Background The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.
Methods We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual–participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.
Results For people born between 1900 and 1960, mean adult height increased 0.5–1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96–0.99) for death from any cause, 0.94 (0.93–0.96) for death from vascular causes, 1.04 (1.03–1.06) for death from cancer and 0.92 (0.90–0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12–1.42) for risk of melanoma death to 0.84 (0.80–0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.
Conclusion Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
Height; cardiovascular disease; cancer; cause-specific mortality; epidemiological study; meta-analysis
To determine the effects of chronic pain on the development of disability and decline in physical performance over time among older adults.
Longitudinal cohort study with 18 months follow-up.
634 community-dwelling older adults aged >64 years.
Chronic pain assessment consisted of musculoskeletal pain locations, and pain severity and pain interference by subscales of the Brief Pain Inventory. Disability was self-reported as any difficulty in mobility and basic and instrumental activities of daily living (ADL, IADL). Mobility performance was measured using the Short Physical Performance Battery (SPPB). Relationships between baseline pain and incident disability in 18 months were determined using risk ratios (RRs) from multivariable Poisson regression models.
Almost 65% of participants reported chronic musculoskeletal pain at baseline. New onset of mobility difficulty at 18-months was strongly associated with baseline pain distribution: 7% (no sites), 18% (1 site), 24% (multisite) and 39% (widespread pain, p-value for trend <0.001). Similar graded effects were found for other disability measures. Elders with multisite or widespread pain had at least a three-fold increased risk for onset of mobility difficulty compared to their peers without pain after adjusting for disability risk factors (multisite pain: RR=2.95, 95%CI, 1.58–5.50; widespread pain: RR=3.57, 95%CI, 1.71–7.48). Widespread pain contributed to decline in mobility performance (1 point decline in SPPB, RR=1.47, 95%CI, 1.08–2.01). Similar associations were found for baseline pain interference predicting subsequent mobility decline and (I)ADL disability. Weaker and less consistent associations were observed with pain severity.
Older community-dwelling adults living with chronic pain in multiple musculoskeletal locations have a substantial increased risk for developing disability over time and for clinically meaningful decline in mobility performance.
widespread chronic pain; older adults; mobility limitation; activities of daily living
Although metabolic syndrome (MS) is a typical condition of middle-aged/older person, the association between MS and mortality risk has not been confirmed in people over 65 years. We hypothesized that while in the elderly MS phenotype might lose its value in predicting mortality risk, the two core factors of MS, i.e. insulin resistance (IR) and low-grade systemic inflammation (LGSI) would not.
1011 community-dwelling older individuals (InCHIANTI study) were included. MS phenotype was defined by NCEP-ATP-III criteria. IR was calculated by HOMA; high-sensitivity C-reactive protein was measured by ELISA. Subjects were divided into four groups based on presence/absence of IR (HOMA ≥2.27) and LGSI (hs-CRP ≥ 3g/L): Group 1: no IR/LGSI (reference); Group 2: LGSI only; Group 3: IR only; Group 4: IR+LGSI. Hazard Ratios (HR) for 9-years cardiovascular (CVD) and total mortality, according to IR/LGSI groups, were estimated in subjects with (n.311) and without MS by Cox model.
31.8% of subjects with MS phenotype had no IR, 45.3% had no LGSI; moreover, 51% of subjects with both IR and LGSI didn’t display the MS phenotype. MS phenotype was not associated with CVD (HR:1.29; 95%C.I.:0.92–1.81) or total (HR:1.07; 95%C.I.:0.86–1.34) mortality risk, whereas the presence of IR plus LGSI was associated with increased CVD (no MS: HR 2.07, 95%CI:1.12–3.72; MS: HR 9.88, 95%CI:2.18–4), and overall (no MS: HR 1.72, 95%CI:1.001–3.17; MS: HR 1.51, 95%CI:1.02–2.28) mortality risk. The presence of IR (HR: 6.90, 95%CI:1.45–32) or LGSI (HR 7.56, 95%CI:1.63–35) was associated with CVD mortality, only among individuals with MS phenotype.
Among community dwelling older individuals, IR and LGSI, but not MS phenotype, was associated with 9-years overall and CVD mortality risk. Since a reduced “overlap” between MS phenotype and its physiopathological core (IR and LGSI) might be present with aging, we suggest that the definition of MS might be more holistic in advanced age, and probably comprise the measurement of IR and LGSI.
Insulin Resistance; C Reactive Protein; Mortality; Metabolic Syndrome; Elderly
Lower extremity physical performance measured at one point in time is a powerful predictor of future disability. Whether information on previous lower extremity performance adds independent information to disability prediction compared to a single measure alone is unknown.
Data are from community-dwelling men and women aged greater than or equal to 65 years enrolled in the Invecchiare in Chianti study who were free of mobility and activities of daily living (ADL) disability at baseline and at 3-year follow-up (n = 891). Walking speed and Short Physical Performance Battery were examined at baseline and at the 3-year follow-up (zero-time). Logistic regression analysis was used to examine the associations between physical performance measures and incident mobility and ADL disability detected at the 6-year and 9-year follow-up.
Walking speed and Short Physical Performance Battery score assessed at the zero-time strongly predicted development of mobility and ADL disability during the subsequent 6 years independent of walking speed/Short Physical Performance Battery score 3 years prior.
Current lower extremity performance is a strong risk factor for subsequent mobility and ADL disability and is independent of performance 3 years prior, which has negligible independent prognostic value.
Aging; Disability; Measurement; Mobility; Physical performance; Walking speed.
peripheral vascular disease; exercise
To determine the distribution of influenza vaccine coverage in the U.S. in 2008.
Design, Setting, and Participants
Cross-sectional analysis of the 2008 Behavioral Risk Factor Surveillance Survey (BRFSS). The BRFSS employs random-digit dialing to interview non-institutionalized adults in the U.S. and the territories. The sample was restricted to persons ≥50 years (N=249,723).
Participants were asked if they had a flu shot during the past 12 months.
In 2008, 42.0% of adults age 50–64 years and 69.5% of adults ≥65 years reported receiving a flu shot in the past 12 months. Vaccine coverage generally increased with advancing age (p<0.001), higher levels of education (p<0.001) and total household income (p<0.001), and greater morbidity (p<0.001). In 50–64 year olds, vaccine prevalence was lower in men than in women (39.9% vs 44.1%; p<0.001), although no significant differences were observed in older adults. Within each 5-year interval of age, non-Hispanic blacks and Hispanics had significantly lower vaccine prevalence than non-Hispanic whites (p<0.001 for all comparisons). Among participants ≥65 years, non-Hispanic blacks and Hispanics were 56% [adjusted prevalence ratio (PR): 1.56 (95% CI: 1.48, 1.64)] and 44% [adjusted PR: 1.44 (95% CI: 1.35, 1.54)], respectively, more likely to be unvaccinated compared with non-Hispanic whites, adjusting for age and sex. Racial/ethnic disparities in vaccine coverage narrowed with increasing number of diseases; however, these disparities remained significant in older adults with ≥2 diseases (p<0.05).
There were large disparities in influenza vaccine coverage in 2008, particularly across race/ethnicity and socioeconomic position. Accordingly, more targeted interventions are needed to improve vaccine delivery to disadvantaged segments of the U.S. population.
Influenza; influenza vaccines; aged; health disparities; public health
An important challenge in epidemiology is the difficulty in inferring causality from observational studies. Even the best longitudinal studies have limitations in this regard, and when clinical trials are feasible they will provide more definite evidence of causality. However, even when clinical trials are feasible, we can learn a great deal about the disease process, assessment techniques, subject selection criteria, and the impact of potential interventions from longitudinal studies. This review covers the theoretical issues supporting the value and limitations of longitudinal studies, the practical utilization in clinical trials of different aspects of knowledge that can be gained from longitudinal studies, critical issues in the translation of longitudinal observational studies into clinical trials, and the value of observational studies in broadening the applicability of specific trials. Relevant issues are illustrated with examples of both unsuccessful and successful trials, with a major emphasis on clinical trials of physical activity in older persons.
longitudinal studies; observational studies; clinical trials
Muscle impairment is a common condition in older people and a powerful risk factor for disability and mortality. The aim of this study was to apply the European Working Group on Sarcopenia in Older People criteria to estimate the prevalence and investigate the clinical correlates of sarcopenia, in a sample of Italian community-dwelling older people.
Cross-sectional analysis of 730 participants (74% aged 65 years and older) enrolled in the InCHIANTI study. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People criteria using bioimpedance analysis for muscle mass assessment. Logistic regression analysis was used to identify the factors independently associated with sarcopenia.
Sarcopenia defined by the European Working Group on Sarcopenia in Older People criteria increased steeply with age (p < .001), with 31.6% of women and 17.4% of men aged 80 years or older being affected by this condition. Higher education (odds ratio: 0.85; 95% CI: 0.74–0.98), lower insulin-like growth factor I (lowest vs highest tertile, odds ratio: 3.89; 95% CI: 1.03–14.1), and low bioavailable testosterone (odds ratio: 2.67; 95% CI: 1.31–5.44) were independently associated with the likelihood of being sarcopenic. Nutritional intake, physical activity, and level of comorbidity were not associated with sarcopenia.
Sarcopenia identified by the European Working Group on Sarcopenia in Older People criteria is a relatively common condition in Italian octogenarians, and its prevalence increases with aging. Correlates of sarcopenia identified in this study might suggest new approaches for prevention and treatment of sarcopenia.
Sarcopenia; Community-dwelling older people; Frail elderly.
Evidence for a role of leptin in depression is limited and conflicting. Inconclusive findings may be explained by the complex effect of obesity on leptin signaling. In particular, both hyperleptinemia due to leptin resistance in obese persons as well as low leptin in lean persons can imply that low leptin biological signaling is associated with an increased risk of significant depressive symptoms. We tested whether the relationship between leptin and depressive symptoms is modulated by abdominal adiposity in two population-based studies.
Data were from 851 participants (65–94 years) of the InCHIANTI Study and 1,064 (26–93 years) of the Baltimore Longitudinal Study of Aging (BLSA). Plasma concentrations of leptin, waist circumference and depressive symptoms via the Center for Epidemiological Studies-Depression scale (CES-D) were assessed. In longitudinal InCHIANTI analyses onset of depressed mood (CES-D≥20) was evaluated over a 9-year follow-up.
In pooled cross-sectional analyses the interaction between leptin and waist circumference was significantly associated with CES-D scores ((log)leptin-by-waist interaction p=0.01). Also in longitudinal analyses, the (log)leptin-by-waist interaction term significantly (p=0.04) predicted depressed mood onset over time; depressed mood risk was especially increased for high levels of both leptin and waist circumference.
The present findings suggest that low leptin signaling rather than low leptin concentration is a risk factor for depression. Future studies should develop proxy measures of leptin signaling by combining information on abdominal adiposity and leptin level to be used for clinical and research applications.
leptin; depression; abdominal adiposity; obesity; aging
To examine the association of stopping to rest during a 400 meter usual-pace walk test (400-MWT) with incident mobility disability in older persons with functional limitations.
Prospective cohort study
Four hundred twenty-four participants of the Lifestyle Intervention and Independence for Elders Pilot (LIFE-P) Study aged 70–89 years, having functional limitation (summary score =9 on the Short Physical Performance Battery (SPPB)), and being able to complete the 400-MWT within 15 minutes.
Rest stops during the 400-MWT were recorded. The onset of mobility disability, defined as being unable to complete the 400-MWT or taking more than 15 minutes to do so, was recorded at months 6 and 12.
Fifty-four (12.7%) participants rested during the 400-MWT at baseline, of whom 37.7% experienced mobility disability during follow-up versus 8.6% of those not stopping to rest. Performing any rest stop was strongly associated with incident mobility disability at follow-up (odds ratio (OR) = 5.4, 95% confidence interval (CI) = 2.7–10.9) after adjustment for age, gender, and clinic site. This association was diminished, but remained statistically significant, after further adjusting for SPPB and the time to complete the 400-MWT simultaneously (OR = 2.6, 95%CI = 1.2–5.9).
Stopping to rest during the 400-MWT is strongly associated with incident mobility disability in non-disabled older persons with functional limitations. Given the prognostic value, rest stops should be recorded as part of the standard assessment protocol for the 400-MWT.
mobility disability; aging; physical performance test
To assess whether selenium and carboxymethyl-lysine (CML), two biomarkers of oxidative stress, are independent predictors of anemia in older, community-dwelling adults.
Plasma selenium, CML, folate, vitamin B12, testosterone, and markers of iron status and inflammation were measured at baseline in 1,036 adults, ≥65 years, in the InCHIANTI Study, a population-based cohort study of aging in Tuscany, Italy, and examined in relationship to prevalent anemia and incident anemia over 6 years of follow-up.
At enrollment, 11.6% of participants were anemic. Of 472 participants who were non-anemic at enrollment 72 (15.3%) developed anemia within 6 years of follow-up. At enrollment, plasma CML in the highest quartile (>425 ng/mL) and plasma selenium in the lowest quartile (<66.6 μg/L) predicted incident anemia (Hazards Ratio [H.R.] 1.67, 95% Confidence Interval [C.I.] 1.07–2.59, P = 0.02; H.R. 1.55, 95% C.I.1.01–2.38, P = 0.05, respectively) in a multivariate Cox proportional hazards model that adjusted for age, education, body mass index, cognition, inflammation, red cell distribution width, ferritin, vitamin B12, testosterone, and chronic diseases.
Elevated plasma carboxymethyl-lysine and low plasma selenium are long-term independent predictors of anemia among older community-dwelling adults. These findings support the idea that oxidative stress contributes to the development of anemia.
advanced glycation end products; aging; anemia; carboxymethyl-lysine; oxidative stress; selenium
Accidents (including motor vehicle accidents) are a leading cause of death among American Indians/Alaskan Natives (AI/AN). The purpose of this study was to examine geographic variation and the existence of a seatbelt law on seatbelt use among AI/AN and non-Hispanic Whites (NHW).
Self-reported seatbelt behavior data from the 1997 and 2002 Behavioral Risk Factor Surveillance System (BRFSS) were analyzed in 2006–2007 and were restricted to AI/AN (n=4,310 for 2002, and n=1,758 for 1997) and NHW (n=193,617 for 2002, and n=108,551 for 1997) aged 18 years and older.
Seatbelt non-use varied significantly across geographic regions for both AI/AN and NHW. For example, AI/AN living in the Northern Plains [odds ratio (OR)=12.4 (95% confidence interval (CI): 6.5, 23.7)] and Alaska [OR=10.3 (95%CI: 5.3, 19.9)] had significantly higher seatbelt non-use compared to AI/AN living in the West. In addition, compared to those residing in urban areas, those living in rural areas were 60% more likely in NHW and 2.6 times more likely in AI/AN not to wear a seatbelt. Both AI/AN and NHW living in states without primary seatbelt laws were approximately twice as likely to report seatbelt non-use in 2002 as those living in states with primary laws. In states with primary laws enacted between 1997 and 2002, AI/AN experienced greater decline in seatbelt non-use than NHW.
Seatbelt use among AI/AN and NHW varied significantly by region and urban-rural residency in 2002. Primary seatbelt laws appear to help reduce regional and racial disparities in seatbelt non-use.
In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining if physical activity prevents or delays mobility disability.
To test the hypothesis that a long-term structured physical activity program is more effective than a health education program (also referred to as a successful aging program) in reducing the risk of major mobility disability.
Design, Setting, and Participants
The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial that enrolled participants between February 2010 and December 2011, who participated for an average of 2.6 years. Follow-up ended in December 2013. Outcome assessors were blinded to the intervention assignment. Participants were recruited from urban, suburban and rural communities at 8 field centers throughout the US. We randomized a volunteer sample of 1,635 sedentary men and women aged 70–89 years who had physical limitations, defined as a score on the Short Physical Performance Battery of 9 or below, but were able to walk 400 m.
Participants were randomized to a structured moderate intensity physical activity program (n=818) done in a center and at home that included including aerobic, resistance and flexibility training activities or to a health education program (n=817) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises.
Main Outcomes and Measures
The primary outcome was major mobility disability objectively defined by loss of ability to walk 400 m.
Incident major mobility disability occurred in 30.1% (n=246/818) of physical activity and 35.5% (n=290/817) of health education participants (HR=0.82, 95%CI=0.69–0.98, p=0.03). Persistent mobility disability was experienced by 120/818 (14.7%) physical activity and 162/817 (19.8%) health education participants (HR=0.72; 95%CI=0.57–0.91; p=0.006). Serious adverse events were reported by 404/818 (49.4%) of the physical activity and 373/817 (45.7%) of the health education participants (Risk Ratio=1.08; 95%CI=0.98–1.20).
Conclusions and Relevance
A structured moderate intensity physical activity program, compared with a health education program, reduced major mobility disability over 2.6 years among older adults at risk of disability. These findings suggest mobility benefit from such a program in vulnerable older adults.
ClinicalsTrials.gov identifier NCT01072500.
To determine whether higher levels of inflammatory blood markers, D-dimer, and homocysteine were associated with greater impairment in lower extremity functioning in persons with peripheral arterial disease (PAD).
Three Chicago-area medical centers.
Four hundred twenty-three persons with PAD (ankle-brachial index (ABI) <0.90).
Lower extremity performance was assessed using the 6-minute walk and with usual- and fast-paced 4-m walking speed. Blood markers were D-dimer, C-reactive protein (CRP), interleukin-6 (IL-6), soluble vascular cellular adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), and homocysteine. Calf muscle area was measured using computed tomography.
Adjusting for confounders, higher levels of D-dimer (P<.001), IL-6 (P<.001), sVCAM-1 (P=.006), CRP (P=.01), homocysteine (P=.004), and sICAM-1 (P=.046) were associated with poorer 6-minute walk performance. Higher levels of D-dimer (P<.001), IL-6 (P=.003), sVCAM-1 (P=.001), and homocysteine (P=.005) were associated with slower usual-paced 4-m walking speed. Higher levels of D-dimer, sVCAM-1, sICAM-1, IL-6, and homocysteine were associated with slower fast-paced walking speed. Results were attenuated after additional adjustment for calf muscle area.
Higher levels of inflammation and D-dimer were associated with poorer lower extremity performance in participants with PAD, independent of confounders including ABI.
intermittent claudication; peripheral vascular disease; physical functioning; inflammation
Recruitment of older adults into long-term clinical trials involving behavioral interventions is a significant challenge. The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase 3 multicenter randomized controlled multisite trial, designed to compare the effects of a moderate-intensity physical activity program with a successful aging health education program on the incidence of major mobility disability (the inability to walk 400 m) in sedentary adults aged 70–89 years, who were at high risk for mobility disability (scoring ≤9 on the Short Physical Performance Battery) at baseline.
Recruitment methods, yields, efficiency, and costs are described together with a summary of participant baseline characteristics. Yields were examined across levels of sex, race and ethnicity, and Short Physical Performance Battery, as well as by site.
The 21-month recruiting period resulted in 14,812 telephone screens; 1,635 participants were randomized (67.2% women, 21.0% minorities, 44.7% with Short Physical Performance Battery scores ≤7). Of the telephone-screened participants, 37.6% were excluded primarily because of regular participation in physical activity, health exclusions, or self-reported mobility disability. Direct mailing was the most productive recruitment strategy (59.5% of randomized participants). Recruitment costs were $840 per randomized participant. Yields differed by sex and Short Physical Performance Battery. We accrued 11% more participant follow-up time than expected during the recruitment period as a result of the accelerated recruitment rate.
The LIFE Study achieved all recruitment benchmarks. Bulk mailing is an efficient method for recruiting high-risk community-dwelling older persons (including minorities), from diverse geographic areas for this long-term behavioral trial.
Mobile disability; Older adults; Physical activity; Minority recruitment; Randomized controlled trial.
The measurement of mobility is essential to both aging research and clinical practice. A newly developed self-report measure of mobility, the mobility assessment tool—short form (MAT-sf), uses video animations to improve measurement accuracy/precision. Using a large baseline data set, we recalibrated the items, evaluated the extent to which older patients’ self-efficacy (i.e., confidence) for walking was related to MAT-sf scores beyond their actual 400-m walk time, and assessed the relationship of the MAT-sf with body mass index and other clinical variables.
The analyses employed baseline data from the Lifestyle Interventions and Independence for Elders Study.
Item recalibration demonstrated that the MAT-sf scoring algorithm was robust. In an analysis with 400-m walk time and self-efficacy regressed on the MAT-sf, both variables shared unique variance with the MAT-sf (p < .001). The MAT-sf was inversely related to several comorbidities, most notably hypertension and arthritis (p < .001), and scores were lowest when body mass index ≥ 35kg/m2. Finally, MAT-sf scores were directly related to Short Physical Performance Battery scores, inversely related to difficulty with activities of daily living (p < .001) and higher for men than for women (p < .001).
The findings extend the validity and clinical utility of this innovative tool for assessing self-reported mobility in older adults. Longitudinal data on the MAT-sf from the Lifestyle Interventions and Independence for Elders Study will enable us to evaluate the relative contributions of self-report and performance-based measures of mobility on important health outcomes.
Mobility; Geriatric assessment; Physical function; MAT-sf
The study sought to determine the prevalence and impact of pain in a
nationally representative sample of older adults in the United States (US). Data
from the 2011 National Health and Aging Trends Study were analyzed. In-person
interviews were conducted in 7,601 adults ages ≥65 years. The response
rate was 71.0% and all analyses were weighted to account for the
sampling design. The overall prevalence of bothersome pain in the last month was
52.9%, afflicting 18.7 million older adults in the US. Pain did not vary
across age groups (P=0.21) and this pattern remained unchanged
when accounting for cognitive performance, dementia, proxy-responses, and
residential care living status. Pain prevalence was higher in women and in older
adults with obesity, musculoskeletal conditions, and depressive symptoms
(P<0.001). The majority (74.9%) of older
adults with pain endorsed multiple sites of pain. Several measures of physical
capacity, including grip strength and lower extremity physical performance, were
associated with pain and multisite pain. For example, self-reported inability to
walk 3 blocks was 72% higher in participants with than without pain
[adjusted Prevalence Ratio=1.72 (95% Confidence Interval:
1.56–1.90)]. Participants with 1, 2, 3, and >4 sites of pain had
gait speeds that were 0.01, 0.03, 0.05, and 0.08 meters per second slower,
respectively, than older adults without pain, adjusting for disease burden and
other confounders (P<0.001). In summary, bothersome
pain in the last month was reported by half of the older adult population of the
US in 2011 and was strongly associated with decreased physical function.
pain; aging; geriatric assessment; locomotor activity; prevalence study
Mobility limitations are common and hazardous in community-dwelling older adults but are largely understudied, particularly regarding the role of the central nervous system (CNS). This has limited development of clearly defined pathophysiology, clinical terminology, and effective treatments. Understanding how changes in the CNS contribute to mobility limitations has the potential to inform future intervention studies.
A conference series was launched at the 2012 conference of the Gerontological Society of America in collaboration with the National Institute on Aging and the University of Pittsburgh. The overarching goal of the conference series is to facilitate the translation of research results into interventions that improve mobility for older adults.
Evidence from basic, clinical, and epidemiological studies supports the CNS as an important contributor to mobility limitations in older adults without overt neurologic disease. Three main goals for future work that emerged were as follows: (a) develop models of mobility limitations in older adults that differentiate aging from disease-related processes and that fully integrate CNS with musculoskeletal contributors; (b) quantify the contribution of the CNS to mobility loss in older adults in the absence of overt neurologic diseases; (c) promote cross-disciplinary collaboration to generate new ideas and address current methodological issues and barriers, including real-world mobility measures and life-course approaches.
In addition to greater cross-disciplinary research, there is a need for new approaches to training clinicians and investigators, which integrate concepts and methodologies from individual disciplines, focus on emerging methodologies, and prepare investigators to assess complex, multisystem associations.
Motor control; Central nervous system; Mobility.
Functional impairment, functional decline, and mobility loss are major public health problems in people with lower extremity peripheral artery disease (PAD). Few medical therapies significantly improve walking performance in PAD. We describe methods for the PROgenitor cell release Plus Exercise to improve functionaL performance in PAD (PROPEL) Study, a randomized controlled clinical trial designed to determine whether granulocyte-macrophage colony stimulating factor (GM-CSF) combined with supervised treadmill walking exercise improves six-minute walk distance more than GM-CSF alone, more than supervised treadmill exercise alone, and more than placebo plus attention control in participants with PAD, respectively. PROPEL Study participants are randomized to one of four arms in a 2 by 2 factorial design. The four study arms are GM-CSF plus supervised treadmill exercise, GM-CSF plus attention control, placebo plus supervised exercise therapy, or placebo plus attention control. The primary outcome is change in six-minute walk distance at 12-week follow-up. Secondary outcomes include change in brachial artery flow-mediated dilation (FMD), change in maximal treadmill walking time, and change in circulating CD34+ cells at 12-week follow-up. Outcomes are also measured at six-week and six-month follow-up. Results of the PROPEL Study will have important implications for understanding mechanisms of improving walking performance and preventing mobility loss in the large and growing number of men and women with PAD.
The relationship between menopausal characteristics and later life mortality is unclear. We tested the hypotheses that women with surgical menopause would have increased all-cause and cardiovascular mortality compared with women with natural menopause, and that women with earlier ages at natural or surgical menopause would have greater all-cause and cardiovascular mortality than women with later ages at menopause.
Women who participated in the Iowa cohort of the Established Populations for the Epidemiologic Study of the Elderly (n=1684) reported menopausal characteristics and potential confounding variables at baseline and were followed up for up to 24 years. Participants were aged 65 years or older at baseline and lived in rural areas. We used survival analysis to examine the relationships between menopausal characteristics and all-cause and cardiovascular mortality.
A total of 1477 women (87.7% of respondents) died during the study interval. Women with an age at natural menopause ≥55 years had increased all-cause and cardiovascular disease mortality compared with women who had natural menopause at younger ages. Type of menopause and age at surgical menopause were not related to mortality. These patterns persisted after adjustment for potential confounding variables.
Among an older group of women from a rural area of the United States, later age at natural menopause was related to increased all-cause and cardiovascular mortality. Monitoring the cardiovascular health of this group of older women may contribute to improved survival times.
To examine relationships between eight markers of inflammation (interleukin [IL]-6, IL-6 receptor [R], C-reactive protein [CRP], tumor necrosis factor [TNF]-α, TNF receptor 1[R1], TNFR2, IL-1 receptor antagonist, IL-18) and incident loss of ability to walk 400 m.
Prospective cohort study.
Older adults enrolled in the InvecchiareInChianti Study.
One thousand six community-dwelling participants aged 65+.
The eight inflammatory markers were measured at baseline, and an inflammation score was calculated based on the number of inflammatory markers for which the participant was in the highest quartile. Incidence of mobility disability was determined among participants able to walk 400 m at baseline. Logistic regression models were used to determine whether each of the inflammatory markers and the inflammation score predicts loss of the ability to walk 400 m at six-year follow-up.
After adjusting for covariates, individuals with aTNFR1 level in each of the top 3 quartiles (Q2, 3, 4) were more likely to be unable to walk 400 m at follow-up compared to those with TNFR1 levels in Q1. When adjusting for the same covariates, participants with an inflammation score of 3 or 4 were more likely to become unable to complete the 400 m walk at follow-up compared to participants with a score of 0.
These results bring additional evidence to the notion that inflammation is implicated in the mechanisms that cause incident mobility disability and suggest that a combined measure of inflammatory markers may improve our prediction of functional prognosis.
inflammation; mobility; 400 m walk; functional limitation; aging
White matter hyperintensity (WMH) confers increased mortality risk in patients with cardiovascular diseases. However, little is known about differences in survival times among adults 65 years and older who have WMH and live in the community. To characterize the factors that may reduce mortality risk in the presence of WMH, measures of race, sex, ApoE4, neuroimaging, cardiometabolic, physiological and psychosocial characteristics were examined, with a particular focus on information processing as measured by the Digit Symbol Substitution Test(DSST).
Cox-proportional models were used to estimate mortality risks in a cohort of 3513 adults (74.8years, 58%women, 84%white) with WMH (0–9 points), DSST (0–90 points), risk factor assessment in 1992–94 and data on mortality and incident stroke to 2009 (median follow-up [range]:14.2[0.5–18.1]years).
WMH predicted a 48% greater mortality risk (age-adjusted hazard ratio (HR)[95% confidence interval(CI)] for WMH>3 points=1.48[1.35–1.62]). This association was attenuated after adjustment for DSST (HR[CI]: 1.38[1.27–1.51]) or lacunar infarcts (HR[CI]: 1.37[1.25,1.50]) but not after adjustment for other factors. The interaction between DSST and WMH was significant (p=0.011). In fully adjusted models stratified by WMH>3, participants with DSST>median had a 34% lower mortality risk among those with WMH>3 (n=532/1217) and a 28% lower mortality risk among those with WMH<3 (n=1364/2296), compared to participants with DSST
WMH is associated with increased long-term mortality risk in community-dwelling adults aged 65 and older. The increased risk is attenuated for those with higher DSST. Assessment of cognitive function with DSST may improve risk stratification of individuals with WMH.
mortality; information processing; white matter hyperintensity
This study examines the associations between lifecourse adversity and physical performance in old age in different societies of North and South America and Europe.
We used data from the baseline survey of the International Study of Mobility in Aging, conducted in: Kingston (Canada), Saint-Hyacinthe (Canada), Natal (Brazil), Manizales (Colombia) and Tirana (Albania). The study population was composed of community dwelling people between 65 and 74 years of age, recruiting 200 men and 200 women at each site. Physical Performance was assessed with the Short Physical Performance Battery (SPPB). Economic and social adversity was estimated from childhood adverse events, low education, semi-skilled occupations during adulthood and living alone and insufficient income in old age.
A total of 1995 people were assessed. Low physical performance was associated with childhood social and economic adversity, semi-skilled occupations, living alone and insufficient income. Physical performance was lower in participants living in Colombia, Brazil and Albania than in Canada counterparts, despite adjustment for lifecourse adversity, age and sex.
We show evidence of the early origins of social and economic inequalities in physical performance during old age in distinct populations and for the independent and cumulative disadvantage of low socioeconomic status during adulthood and poverty and living alone in later life.
Higher intake of fruits and vegetables appears to protect against inflammation, poor physical performance, and disability, but their relationship with muscle strength is unclear. We examined the association between total plasma carotenoids, an indicator of fruit and vegetable intake, and changes in muscle strength over a 6-year follow-up in the participants aged 65 years and older in the InCHIANTI study, a population-based study in Tuscany, Italy.
Plasma carotenoids were measured at enrollment (1998–2000). Hip, knee and grip strength were measured at enrollment and 6 years later (2004–2006) in 628 of the 948 participants evaluated at baseline. Poor muscle strength was defined as the lowest sex-specific quartile of hip, knee and grip strength at enrollment. The main outcome was poor muscle strength at the six-year follow-up visit among those originally in the upper three quartiles of strength at enrollment.
Overall, 24.9% (110/441), 25.0% (111/444) and 24.9% (118/474) participants developed poor hip, knee and grip strength, respectively. After adjusting for potential confounders, participants in the lowest vs. the highest quartile of total plasma carotenoids at enrollment were at higher risk of developing poor hip (O.R. 2.25, 95% C.I. 1.13–4.48, P = 0.02), knee (O.R. 2.12, 95% C.I. 1.08–4.09, P = 0.03) and grip (O.R. 1.85, 95% C.I. 0.95–3.61, P = 0.07) muscle strength at the six-year follow-up visit.
These findings suggest that older community-dwelling adults with lower plasma carotenoids levels, a marker of poor fruit and vegetable intake, are at a higher risk of decline in skeletal muscle strength over time.
carotenoids; InCHIANTI study; fruit; vegetable; sarcopenia
Results 1-25 (205)
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