabilitative interventions could affect cognitive decline.

BackgroundOlder adults with depression have an increased risk of developing dementia. Low plasma beta-amyloid 42 (Aβ42) and Aβ42/Aβ40 have emerged as promising biomarkers of dementia. The association between depression and plasma Aβ is unclear.MethodsIn this longitudinal study of 988 community-dwelling elders from the Health Aging and Body Composition study, depression was assessed with the Center for Epidemiologic Studies-Depression Scale 10-item version. We determined the association between Aβ42 and Aβ42/Aβ40 tertile and depression at baseline and over 9 years. We also stratified the models to determine if apolipoprotein E e4 allele status modified the associations.ResultsMean baseline age was 74.0 ± 3.0 years, 51 (5.2%) participants had depression, 545 (55.2%) were women, 531 (53.7%) were black, and 286 (30.7%) had one or more apolipoprotein E e4 allele. At baseline, there was no association between Aβ42/Aβ40 or Aβ42 and depression. Over 9 years, 220 (23.5%) participants developed depression. In adjusted Cox proportional hazards models, among those with one or more e4 allele, low Aβ42/Aβ40 was associated with an increased risk of developing depression over time (low 10.8% vs high 3.2%, hazard ratio = 2.38, 95% confidence interval: 1.15-4.92). Among those with no e4 allele, there was no association between Aβ42/Aβ40 and risk of depression over time (13.3% vs 17.5%, hazard ratio = 0.80, 95% confidence interval: 0.52-1.23; p value for interaction = .003).ConclusionsThe association between low plasma Aβ42/Aβ40 and increased risk of incident depression among those with one or more apolipoprotein E e4 allele implies a synergistic relationship similar to that found with dementia. Future work should investigate the interrelationships among plasma Aβ42/Aβ40, depression, and dementia.

BACKGROUND Leukocyte telomere length (LTL) is an emerging marker of biological age. Chronic inflammatory activity is commonly proposed as a promoter of biological aging in general, and of leukocyte telomere shortening in particular. In addition, senescent cells with critically short telomeres produce pro-inflammatory factors. However, in spite of the proposed causal links between inflammatory activity and LTL, there is little clinical evidence in support of their covariation and interaction. METHODOLOGY/PRINCIPAL FINDINGS To address this issue, we examined if individuals with high levels of the systemic inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) had increased odds for short LTL. Our sample included 1,962 high-functioning adults who participated in the Health, Aging and Body Composition Study (age range: 70–79 years). Logistic regression analyses indicated that individuals with high levels of either IL-6 or TNF-α had significantly higher odds for short LTL. Furthermore, individuals with high levels of both IL-6 and TNF-α had significantly higher odds for short LTL compared with those who had neither high (OR = 0.52, CI = 0.37–0.72), only IL-6 high (OR = 0.57, CI = 0.39–0.83) or only TNF-α high (OR = 0.67, CI = 0.46–0.99), adjusting for a wide variety of established risk factors and potential confounds. In contrast, CRP was not associated with LTL.BACKGROUND Leukocyte telomere length (LTL) is an emerging marker of biological age. Chronic inflammatory activity is commonly proposed as a promoter of biological aging in general, and of leukocyte telomere shortening in particular. In addition, senescent cells with critically short telomeres produce pro-inflammatory factors. However, in spite of the proposed causal links between inflammatory activity and LTL, there is little clinical evidence in support of their covariation and interaction. METHODOLOGY/PRINCIPAL FINDINGS To address this issue, we examined if individuals with high levels of the systemic inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) had increased odds for short LTL. Our sample included 1,962 high-functioning adults who participated in the Health, Aging and Body Composition Study (age range: 70–79 years). Logistic regression analyses indicated that individuals with high levels of either IL-6 or TNF-α had significantly higher odds for short LTL. Furthermore, individuals with high levels of both IL-6 and TNF-α had significantly higher odds for short LTL compared with those who had neither high (OR = 0.52, CI = 0.37–0.72), only IL-6 high (OR = 0.57, CI = 0.39–0.83) or only TNF-α high (OR = 0.67, CI = 0.46–0.99), adjusting for a wide variety of established risk factors and potential confounds. In contrast, CRP was not associated with LTL. CONCLUSIONS Results suggest that cumulative inflammatory load, as indexed by the combination of high levels of IL-6 and TNF-α, is associated with increased odds for short LTL. In contrast, high levels of CRP were not accompanied by short LTL in this cohort of older adults. These data provide the first large-scale demonstration of links between inflammatory markers and LTL in an older population.

BackgroundSlowing information processing is common among community-dwelling elderly and it predicts greater mortality and disability risk. Slowing information processing is related to brain macro-structural abnormalities. Specifically, greater global atrophy and greater small vessel disease of the white matter (WM) have been associated with slower processing speed. However, community-dwelling elderly with such macro-structural abnormalities can maintain processing speed. The roles of brain micro-structure for slow processing in very old adults living in the community is uncertain, as epidemiological studies relating these brain markers to cognition and in the context of other health characteristics are sparse.HypothesisInformation processing is cross-sectionally associated with WM micro-structure independent of overt macro-structural abnormalities and also independent of health related characteristics.MethodsImaging indices of micro-structure diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), macro-structure white matter hyperintensities (WMH), gray matter (GM) volume, digit symbol substitution test (DSST), and health characteristics were measured in 272 elderly (mean age 83 years old, 43% men, 40% black) living in the community.ResultsThe DTI- and MTI-indices of micro-structure from the normal appearing WM and not from the normal appearing GM were associated with DSST score independent of WMH and GM volumes. Associations were also independent of age, race, gender, mini-mental score, systolic blood pressure, and prevalent myocardial infarction.InterpretationDTI and MTI-indices of normal appearing WM are indicators of information processing speed in this cohort of very old adults living in the community. Since processing slowing is a potent index of mortality and disability, these indices may serve as biomarkers in prevention or treatment trials of disability.

Background. Increasingly, researchers have begun to explore pathways through which psychosocial factors might influence cardiovascular disease, with some emphasis on early markers. The current study examined the cross-sectional association between psychosocial factors and aortic pulse wave velocity (an early marker of cardiovascular disease) in a biracial cohort of older adults. We were particularly interested in determining whether the association between psychosocial factors and aortic pulse wave velocity differed for older blacks compared with whites. Methods. Participants were 2,488 (40% black and 52% female) older adults from the Health, Aging, and Body Composition Study. Carotid--femoral aortic pulse wave velocity was assessed using standard methodologies. Depressive symptoms, anxiety symptoms, negative life events, and inadequate emotional support were assessed, and a summary psychosocial risk index was created. Results. In multivariable linear regression models, psychosocial risk was not associated with aortic pulse wave velocity (Estimate [Est] = .00, p = .83), but there was a significant Race x Psychosocial risk interaction (Est = .07, p = .01), after adjusting for age, race, sex, and education. Further analyses revealed that this association was driven by the inadequate emotional support component of psychosocial risk (Race x Inadequate emotional support, p = .005). In race-stratified analyses, inadequate emotional support was associated with higher levels of arterial stiffness in older blacks (Est = .05, p = .04) but not whites (Est = -.04, p =. 13). This association persisted after adjusting for demographics, cardiovascular risk factors, and social network characteristics. Conclusions. Findings suggest that older blacks may be particularly vulnerable to the effects of inadequate emotional support on vascular health. Interventions aimed at increasing social support among this population might be beneficial in reducing cardiovascular disease risk. Key Words: Psychosocial--Social support--Arterial stiffness--Cardiovascular disease--African-Americans. doi: 10.1093/gerona/glq089

Background. The health pessimism hypothesis suggests that Black elders are more pessimistic about health than Whites and therefore tend to report lower self rated health (SRH) at comparable health status. The current analysis examined the factors associated with SRH and tested the health pessimism hypothesis among older adults at similar levels of physical functioning. Methods. The study example included 2,729 Health, Aging, and Body Composition study participants aged 70-79 years. We used hierarchical logistic regression to examine the association between race and SRH while adjusting for demographic, physical health, and psychosocial factors. The analyses were repeated for participants at similar levels of objective functioning to test the health pessimism hypothesis. Results. The association between race and SRH remained independent of physical and psychosocial health variables, with Whites being 3.7 times more likely than Black elders to report favorable SRH. This association was significant at each level of physical functioning and greater at the higher (odds ratio [OR] = 5.5) versus lower (OR = 2.2) levels of functioning. Conclusions. The results suggest greater health pessimism among Black elders and expand previous work by including objective functioning in multidimensional models to deconstruct race variations in the SRH of older adults. Key Words: Self-rated health Health pessimism--Objective measures--Physical functioning.

Background. This study examines the association between socioeconomic status (SES) and inflammatory markers in well-functioning older adults and seeks to determine whether any association remains after adjusting for biomedical and behavioral factors typically related to elevated serum levels of inflammatory markers. Methods. Data were obtained from 3044 men and women, aged 70-79 from Pittsburgh, Pennsylvania and Memphis, Tennessee participating in the Health, Aging and Body Composition study. Three indicators of SES were used: education, income, and ownership of financial assets. Serum levels of interleukin-6, C-reactive protein, and tumor necrosis factor-[alpha] were measured. Results. Low SES was associated with significantly elevated levels of interleukin-6, C-reactive protein, and tumor necrosis factor-[alpha] compared to high SES. Behavioral factors (including smoking, drinking, obesity) explained a substantial part of the inverse association between SES and inflammatory markers. Adjustment for prevalent diseases (including heart diseases, lung disease, and diabetes) associated with inflammation explained less of the association. Conclusions. This study suggests that interventions to improve health behaviors, even in old age and especially in low SES groups, may be useful in reducing risks associated with inflammation.