Introduction

Multifactorial biological processes underpin dysregulation over several individual physiological systems. However, it is challenging to characterize and model this multisystemic dysregulation and its relationship with individual physiologic systems. We operationalized a theory-driven measure of multisystem dysregulation and empirically tested for measurement differences by key characteristics.

Methods

We used the Women's Health and Aging Studies (WHAS) I and II (N = 649), and the Health ABC study (N = 1515). Twelve biomarkers representing multiple systems including stress response (e.g., inflammation), endocrine system, and energy regulation were identified. A series of confirmatory factor analyses (CFA) were conducted to evaluate the interplay between physiological systems and underlying multisystem dysregulation. We evaluated convergent criterion validity of a score for multisystem dysregulation against the physical frailty phenotype, and predictive criterion validity with incidence of walking difficulty and mortality.

Results

A bifactor CFA, a model in which dysregulation of individual systems proceeds independently of generalized dysregulation, fit data well in WHAS (RMSEA: 0.019; CFI: 0.977; TLI: 0.961) and Health ABC (RMSEA: 0.047; CFI: 0.874; TLI: 0.787). The general dysregulation factor was associated with frailty (OR: 2.2, 95 % CI: 1.4, 3.5), and elevated risk of incident walking difficulty and mortality. Findings were replicated in Health ABC.

Discussion

Biomarker data from two epidemiologic studies support the construct of multisystem physiological dysregulation. Results further suggest system-specific and system-wide processes have unique and non-overlapping contributions to dysregulation in biological markers.

Although educational attainment has been consistently related to cognition in adulthood, the mechanisms are still unclear. Early education, and other social learning experiences, may provide the skills, knowledge, and interest to pursue intellectual challenges across the life course. Therefore, cognition in adulthood might reflect continued engagement with cognitively complex environments. Using baseline data from the Baltimore Experience Corps Trial, multiple mediation models were applied to examine the combined and unique contributions of intellectual, social, physical, creative, and passive lifestyle activities on the relationship between education and cognition. Separate models were tested for each cognitive outcome (i.e., reading ability, processing speed, memory). With the exception of memory tasks, findings suggest that education-cognition relations are partially explained by frequent participation in intellectual activities. The association between education and cognition was not completely eliminated, however, suggesting that other factors may drive these associations.

OBJECTIVES: The aim of this study was to determine whether use of diuretics, angiotensin-1 receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), or β-blockers (BB) was associated with a reduced risk of Alzheimer disease (AD) dementia in participants with normal cognition or mild cognitive impairment (MCI). METHODS: Secondary longitudinal data analysis of the Ginkgo Evaluation of Memory Study in older adults at least 75 years of age with normal cognition (n = 1,928) or MCI (n = 320) over a median 6.1-year period using Cox proportional hazard models after adjusting for confounders. RESULTS: Diuretic use was reported by 15.6%, ARB 6.1%, ACE-I 15.1%, CCB 14.8%, and BB 20.5%. Of the 2,248 participants, 290 (13%) developed AD dementia. Hazard ratio for incident AD dementia among participants with normal cognition was 0.51 in diuretic (95% confidence interval [CI] 0.31-0.82), 0.31 in ARB (95% CI 0.14-0.68), 0.50 in ACE-I (95% CI 0.29-0.83), 0.62 in CCB (95% CI 0.35-1.09), and 0.58 in BB (95% CI 0.36-0.93) users and was not significantly altered when mean systolic blood pressure was above 140 mm Hg. In participants with MCI, only diuretic use was associated with decreased risk (hazard ratio = 0.38, 95% CI 0.20-0.73). CONCLUSIONS: Diuretic, ARB, and ACE-I use was, in addition to and/or independently of mean systolic blood pressure, associated with reduced risk of AD dementia in participants with normal cognition, while only diuretic use was associated with reduced risk in participants with MCI.

Background

Hearing impairment (HI) is highly prevalent in older adults and is associated with social isolation, depression, and risk of dementia. Whether HI is associated with broader downstream outcomes is unclear. We undertook this study to determine whether audiometric HI is associated with mortality in older adults.

Methods

Prospective observational data from 1,958 adults ≥70 years of age from the Health, Aging, and Body Composition Study were analyzed using Cox proportional hazards regression. Participants were followed for 8 years after audiometric examination. Mortality was adjudicated by obtaining death certificates. Hearing was defined as the pure-tone average of hearing thresholds in decibels re: hearing level (dB HL) at frequencies from 0.5 to 4kHz. HI was defined as pure-tone average >25 dB HL in the better ear.

Results

Of the 1,146 participants with HI, 492 (42.9%) died compared with 255 (31.4%) of the 812 with normal hearing (odds ratio = 1.64, 95% CI: 1.36-1.98). After adjustment for demographics and cardiovascular risk factors, HI was associated with a 20% increased mortality risk compared with normal hearing (hazard ratio = 1.20, 95% CI: 1.03-1.41). Confirmatory analyses treating HI as a continuous predictor yielded similar results, demonstrating a nonlinear increase in mortality risk with increasing HI (hazard ratio = 1.14, 95% CI: 1.00-1.29 per 10 dB of threshold elevation up to 35 dB HL).

Conclusions

HI in older adults is associated with increased mortality, independent of demographics and cardiovascular risk factors. Further research is necessary to understand the basis of this association and whether these pathways might be amenable to hearing rehabilitation.

Anemia is common in older adults and associated with adverse health outcomes in epidemiological studies. A thorough understanding of the complex pathophysiological mechanisms driving anemia in the elderly is lacking; but inflammation, iron restriction, and impaired erythroid maturation are thought to influence the phenotype. We hypothesized that interleukin-6 contributes to this anemia, given its pro-inflammatory activities, its ability to induce hepcidin antimicrobial peptide, and its negative impact on several tissues in older adults. We tested this hypothesis by comparing changes in indices of inflammation, iron metabolism and erythropoiesis in aged C57BL/6 mice to aged mice with targeted deletions of interleukin-6 or hepcidin antimicrobial peptide. Circulating neutrophil and monocyte numbers and inflammatory cytokines increased with age. Decline in hemoglobin concentration and red blood cell number indicated that C57BL/6, interleukin-6 knockout mice, and hepcidin antimicrobial peptide knockout mice all demonstrated impaired erythropoiesis by 24 months. However, the interleukin-6 knock out genotype and the hepcidin antimicrobial peptide knock out genotype resulted in improved erythropoiesis in aged mice. Increased erythropoietic activity in the spleen suggested that the erythroid compartment was stressed in aged C57BL/6 mice compared to aged interleukin-6 knockout mice. Our data suggest C57BL/6 mice are an appropriate mammalian model for the study of anemia with age. Furthermore, although interleukin-6 and hepcidin antimicrobial peptide are not required, they can participate in the development of anemia in aging mice, and could be targeted, pre-clinically, with existing interventions to determine the feasibility of such agents for the treatment of anemia in older adults.

Experience Corps® (EC) was designed to simultaneously increase cognitive, social, and physical activity through high-intensity volunteerism in elementary school classrooms. It is, therefore, highly likely that EC participation may alter pre-existing patterns of lifestyle activity. This study examined the impact of "real-world" volunteer engagement on the frequency of participation in various lifestyle activities over a 2-year period. Specifically, we examined intervention-related changes on reported activity levels at 12 and 24 months post-baseline using Intention-to-Treat (ITT) and Complier Average Causal Effect (CACE) analyses, which account for the amount of program exposure. ITT analyses indicated that, compared to the control group, EC participants reported modest increases (approximately half a day/month) in overall activity level, especially in intellectual and physical activities 12 months post-baseline. Increases in activity were not found at the 24-month assessment. CACE models revealed similar findings for overall activity as well as for intellectual and physical activities at 12 months. Additionally, CACE findings suggested modest increases in social activity at 12 months and in intellectual and passive activities at 24 months post-baseline. This community-based, health promotion intervention has the potential to impact lifestyle activity, which may lead to long-term increases in activity and to other positive cognitive, physical, and psychosocial health outcomes.

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.

Background

Identifying 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.

Methods

Prospective 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.

Results

In 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.

Conclusions

Hearing 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.

Objectives

The aim of this study was to determine whether use of diuretics, angiotensin-1 receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), or β-blockers (BB) was associated with a reduced risk of Alzheimer disease (AD) dementia in participants with normal cognition or mild cognitive impairment (MCI).

Methods

Secondary longitudinal data analysis of the Ginkgo Evaluation of Memory Study in older adults at least 75 years of age with normal cognition (n = 1,928) or MCI (n = 320) over a median 6.1-year period using Cox proportional hazard models after adjusting for confounders.

Results

Diuretic use was reported by 15.6%, ARB 6.1%, ACE-I 15.1%, CCB 14.8%, and BB 20.5%. Of the 2,248 participants, 290 (13%) developed AD dementia. Hazard ratio for incident AD dementia among participants with normal cognition was 0.51 in diuretic (95% confidence interval [CI] 0.31-0.82), 0.31 in ARB (95% CI 0.14-0.68), 0.50 in ACE-I (95% CI 0.29-0.83), 0.62 in CCB (95% CI 0.35-1.09), and 0.58 in BB (95% CI 0.36-0.93) users and was not significantly altered when mean systolic blood pressure was above 140 mm Hg. In participants with MCI, only diuretic use was associated with decreased risk (hazard ratio = 0.38, 95% CI 0.20-0.73).

Conclusions

Diuretic, ARB, and ACE-I use was, in addition to and/or independently of mean systolic blood pressure, associated with reduced risk of AD dementia in participants with normal cognition, while only diuretic use was associated with reduced risk in participants with MCI.

Recommended levels of physical activity may represent challenging targets for many older adults at risk for disability, leading to the importance of evaluating whether low-intensity activity is associated with health benefits. We examined the cross-sectional association between low-intensity walking activity (<100 steps/min) and health and physical function in a group of older adults. Participants (N = 187; age = 66.8; 91.4% African American; 76.5% female) wore a StepWatch Activity Monitor to measure components of low-intensity walking activity. Only 7% of participants met physical activity guidelines and moderate-intensity activity (≥100 steps/min) contributed only 10% of the total steps/day and 2% of the total min/day. Greater amount, frequency, and duration of low-intensity activity were associated with better self-report and performance-based measures of physical function, better quality of life, and fewer depressive symptoms (ps < .05). The cross-sectional relationship between low-intensity activity and health outcomes important to independent function suggests that we further explore the longitudinal benefits of low-intensity activity.