Cumulative Inflammatory Load Is Associated with Short Leukocyte Telomere Length in the Health, Aging and Body Composition Study

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/Significance: 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

Development and validation of risk index for cognitive decline using blood-derived markers

ObjectiveWe sought to develop and validate a risk index for prospective cognitive decline in older adults based on blood-derived markers.MethodsThe index was based on 8 markers that have been previously associated with cognitive aging: APOE genotype, plasma β-amyloid 42/40 ratio, telomere length, cystatin C, glucose, C-reactive protein, interleukin-6, and albumin. The outcome was person-specific cognitive slopes (Modified Mini-Mental State Examination) from 11 years of follow-up. A total of 1,445 older adults comprised the development sample. An index based on dichotomized markers was divided into low-, medium-, and high-risk categories; the risk categories were validated with the remaining sample (n = 739) using linear regression. Amyloid was measured on a subsample (n = 865) and was included only in a secondary index.ResultsThe risk categories showed significant differences from each other and were predictive of prospective cognitive decline in the validation sample, even after adjustment for age and baseline cognitive score: the low-risk group (24.8%) declined 0.32 points/y (95% confidence interval [CI]: -0.46, -0.19), the medium-risk group (58.7%) declined 0.55 points/y (95% CI: -0.65, 0.45), and the high-risk group (16.6%) declined 0.69 points/y (95% CI: -0.85, -0.54). Using the secondary index, which included β-amyloid 42/40 (validation n = 279), the low-risk group (26.9%) declined 0.20 points/y (95% CI: -0.42, 0.01), the medium-risk group (61.3%) declined 0.55 points/y (95% CI: -0.72, -0.38), and the high-risk group (11.8%) declined 0.83 points/y (95% CI: -1.14, -0.51).ConclusionsA risk index based on 8 blood-based markers was modestly able to predict cognitive decline over an 11-year follow-up. Further validation in other cohorts is necessary

Associations of BMI and adipose tissue area and density with incident mobility limitation and poor performance in older adults.

BACKGROUND: Obesity is a risk factor for disability, but risk of specific adipose depots is not completely understood. OBJECTIVE: We investigated associations between mobility limitation, performance, and the following adipose measures: body mass index (BMI) and areas and densities of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) in older adults. DESIGN: This was a prospective population-based study of men (n = 1459) and women (n = 1552) initially aged 70-79 y and free from mobility limitation. BMI was determined from measured height and weight. Adipose tissue area and density in Hounsfield units were measured in the thigh and abdomen by using computed tomography. Mobility limitation was defined as 2 consecutive reports of difficulty walking one-quarter mile or climbing 10 steps during semiannual assessments over 13 y. Poor performance was defined as a gait speed <1 m/s after 9 y of follow-up (n = 1542). RESULTS: In models adjusted for disability risk factors, BMI, and areas of VAT, abdominal SAT, and IMAT were positively associated with mobility limitation in men and women. In women, thigh SAT area was positively associated with mobility limitation risk, whereas VAT density was inversely associated. Associations were similar for poor performance. BMI and thigh IMAT area (independent of BMI) were particularly strong indicators of incident mobility limitation and poor performance. For example, in women, the HR (95% CI) and OR (95% CI) associated with an SD increment in BMI for mobility limitation and poor performance were 1.31 (1.21, 1.42) and 1.41 (1.13, 1.76), respectively. In men, the HR (95% CI) and OR (95% CI) associated with an SD increment in thigh IMAT for mobility limitation and poor performance were 1.37 (1.27, 1.47) and 1.54 (1.18, 2.02), respectively. CONCLUSIONS: Even into old age, higher BMI is associated with mobility limitation and poor performance. The amount of adipose tissue in abdominal and thigh depots may also convey risk beyond BMI

Socioeconomic differences in cognitive decline and the role of biomedical factors

PURPOSE: This study examines the association between socioeconomic status and cognitive decline in a community-based cohort of well-functioning older adults and seeks to determine whether this link could be explained by biomedical factors. METHODS: Data are from 2574 men and women aged 70 to 79 years from Pittsburgh, PA, and Memphis, TN, participating in the Health, Aging and Body Composition study (Health ABC). Three indicators of socioeconomic status were used: education, income, and ownership of financial assets. Cognitive decline over 4 years was defined as a decrease of five points or more in the Modified Mini-Mental State Examination (3MS) score. Biomedical factors measured at baseline, included heart disease, cerebrovascular disease, diabetes, hypertension, poor pulmonary function, and high serum levels of inflammatory markers. RESULTS: Adjusted odds ratios were significantly higher in those with low education, low income, and few assets. Odds ratios ranged from 1.51 to 2.16 in the lowest socioeconomic groups. Additional adjustment for biomedical factors reduced the odds ratios of cognitive decline by an average of 2% for education, 5% for income, and 8% for the number of assets. CONCLUSIONS: Low socioeconomic status predicts a decline in cognitive function in older adults and this relationship is not mediated by biomedical factor

Unhealthy lifestyles do not mediate the relationship between socioeconomic status and incident depressive symptoms: the Health ABC study

Background: The relationship between low socioeconomic status (SES) and depressive symptoms is well described, also in older persons. Although studies have found associations between low SES and unhealthy lifestyle factors, and between unhealthy lifestyle factors and depressive symptoms, not much is known about unhealthy lifestyles as a potential explanation of socioeconomic differences in depressive symptoms in older persons. Methods: To study the independent pathways between SES (education, income, perceived income, and financial assets), lifestyle factors (smoking, alcohol use, body mass index, and physical activity), and incident depressive symptoms (Center for Epidemiologic Studies-Depression [CES-D 10] and reported use of antidepressant medication), we used 9 years of follow-up data (1997-2007) from 2,694 American black and white participants aged 70-79 years from the Health, Aging, and Body Composition (Health ABC) study. At baseline, 12.1% of the study population showed prevalent depressive symptoms, use of antidepressant medication, or treatment of depression in the 5 years prior to baseline. These persons were excluded from the analyses. Results: Over a period of 9 years time, 860 participants (31.9%) developed depressive symptoms. Adjusted hazard ratios for incident depressive symptoms were higher in participants from lower SES groups compared with the highest SES group. The strongest relationships were found for black men. Although unhealthy lifestyle factors were consistently associated with low SES, they were weakly related to incident depressive symptoms. Lifestyle factors did not significantly reduce hazard ratios for depressive symptoms by SES. Conclusion: In generally healthy persons aged 70-79 years, lifestyle factors do not explain the relationship between SES and depressive symptoms. © 2013 American Association for Geriatric Psychiatry

Late-Life Depressed Mood and Weight Change Contribute to the Risk of Each Other

OBJECTIVES: Weight change may be considered an effect of depression. In turn, depression may follow weight change. Deteriorations in health may mediate these associations. The objective was to examine reciprocal associations between depressed mood and weight change, and the potentially mediating role of deteriorations in health (interim hospitalizations and incident mobility imitation) in these associations. DESIGN: Prospective observational cohort study SETTINGS: Memphis, Tennessee and Pittsburgh, Pennsylvania PARTICIPANTS: 2406 black and white men and women, aged 70–79 participating in the Health, Aging and Body composition (Health ABC) study. MEASUREMENTS: Depressed mood at baseline (T1) and 3-year follow-up (T4) was measured with the CES-D scale. Three weight change groups (T1–T4) were created: loss (≥5% loss), stable (within ±5% loss or gain), and weight gain (≥5% gain). RESULTS: At T1 and T4, respectively 4.4% and 9.5% of the analysis sample had depressed mood. T1 depressed mood was associated with weight gain over the 3-year period (OR:1.91; 95%CI:1.13–3.22). Weight loss over the 3-year period was associated with T4 depressed mood (OR:1.51; 95%CI:1.05–2.16). Accounting for deteriorations in health in the reciprocal associations between weight change and depressed mood reduced effect sizes between 16–27%. CONCLUSIONS: In this study, depressed mood predicted weight gain over three years, while weight loss over three years predicted depressed mood. These associations were partly mediated through deteriorations in health. Implications for clinical practice and prevention include increased awareness that depressed mood can cause weight change, but can also be preceded by deteriorations in health and weight change

Unhealthy Lifestyles Do Not Mediate the Relationship Between Socioeconomic Status and Incident Depressive Symptoms: The Health ABC study

BACKGROUND: The relationship between low socioeconomic status (SES) and depressive symptoms is well described, also in older persons. Although studies have found associations between low SES and unhealthy lifestyle factors and between unhealthy lifestyle factors and depressive symptoms, not much is known about unhealthy lifestyles as a potential explanation of socioeconomic differences in depressive symptoms in older persons. METHODS: To study the independent pathways between SES (education, income, perceived income, and financial assets), lifestyle factors (smoking, alcohol use, body mass index, and physical activity), and incident depressive symptoms (CES-D 10 and reported use of antidepressant medication), we used 9 years of follow-up data (1997–2007) from 2,694 American black and white participants aged 70–79 from the Health, Aging, and Body Composition (Health ABC) study. At baseline, 12.1% of the study population showed prevalent depressive symptoms, use of antidepressant medication, or treatment of depression in the five years prior to baseline. These persons were excluded from the analyses. RESULTS: Over a period of 9 years time, 860 participants (31.9%) developed depressive symptoms. Adjusted hazard ratios for incident depressive symptoms were higher in participants from lower SES groups compared to the highest SES group. The strongest relationships were found for black men. Although unhealthy lifestyle factors were consistently associated with low SES, they were weakly related to incident depressive symptoms. Lifestyle factors did not significantly reduce hazard ratios for depressive symptoms by SES. CONCLUSION: In generally healthy persons aged 70–79 years lifestyle factors do not explain the relationship between SES and depressive symptoms. (250

Depressive Trajectories and Risk of Disability and Mortality in Older Adults: Longitudinal Findings From the Health, Aging, and Body Composition Study.

BACKGROUND: Depression and disability are closely linked. Less is known regarding clinical and subclinical depressive symptoms over time and risk of disability and mortality. METHODS: Responses 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. RESULTS: Three 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. CONCLUSIONS: Trajectories 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

Personality and Reduced Incidence of Walking Limitation in Late Life: Findings From the Health, Aging, and Body Composition Study

OBJECTIVES. To examine the association between openness to experience and conscientiousness and incident reported walking limitation. METHOD. The study population consisted of 786 men and women aged 71–81 years (M = 75 years, SD = 2.7) participating in the Health, Aging, and Body Composition—Cognitive Vitality Substudy. RESULTS. Nearly 20% of participants (155/786) developed walking limitation during 6 years of follow-up. High openness was associated with a reduced risk of walking limitation (hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.69–0.98), independent of sociodemographic factors, health conditions, and conscientiousness. This association was not mediated by lifestyle factors and was not substantially modified by other risk factors for functional disability. Conscientiousness was not associated with risk of walking limitation (HR = 0.91, 95% CI = 0.77–1.07). DISCUSSION. Findings suggest that personality dimensions, specifically higher openness to experience, may contribute to functional resilience in late life