BACKGROUND: Social support and social networks have long been postulated to impact health outcomes but their impact on life expectancy and disability in older adults remains poorly quantified. METHODS: As part of the Cardiovascular Health Study, we followed 5,749 adults aged 65 years and older from 4 US field centers for 25 years. We assessed the Lubben social network score [range 0-50] and a social support score [range 0-24] derived from the Interpersonal Support Evaluation List (ISEL-12) in two consecutive years starting at study recruitment. We used remaining years of life (YOL) from study enrollment to death to approximate life expectancy. We defined years of active life (YAL) as the number of study years in which participants lived without any difficulties in activities of daily living. We used compression of disability to reflect the proportion of life lived able (YAL/YOL). We used linear regression to adjust for socio-demographics and comorbidity. RESULTS: The mean (standard deviation [SD]) scores were 32.3 ± 6.8 points for social network score and 8.3 ± 2.4 points for social support score. For every 1-SD increase in social network score, adjusted participant life expectancy was 0.40 years higher (95% CI 0.22-0.58; p<0.0001) and disability-free life expectancy 0.35 years higher (95% CI 0.18-0.53; p<0.0001). The association with life expectancy was modified by participant age (p<0.001), but it remained significant even among participants aged ≥75 years (3 months per SD; 95% CI 0.1-6 months, p = 0.04). Further adjustment for frailty did not attenuate the estimates. The social support scale was not significantly associated with YOL or YAL after adjustment for social network score, and neither measure was associated with compression of disability. DISCUSSION: In older adults, higher social network scores are significantly associated with longer life expectancy and disability-free life expectancy.

BACKGROUND: Myostatin, a cytokine produced by skeletal muscle, may influence Alzheimers disease (AD) pathogenesis, but sparse evidence exists in humans. We assessed the association between circulating levels of myostatin at Year 1 and plasma levels of β-amyloid 42/40 at Year 2, a marker of AD pathology, in a biracial cohort of older adults. METHODS: We studied 403 community-dwelling older adults enrolled in the Health, Aging and Body Composition Study from Memphis, Tennessee, and Pittsburgh, PA. Mean age was 73.8 ± 3 years; 54% were female; and 52% were Black. Serum myostatin levels were measured at Year 1, plasma β-amyloid 42/40 levels in Year 2 (higher ratio indicating lower amyloid load). Multivariable linear regression analyses tested the association of serum myostatin with plasma levels of β-amyloid 42/40 adjusted for computed-tomography-derived thigh muscle cross-sectional area, demographics, APOe4 allele, and risk factors for dementia. We tested for 2-way.interactions between myostatin and race or sex; results were stratified by race and sex. RESULTS: In multivariable models, myostatin was positively associated with plasma levels of β-amyloid 42/40 (standardized regression coefficient: 0.145, p = .004). Results were significant for white men and women (0.279, p = .009, and 0.221, p = .035, respectively) but not for Black men or women; interactions by race and gender were not statistically significant. CONCLUSIONS: Higher serum myostatin was associated with lower amyloid burden, independently of APOe4 alleles, muscle area and other established risk factors for dementia. The role of myostatin in AD pathogenesis and the influence of race should be further investigated.

Background

Musculoskeletal pain is highly prevalent and limits mobility in older adults. A potential mechanism by which pain affects mobility could be through its negative impact on the brain. We examined whether structural integrity of cerebral gray and white matter (WM) mediated the relationship between pain and mobility in community-dwelling older adults.

Methods

Musculoskeletal pain, gait speed, and neuroimaging data were obtained concurrently from the Health ABC study (mean age = 83/56% female, n = 212). Microstructural gray matter integrity was measured by mean diffusivity (MD), WM microstructure and macrostructure were measured by fractional anisotropy (FA) and WM hyperintensities (WMH), respectively. Regression models were adjusted for gray matter atrophy, age, gender, medication use, and obesity. Bootstrapped mediation methods were used (1,000 bootstrapped samples, 95% confidence intervals).

Results

The associations of musculoskeletal pain with WMH (β = .19, p < .05) and FA (β = -.18, p < .05) were robust to adjustment for gender, medication use, age, body mass index (BMI), and brain atrophy. Participants who experienced both knee and back pain had a significantly slower gait speed (~0.11 m/s) than those without knee or back pain (p < .05) independent of gender, medication, age, and BMI. WMH and FA significantly mediated the pain-gait speed relationship. Associations between pain and MD were not significant, and MD did not modify the association between pain and gait speed.

Conclusions

Cerebral WM integrity may contribute to the detrimental effects of musculoskeletal pain on mobility, although pre-existing WM integrity may also simultaneously amplify pain and decrease mobility. Future studies are needed to further understand whether successful pain management may significantly improve both brain health and mobility.

Background

Slowing 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.

Hypothesis

Information processing is cross-sectionally associated with WM micro-structure independent of overt macro-structural abnormalities and also independent of health related characteristics.

Methods

Imaging 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.

Results

The 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.

Interpretation

DTI 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.

Poor physical function is highly prevalent with aging, and strongly associated with D3-creatine muscle mass/weight. Using metabolomics, we previously identified several triglycerides consisting mostly of polyunsaturated fatty acids that were higher in older adults with good mobility. Here, we sought to further investigate polyunsaturated fatty-acid-related metabolites, i.e., oxylipins, and their associations with D3-creatine muscle mass/weight, gait speed, grip strength, and the Short Physical Performance Battery among 463 older men from the Osteoporotic Fractures in Men Study (MrOS). Oxylipins were measured in fasting serum using liquid chromatography-mass spectrometry. Muscle mass was estimated using D3-creatine dilution and adjusted for body size. We used linear regression to determine oxylipins associated with D3-creatine muscle mass/weight and physical performance, while adjusting for age, education, physical activity, Western dietary pattern, fish oil supplementation, and multiple comparisons. Among 42 oxylipins, none were associated with grip strength and 3 were associated with the Short Physical Performance Battery. In contrast, 18 and 17 oxylipins were associated with D3-creatine muscle mass/weight and gait speed, respectively. A subset of associations between oxylipins and gait speed were partially attenuated by D3-creatine muscle mass/weight. Higher levels of fatty acid alcohol and ketone oxylipins tended to be most strongly associated with gait speed and D3-creatine muscle mass/weight, potentially reflecting anti-inflammatory activity from these select oxylipins in MrOS older men.

Objective

To examine whether observed differences in dementia rates between black and white older people living in the community could be explained by measures of socioeconomic status (income, financial adequacy, education, and literacy) and health related factors.

Design

Prospective cohort study.

Setting

General community from two clinic sites in the United States (Pittsburgh, Pennsylvania and Memphis, Tennessee).

Participants

2457 older people (mean age 73.6 years; 1019 (41.5%) black; 1233 (50.2%) women), dementia-free at baseline, in the Health, Aging, and Body Composition study.

Main outcome measure

Dementia was determined over 12 years (ending January 2011) by prescribed dementia drugs, hospital records, and decline in global cognitive scores. The influence of socioeconomic status and health related factors on dementia rates was examined in a series of Cox proportional hazard models in which these variables were added sequentially in covariate blocks.

Results

Over follow-up, 449 (18.3%) participants developed dementia. Black participants were more likely than white participants to develop dementia (211 (20.7%) v 238 (16.6%), P<0.001; unadjusted hazard ratio 1.44, 95% confidence interval 1.20 to 1.74). The hazard ratio lessened somewhat after adjustment for demographics, apolipoprotein E e4, comorbidities, and lifestyle factors (1.37, 1.12 to 1.67) but was greatly reduced and no longer statistically significant when socioeconomic status was added (1.09, 0.87 to 1.37).

Conclusion

These findings suggest that differences in the burden of risk factors, especially socioeconomic status, may contribute to the higher rates of dementia seen among black compared with white older people. Strategies aimed at reducing these disparities may favorably affect the incidence of dementia.

Background

The cerebellum plays an important role in mobility and cognition. However, it is unclear which regions of the cerebellum are associated with gait speed and information-processing ability in older adults without overt brain damage.

Methods

Cross-sectional associations between cerebellar gray matter volumes (GMV), gait speed, and information-processing ability were explored in 231 community-dwelling adults (mean age: 83 years, 48% black, 58% female). We measured gait speed on an automated walkway and information-processing ability on the Digit Symbol Substitution test (DSST). Total and regional cerebellar GMV was measured on 3T-magnetic resonance imaging. Lobar GMV of the cerebellum, obtained by an automated parcellation process, were aggregated based on the cognitive (lobules VI, VII, VIII and crus I, II), sensorimotor (lobules II, IV, V), and vestibular (lobules IX and X) functions ascribed to the cerebellar regions.

Results

Larger cerebellar GMV correlated with faster gait speed and superior DSST scores (both p < .001) independent of age, gender, atrophy, and small vessel disease. After adjusting for age, gender, and atrophy, larger cognitive cerebellar GMV correlated with both faster gait speed (p = .04) and higher DSST scores (p < .001), larger sensorimotor cerebellar GMV correlated significantly with DSST alone (p = .02), and the vestibular cerebellar GMV with neither. The association between cognitive cerebellar GMV and gait speed was no longer significant after adjusting for DSST score in the linear regression models.

Conclusions

The relationship between gait speed and cerebellar GMV is influenced by information-processing ability, and this relationship is stronger in subregions ascribed to cognitive than vestibular or sensorimotor functions.

Importance

Cerebral white matter hyperintensities (WMHs) are involved in the evolution of impaired mobility and executive functions. Executive functions and mobility are also associated. Thus, WMHs may impair mobility directly, by disrupting mobility-related circuits, or indirectly, by disrupting circuits responsible for executive functions. Understanding the mechanisms underlying impaired mobility in late life will increase our capacity to develop effective interventions.

Objective

To identify regional WMHs most related to slower gait and to examine whether these regional WMHs directly impact mobility, or indirectly by executive functions.

Design

Cross-sectional study. Twenty-one WMH variables (i.e., total WMH volume and WMHs in 20 tracts), gait speed, global cognition (Modified Mini-Mental State Examination; 3MS), and executive functions and processing speed (Digit-Symbol Substitution Test; DSST) were assessed. An L1-L2 regularized regression (i.e., Elastic Net model) identified the WMH variables most related to slower gait. Multivariable linear regression models quantified the association between these WMH variables and gait speed. Formal tests of mediation were also conducted.

Setting

Community-based sample.

Participants

Two hundred fifty-three adults (mean age: 83years, 58% women, 41% black).

Main outcome measure

Gait speed.

Results

In older adults with an average gait speed of 0.91m/sec, total WMH volume, WMHs located in the right anterior thalamic radiation (ATRR) and frontal corpuscallosum (CCF) were most associated with slower gait. There was a >10% slower gait for each standard deviation of WMH in CCF, ATRR or total brain (standardized beta in m/sec [p value]: -0.11 [p=0.046], -0.15 [p=0.007] and -0.14 [p=0.010], respectively). These associations were substantially and significantly attenuated after adjustment for DSST. This effect was stronger for WMH in CCF than for ATRR or total WMH (standardized beta in m/sec [p value]: -0.07 [p=0.190], -0.12 [p=0.024] and -0.10 [p=0.049], respectively). Adjustment for 3MS did not change these associations. The mediation analyses also found that DSST significantly mediated the associations between WMHs and gait speed. Our models were adjusted for age, sex, BMI, quadriceps strength, years of education, standing height, and prevalent hypertension.

Conclusion

The impact, direct or indirect, of WMHs on gait speed depended on their location and was mediated by executive function. Thus, multi-faceted interventions targeting executive control functions as well as motor functions, such as balance and strength training, are candidates to the maintenance of mobility across the lifespan.

CONTEXT: αKlotho is a hormone and co-receptor for fibroblast growth factor 23 (FGF23), a hormone that downregulates active vitamin D synthesis and promotes phosphate excretion. Low αKlotho and high FGF23 occur in chronic kidney disease (CKD). OBJECTIVE: We aimed to assess the relationships of αKlotho and FGF23 with mobility disability in community-dwelling older adults. DESIGN AND SETTING: We estimated associations of plasma-soluble αKlotho and serum FGF23 concentrations with mobility disability over 6 years. Additional analyses was stratified by CKD. PARTICIPANTS: Participants included 2751 adults (25.0% with CKD), aged 71 to 80 years, from the 1998 to 1999 Health, Aging, and Body Composition Study visit. MAIN OUTCOME MEASURES: Walking disability and stair climb disability were defined as self-reported a lot of difficulty or an inability to walk a quarter mile and climb 10 stairs, respectively. RESULTS: Median (interquartile range [IQR]) serum FGF23 and plasma soluble αKlotho concentrations were 46.6 (36.7, 60.2) pg/mL and 630.4 (478.4, 816.0) pg/mL, respectively. After adjustment, higher αKlotho concentrations were associated with lower walking disability rates (Rate Ratio [RR] highest vs. lowest tertile = 0.74; 95% confidence interval l [CI] = 0.62, 0.89; P = 0.003). Higher FGF23 concentrations were associated with higher walking disability rates (RR highest vs. lowest tertile = 1.24; 95%CI = 1.03, 1.50; P = 0.005). Overall, higher αKlotho combined with lower FGF23 was associated with the lowest walking disability rates (P for interaction = 0.023). Stair climb disability findings were inconsistent. No interactions with CKD were statistically significant (P for interaction > 0.10). CONCLUSIONS: Higher plasma soluble αKlotho and lower serum FGF23 concentrations were associated with lower walking disability rates in community-dwelling older adults, particularly those without CKD.

BACKGROUND: Based on studies from animal models, growth differentiation factor-11 (GDF-11) may have rejuvenating effects in humans. GDF-11 has high sequence homology with GDF-8 (also known as myostatin); follistatin and follistatin-like protein-3 (FSTL-3) are inhibitory proteins of both GDF-8 and GDF-11. METHODS: Using highly specific liquid chromatography with tandem mass spectrometry assays for GDF-11 and GDF-8 and immunoassays for follistatin and FSTL-3, we quantified the association of these factors with muscle size, strength, and physical performance in 2 prospective cohort studies of community-dwelling older adults (Health, Aging, and Body Composition study [Health ABC] and Cardiovascular Health Study [CHS]). RESULTS: GDF-8 levels were positively associated with thigh muscle cross-sectional area and density in Health ABC (data not available in CHS). GDF-8 levels were positively associated with lean mass (a surrogate of muscle mass) in Health ABC but not CHS, and grip strength in CHS but not Health ABC. FSTL-3 (and perhaps follistatin) was negatively associated with lean mass and had variable associations with other variables. In contrast, GDF-11 was not significantly associated with strength or performance. CONCLUSIONS: GDF-8 and its binding proteins, follistatin and FSTL-3, may constitute a counterregulatory system (chalones) to restrain age-related loss of muscle mass and strength.