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1.  Lifestyle Interventions and Independence for Elders Study: Recruitment and Baseline Characteristics 
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.
PMCID: PMC3814232  PMID: 23716501
Mobile disability; Older adults; Physical activity; Minority recruitment; Randomized controlled trial.
2.  The Cooperative Lifestyle Intervention Program-II (CLIP-II): Design and Methods 
Contemporary clinical trials  2013;36(2):10.1016/j.cct.2013.08.006.
A complication of cardiovascular disease (CVD) and the metabolic syndrome (MetS) among older adults is loss of mobility. The American Heart Association has identified weight management as a core component of secondary prevention programs for CVD and is an important risk factor for physical disability. The American Society for Nutrition and the Obesity Society have highlighted the need for long-term randomized clinical trials to evaluate the independent and additive effects of diet-induced weight loss (WL) and physical activity in older persons on outcomes such as mobility, muscle function, and obesity related diseases.
Here we describe the rationale, design, and methods of a translational study, the Cooperative Lifestyle Intervention Program-II (CLIP-II).
CLIP-II will randomize 252 obese, older adults with CVD or MetS to a weight loss only treatment (WL), aerobic exercise training (AT)+WL, or resistance exercise training (RT)+WL for 18 months. The dual primary outcomes are mobility and knee extensor strength. The interventions will be delivered by YMCA community partners with our staff as trainers and advisers. This study will provide the first large scale trial to evaluate the effects of diet-induced WL on mobility in obese, older adults with CVD or MetS as compared to WL combined with two different modes of physical activity (AT and RT). Because uncertainty exists about the best approach for promoting WL in older adults due to concerns with the loss of lean mass, the design also permits a contrast between AT+WL and RT+WL on muscle strength.
PMCID: PMC3843993  PMID: 23974035
translational science; exercise; older adults; obesity; weight loss; physical activity
3.  Resistance Training and Pioglitazone Lead to Improvements in Muscle Power During Voluntary Weight Loss in Older Adults 
The prevalence of obesity in older adults is increasing but concerns exist about the effect of weight loss on muscle function. Demonstrating that muscle strength and power are not adversely affected during “intentional” weight loss in older adults is important given the wide-ranging negative health effects of excess adiposity.
Participants (N = 88; age = 70.6 ± 3.6 years; body mass index = 32.8 ± 4.5kg/m2) were randomly assigned to one of four intervention groups: pioglitazone or placebo and resistance training (RT) or no RT, while undergoing intentional weight loss via a hypocaloric diet. Outcomes were leg press power and isometric knee extensor strength. Analysis of covariance, controlling for baseline values, compared follow-up means of power and strength according to randomized groups.
Participants lost an average of 6.6% of initial body mass, and significant declines were observed in fat mass, lean body mass, and appendicular lean body mass. Compared with women not randomized to RT, women randomized to RT had significant improvements in leg press power (p < .001) but not in knee extensor strength (p = 0.12). No significant differences between groups in change in power or strength from baseline were detected in men (both p > .25). A significant pioglitazone-by-RT interaction for leg press power was detected in women (p = .006) but not in men (p = .88).
In older overweight and obese adults, a hypocaloric weight loss intervention led to significant declines in lean body mass and appendicular lean body mass. However, in women assigned to RT, leg power significantly improved following the intervention, and muscle strength or power was not adversely effected in the other groups. Pioglitazone potentiated the effect of RT on muscle power in women but not in men; mechanisms underlying this sex effect remain to be determined.
PMCID: PMC3693600  PMID: 23292287
Obesity; Resistance training; Muscle strength; Muscle power; Voluntary weight loss.
4.  Lower Extremity Muscle Function After Strength or Power Training in Older Adults 
It is unclear whether strength training (ST) or power training (PT) is the more effective intervention at improving muscle strength and power and physical function in older adults. The authors compared the effects of lower extremity PT with those of ST on muscle strength and power in 45 older adults (74.8 ± 5.7 yr) with self-reported difficulty in common daily activities. Participants were randomized to 1 of 3 treatment groups: PT, ST, or wait-list control. PT and ST trained 3 times/wk for 12 wk using knee-extension (KE) and leg-press (LP) machines at ~70% of 1-repetition maximum (1RM). For PT, the concentric phase of the KE and LP was completed “as fast as possible,” whereas for ST the concentric phase was 2–3 s. Both PT and ST paused briefly at the midpoint of the movement and completed the eccentric phase of the movement in 2–3 s. PT and ST groups showed significant improvements in KE and LP 1RM compared with the control group. Maximum KE and LP power increased approximately twofold in PT compared with ST. At 12 wk, compared with control, maximum KE and LP power were significantly increased for the PT group but not for the ST group. In older adults with compromised function, PT leads to similar increases in strength and larger increases in power than ST.
PMCID: PMC4318571  PMID: 19940322
aging; resistance training; disability; physical function
5.  The effects of strength and power training on single-step balance recovery in older adults: a preliminary study 
Improving muscle strength and power may mitigate the effects of sarcopenia, but it is unknown if this improves an older adult’s ability to recover from a large postural perturbation. Forward tripping is prevalent in older adults and lateral falls are important due to risk of hip fracture. We used a forward and a lateral single-step balance recovery task to examine the effects of strength training (ST) or power (PT) training on single-step balance recovery in older adults. Twenty older adults (70.8±4.4 years, eleven male) were randomly assigned to either a 6-week (three times/week) lower extremity ST or PT intervention. Maximum forward (FLeanmax) and lateral (LLeanmax) lean angle and strength and power in knee extension and leg press were assessed at baseline and follow-up. Fifteen participants completed the study (ST =7, PT =8). Least squares means (95% CI) for ΔFLeanmax (ST: +4.1° [0.7, 7.5]; PT: +0.6° [−2.5, 3.8]) and ΔLLeanmax (ST: +2.2° [0.4, 4.1]; PT: +2.6° [0.9, 4.4]) indicated no differences between groups following training. In exploratory post hoc analyses collapsed by group, ΔFLeanmax was +2.4° (0.1, 4.7) and ΔLLeanmax was +2.4° (1.2, 3.6). These improvements on the balance recovery tasks ranged from ~15%–30%. The results of this preliminary study suggest that resistance training may improve balance recovery performance, and that, in this small sample, PT did not lead to larger improvements in single-step balance recovery compared to ST.
PMCID: PMC4000185  PMID: 24790422
resistance exercise; falls; muscle strength; muscle power; exercise intervention; randomized trial
6.  Resistance exercise performance variability at submaximal intensities in older and younger adults 
We assessed the variability in the number of repetitions completed at submaximal loads in three resistance tasks in older (N=32, 16 female, 74.3±5.4 years) and younger (N=16, 8 female, 22.8±1.8 years) men and women. One repetition maximum (1RM) was determined on two separate visits on three tasks: leg press (LP), leg extension (LE), and bicep curl (BC). Subjects then completed repetitions to failure on each of the three tasks during two visits, a minimum of 48 hours apart, at either 60% 1RM or 80% 1RM. High reliability for all 1RM assessments was observed. Greater muscular strength was observed in younger compared to older men and women on all tasks (P<0.05). At both 60% and 80% 1RM, considerable interindividual variability was observed in the number of repetitions completed. However, the average number of repetitions completed by younger and older men and women at 60% and 80% 1RM in each of the three tasks was similar, with the only significant difference occurring between younger and older men at 80% 1RM on the leg press (P=0.0258). We did not observe any abnormal blood pressure responses to either the 1RM testing or maximal repetition testing sessions. Considerable interindividual variability was observed in the number of repetitions completed by younger and older men and women at relative intensities typical of resistance training programs. Practitioners should give consideration to individual variability when attempting to maximize the benefits of resistance training.
PMCID: PMC3900316  PMID: 24465127
resistance exercise; exercise prescription; relative intensity; reliability; older adults; blood pressure
7.  The MAT-sf: Clinical Relevance and Validity 
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.
PMCID: PMC3814234  PMID: 23685766
Mobility; Geriatric assessment; Physical function; MAT-sf
8.  Upper Extremity Muscle Volumes and Functional Strength After Resistance Training in Older Adults 
Aging leads to a decline in strength and an associated loss of independence. The authors examined changes in muscle volume, maximum isometric joint moment, functional strength, and 1-repetition maximum (1RM) after resistance training (RT) in the upper extremity of older adults. They evaluated isometric joint moment and muscle volume as predictors of functional strength. Sixteen healthy older adults (average age 75 ± 4.3 yr) were randomized to a 6-wk upper extremity RT program or control group. The RT group increased 1RM significantly (p < .01 for all exercises). Compared with controls, randomization to RT led to greater functional pulling strength (p = .003), isometric shoulder-adduction moment (p = .041), elbow-flexor volume (p = .017), and shoulder-adductor volume (p = .009). Shoulder-muscle volumes and isometric moments were good predictors of functional strength. The authors conclude that shoulder strength is an important factor for performing functional reaching and pulling tasks and a key target for upper extremity RT interventions.
PMCID: PMC4153379  PMID: 22952203
biomechanics; isometric joint moment; reaching; aging
9.  Effect of an 18 month physical activity and weight loss intervention on body composition in overweight and obese older adults 
Obesity (Silver Spring, Md.)  2013;22(2):325-331.
Our primary objective was to determine the long-term effects of physical activity (PA) and weight loss (WL) on body composition in overweight/obese older adults. Secondarily, we evaluated the association between change in body mass and composition on change in several cardiometabolic risk factors and mobility.
Design and Methods
288 older (X±SD: 67.0±4.8 years), overweight/obese (BMI 32.8±3.8 kg/m2) men and women participated in this 18 month randomized, controlled trial. Treatment groups included PA+WL (n=98), PA-only (n=97), and a successful aging (SA) health education control (n=93). DXA-acquired body composition measures (total body fat and lean mass), conventional biomarkers of cardiometabolic risk, and 400-m walk time were obtained at baseline and 18 months.
Fat mass was significantly reduced from (X±SE) 36.5±8.9 kg to 31.7±9.0 kg in the PA+WL group (p<0.01), but remained unchanged from baseline in the PA-only (−0.8±3.8 kg) and SA (−0.0±3.9 kg) groups. Lean mass losses were three times greater in the PA+WL group compared to PA-only or SA groups (−2.5±2.8 kg vs. −0.7±2.2 kg or −0.8±2.4 kg, respectively; p<0.01); yet due to a larger decrease in fat mass, percent lean mass was significantly increased over baseline in the PA+WL group (2.1%±2.6%; p<0.01). Fat mass loss was primarily responsible for WL-associated improvements in cardiometabolic risk factors, while reduction in body weight, regardless of compartment, was significantly associated with improved mobility.
This 18 month PA+WL program resulted in a significant reduction in percent body fat with a concomitant increase in percent body lean mass. Shifts in body weight and composition were associated with favorable changes in clinical parameters of cardiometabolic risk and mobility. Moderate PA without WL had no effect on body composition.
PMCID: PMC3880399  PMID: 23963786
weight loss; physical activity; body composition; cardiometabolic risk; functional decline; aging
10.  Muscle Strength and BMI as Predictors of Major Mobility Disability in the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) 
Muscle weakness and obesity are two significant threats to mobility facing the increasing number of older adults. To date, there are no studies that have examined the association of strength and body mass index (BMI) on event rates on a widely used performance measure of major mobility disability.
This study was a secondary analysis of a randomized controlled trial in which sedentary functionally limited participants (70–89 years, Short Physical Performance Battery ≤ 9) who were able to complete a 400-m walk test at baseline were randomized to a physical activity or health education intervention and reassessed for major mobility disability every 6 months for up to 18 months. We evaluated whether baseline grip strength and BMI predicted failure to complete the 400-m walk test in 15 minutes or less (major mobility disability).
Among N = 406 participants with baseline measures, lower grip strength was associated with an increased risk for developing major mobility disability, with and without covariate adjustment (p < .01): The hazard ratio (95% confidence interval) for the lowest versus high sex-specific quartile of grip strength was 6.11 (2.24–16.66). We observed a U-shaped relationship between baseline BMI and the risk of developing major mobility disability, such that the risk for participants with a BMI of 25–29 kg/m2 was approximately half that of participants with BMI less than 25 or 30 kg/m2 or more (p = .04 in fully adjusted analyses).
Our data highlight the importance of muscle weakness, low BMI, and obesity as risk factors for major mobility disability in older adults. Being overweight may be protective for major mobility disability.
PMCID: PMC3210962  PMID: 21975090
Physical disability; Physical activity; Older adults
11.  Using Video Animation to Assess Mobility in Older Adults 
Although the importance of the context of task performance in the assessment of mobility in older adults is generally understood, there is little empirical evidence that demonstrates how sensitive older adults are to subtle changes in task demands. Thus, we developed a novel approach to examine this issue.
We collected item response data to 81 animated video clips, where various mobility-related tasks were modified in a systematic fashion to manipulate task difficulty.
The participants (N = 234), 166 women and 68 men, had an average age of 81.9 years and a variety of comorbidities. Histograms of item responses revealed dramatic and systematic effects on older adults’ self-reported ability when varying walking speed, use of a handrail during ascent and descent of stairs, walking at different speeds outdoors over uneven terrain, and carrying an object. For example, there was almost a threefold increase in reporting the inability to walk at the fast speed compared with the slow speed for a minute or less, and twice as many participants reported the inability to walk at the fast speed outdoors over uneven terrain compared with indoors.
The data provide clear evidence that varying the contextual features and demands of a simple task such as stair climbing has a significant impact on older adults’ self-reporting of ability related to mobility. More work is needed on the psychometric properties of such assessments and to determine if this methodology has conceptual and clinical relevance in studying mobility disability.
PMCID: PMC3021373  PMID: 21127192
Mobility; Aging; Disability; Physical function
12.  Physical Activity Increases Gains in and Prevents Loss of Physical Function: Results From the Lifestyle Interventions and Independence for Elders Pilot Study 
Physical activity (PA) appears to have a positive effect on physical function, however, studies have not examined multiple indices of physical function jointly nor have they conceptualized physical functioning as a state rather than a trait.
About 424 men and women aged 70–89 were randomly assigned to complete a PA or a successful aging (SA) education program. Balance, gait speed, chair stand performance, grip strength, and time to complete the 400-m walk were assessed at baseline and at 6 and 12 months. Using hidden Markov model, empiric states of physical functioning were derived based on these performance measures of balance, strength, and mobility. Rates of gain and loss in physical function were compared between PA and SA.
Eight states of disability were identified and condensed into four clinically relevant states. State 1 represented mild disability with physical functioning, states 2 and 3 were considered intermediate states of disability, and state 4 severe disability. About 30.1% of all participants changed states at 6 months, 24.1% at 12 months, and 11.0% at both time points. The PA group was more likely to regain or sustain functioning and less likely to lose functioning when compared with SA. For example, PA participants were 20% more likely than the SA participants to remain in state 1.
PA appears to have a favorable effect on the dynamics of physical functioning in older adults.
PMCID: PMC3593616  PMID: 22987794
Older adults; Physical activity; Randomized controlled trial; Physical functioning; Transitional states.
13.  Lower Extremity Strength and Power Are Associated With 400-Meter Walk Time in Older Adults: The InCHIANTI Study 
It has been suggested that lower extremity muscle power is more important for physical function in older adults compared to strength, and that there is a nonlinear relationship between power or strength and physical function that might be indicative of a threshold above which the association between muscle function and physical function is no longer evident. This study examined the association between lower extremity strength or power with the time to complete a 400-meter walk, and attempted to identify thresholds within the relationship.
A cross-sectional analysis of a sample of 384 females and 336 males aged ≥ 65 years from the InCHIANTI study (“Invecchiare in Chianti,” i.e., Aging in the Chianti Area) was conducted. Measures included 400-meter walk time, lower extremity strength and power, comorbidities, and sociodemographic variables (age, gender, height, education, cognitive function, depression).
Linear regression models showed that both lower extremity strength and power were significant predictors of 400-meter walk time, although power explained marginally more of the variance in 400-meter walk time. Quadratic models of lower extremity strength and power fit the data slightly better than the linear models. Regardless of gender, comorbidities, or normalization scheme for strength and power, the curvilinear form of the relationship between strength or power and 400-meter walk time remained the same.
Lower extremity muscle strength and power are both important predictors of the 400-meter walk time. Although curvilinear relationships existed between muscle strength and power and the 400-meter walk time, the data do not indicate a clear threshold for either strength or power above which the performance in the 400-meter walk test plateaus.
PMCID: PMC2668162  PMID: 17167161
14.  Kinematics of gait in Golden Retriever Muscular Dystrophy 
Neuromuscular disorders : NMD  2009;20(1):16-20.
The goal of this study was to quantify the two-dimensional kinematics of pathologic gait during overground walking at a self-selected speed at the stifle (knee) and hock (ankle) joints in six Golden Retriever Muscular Dystrophy (GRMD) dogs and six carrier littermates (controls). We found that GRMD dogs walked significantly slower than controls (p < 0.01). At the stifle joint, both groups displayed similar ROM (range of motion), but compared to controls, GRMD dogs walked with the stifle joint relatively more extended. At the hock joint, GRMD dogs displayed less ROM (range of motion) and walked with the joint relatively less flexed compared to controls. We controlled for gait speed in all analyses, so the differences we observed in joint kinematics between groups cannot be attributed solely to the slower walking speed of the GRMD dogs. This is the first kinematic study of gait in the GRMD dog, an important step in using this model in pre-clinical trials.
PMCID: PMC3777817  PMID: 19932618
Muscular dystrophy; Locomotion; Biomechanics; Canine; Physical function
15.  Promoting physical activity for elders with compromised function: the lifestyle Interventions and Independence for elders (LIFE) study physical activity intervention 
The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase III randomized controlled clinical trial ( identifier: NCT01072500) that will provide definitive evidence regarding the effect of physical activity (PA) on major mobility disability in older adults (70–89 years old) who have compromised physical function. This paper describes the methods employed in the delivery of the LIFE Study PA intervention, providing insight into how we promoted adherence and monitored the fidelity of treatment. Data are presented on participants’ motives and self-perceptions at the onset of the trial along with accelerometry data on patterns of PA during exercise training. Prior to the onset of training, 31.4% of participants noted slight conflict with being able to meet the demands of the program and 6.4% indicated that the degree of conflict would be moderate. Accelerometry data collected during PA training revealed that the average intensity – 1,555 counts/minute for men and 1,237 counts/minute for women – was well below the cutoff point used to classify exercise as being of moderate intensity or higher for adults. Also, a sizable subgroup required one or more rest stops. These data illustrate that it is not feasible to have a single exercise prescription for older adults with compromised function. Moreover, the concept of what constitutes “moderate” exercise or an appropriate volume of work is dictated by the physical capacities of each individual and the level of comfort/stability in actually executing a specific prescription.
PMCID: PMC3775623  PMID: 24049442
aging; accelerometry; physical disability; compromised physical function; older adults
16.  Design and implementation of the mobility assessment tool: software description 
In previous work, we described the development of an 81-item video-animated tool for assessing mobility. In response to criticism levied during a pilot study of this tool, we sought to develop a new version built upon a flexible framework for designing and administering the instrument.
Rather than constructing a self-contained software application with a hard-coded instrument, we designed an XML schema capable of describing a variety of psychometric instruments. The new version of our video-animated assessment tool was then defined fully within the context of a compliant XML document. Two software applications—one built in Java, the other in Objective-C for the Apple iPad—were then built that could present the instrument described in the XML document and collect participants’ responses. Separating the instrument’s definition from the software application implementing it allowed for rapid iteration and easy, reliable definition of variations.
Defining instruments in a software-independent XML document simplifies the process of defining instruments and variations and allows a single instrument to be deployed on as many platforms as there are software applications capable of interpreting the instrument, thereby broadening the potential target audience for the instrument. Continued work will be done to further specify and refine this type of instrument specification with a focus on spurring adoption by researchers in gerontology and geriatric medicine.
PMCID: PMC3729603  PMID: 23879716
17.  Relationship of physical function to vastus lateralis capillary density and metabolic enzyme activity in elderly men and women 
Background and aims
There are no data showing whether or not age-related declines in physical function are related to in vitro properties of human skeletal muscle. The purpose of this study was to determine whether physical function is independently associated with histologic and metabolic properties of skeletal muscle in elderly adults.
The study was a cross-sectional observational study of 39 sedentary, older (60–85 yrs) men and women. A needle biopsy of the vastus lateralis for assessment of muscle fiber type, fiber area, capillary density and citrate synthase and aldolase activities was performed. Physical function tests included the Short Physical Performance Battery (balance, walking speed, and chair rise time), as well as self-reported disability.
Total fiber area (R=−0.41, p=0.02), number of Type II fibers (R=−0.33, p=0.05), and aldolase activity (R=−0.54, p=0.01) were inversely related to age. Persons who reported greater difficulty with daily activities had lower capillary density (R=−0.51, p=0.03) and lower citrate synthase activity (R=−0.66, p=0.03). Walking speed was directly related to fiber area (R=0.40, p=0.02), capillary density (R=0.39, p=0.03), citrate synthase (R=0.45, p=0.03) and aldolase (R=0.55, p<0.01) activities, even after adjustment for age, BMI and disease status.
In older adults, skeletal muscle capillary density and metabolic enzymatic activity are independent predictors of lower extremity physical function.
PMCID: PMC3665340  PMID: 18852542
Capillary density; enzyme activity; physical function; skeletal muscle
18.  Plasma nitrate and nitrite are increased by a high nitrate supplement, but not by high nitrate foods in older adults 
Little is known about the effect of dietary nitrate on the nitrate/nitrite/NO (nitric oxide) cycle in older adults. We examined the effect of a 3-day control diet vs. high nitrate diet, with and without a high nitrate supplement (beetroot juice), on plasma nitrate and nitrite kinetics, and blood pressure using a randomized four period cross-over controlled design. We hypothesized that the high nitrate diet would show higher levels of plasma nitrate/nitrite and blood pressure compared to the control diet, which would be potentiated by the supplement. Participants were eight normotensive older men and women (5 female, 3 male, 72.5±4.7 yrs) with no overt disease or medications that affect NO metabolism. Plasma nitrate and nitrite levels and blood pressure were measured prior to and hourly for 3 hours after each meal. The mean daily changes in plasma nitrate and nitrite were significantly different from baseline for both control diet+supplement (p<0.001 and =0.017 for nitrate and nitrite, respectively) and high nitrate diet+supplement (p=0.001 and 0.002), but not for control diet (p=0.713 and 0.741) or high nitrate diet (p=0.852 and 0.500). Blood pressure decreased from the morning baseline measure to the three 2 hr post-meal follow-up time-points for all treatments, but there was no main effect for treatment. In healthy older adults, a high nitrate supplement consumed at breakfast elevated plasma nitrate and nitrite levels throughout the day. This observation may have practical utility for the timing of intake of a nitrate supplement with physical activity for older adults with vascular dysfunction.
PMCID: PMC3319660  PMID: 22464802
older adult; beetroot juice; nitric oxide; cross-over controlled
19.  Plasma nitrite response in older women to a physical function test 
Background and aims
Nitric oxide (NO) may play a critical role in facilitating the delivery of blood to active skeletal muscle, ultimately impacting functional health in older adults. Plasma nitrite is a useful marker of vascular NO bioavailability. The aim of the current investigation was to examine the effect of a widely used physical function test on plasma nitrite concentrations in older adults.
Venous blood was drawn before, immediately following, and 10 minutes following the completion of a 400-m walk test. Blood samples were added to heparin and frozen for subsequent analysis of nitrite levels using chemiluminescence.
Twenty six (79±4 yrs) women participated in this study. Plasma nitrite levels decreased approximately 22% from baseline following a 400-m walk. Percent change in plasma nitrite was related to walking speed (r=−0.550, p=0.004).
These data suggest an alteration in plasma nitrite concentration following a functional test which may impact functional health.
PMCID: PMC3562699  PMID: 20009500
Acute exercise; nitric oxide; plasma nitrite; 400 meter walk
20.  Characterizing upper limb muscle volume and strength in older adults: A comparison with young adults 
Journal of biomechanics  2011;45(2):334-341.
Aging is associated with loss of muscle volume (MV) and force leading to difficulties with activities of daily living. However, the relationship between upper limb MV and joint strength has not been characterized for older adults. Quantifying this relationship may help our understanding of the functional upper limb declines older adults experience. Our objective was to assess the relationship between upper limb MV and maximal isometric joint moment-generating capacity (IJM) in a single cohort of healthy older adults (age≥65 years) for 6 major functional groups (32 muscles). MV was determined from MRI for 18 participants (75.1±4.3 years). IJM at the shoulder (abduction/adduction), elbow (flexion/extension), and wrist (flexion/extension) was measured. MV and IJM measurements were compared to previous reports for young adults (28.6±4.5 years). On average older adults had 16.5% less total upper limb MV compared to young adults. Additionally, older adult wrist extensors composed a significantly increased percentage of upper limb MV. Older adult IJM was reduced across all joints, with significant differences for shoulder abductors (p<0.0001), adductors (p=0.01), and wrist flexors (p<0.0001). Young adults were strongest at the shoulder, which was not the case for older adults. In older adults, 40.6% of the variation in IJM was accounted for by MV changes (p≤0.027), compared to 81.0% in young adults. We conclude that for older adults, MV and IJM are, on average, reduced but the significant linear relationship between MV and IJM is maintained. These results suggest that older adult MV and IJM cannot be simply scaled from young adults.
PMCID: PMC3246044  PMID: 22047782
Muscle volume; Strength; Upper limb; Aging; Joint moment
21.  A permutation testing framework to compare groups of brain networks 
Brain network analyses have moved to the forefront of neuroimaging research over the last decade. However, methods for statistically comparing groups of networks have lagged behind. These comparisons have great appeal for researchers interested in gaining further insight into complex brain function and how it changes across different mental states and disease conditions. Current comparison approaches generally either rely on a summary metric or on mass-univariate nodal or edge-based comparisons that ignore the inherent topological properties of the network, yielding little power and failing to make network level comparisons. Gleaning deeper insights into normal and abnormal changes in complex brain function demands methods that take advantage of the wealth of data present in an entire brain network. Here we propose a permutation testing framework that allows comparing groups of networks while incorporating topological features inherent in each individual network. We validate our approach using simulated data with known group differences. We then apply the method to functional brain networks derived from fMRI data.
PMCID: PMC3839047  PMID: 24324431
graph theory; connectivity; fMRI; small-world; neuroimaging; Jaccard; Kolmogorov-Smirnov
22.  Change in 25-Hydroxyvitamin D and Physical Performance in Older Adults 
Vitamin D deficiency is common among older adults and is associated with poor physical performance; however, studies examining longitudinal changes in 25-hydroxyvitamin D (25[OH]D) and physical performance are lacking. We examined the association between 25(OH)D and physical performance over 12 months in older adults participating in the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P), a multicenter physical activity intervention trial.
Plasma 25(OH)D and physical performance, assessed by the short physical performance battery (SPPB) and 400-m walk test, were measured at baseline, 6-month, and 12-month follow-up in community-dwelling adults aged 70–89 years at risk for disability (n = 368). Mixed models were used to examine the association between 25(OH)D and physical performance adjusting for demographics, intervention group, season, body mass index, and physical activity.
One half of the participants were vitamin D deficient (25[OH]D < 20 ng/mL) at baseline. In cross-sectional analyses, vitamin D deficiency was associated with lower SPPB scores and slower 400-m walk speeds (mean difference [SE]: 0.35 [0.16], p = .03 and 0.04 [0.02] m/s, p = .01, respectively). Although baseline 25(OH)D status was not significantly associated with change in physical performance over 12 months, individuals who were vitamin D deficient at baseline but no longer deficient at follow-up had significant improvements in SPPB scores (mean difference [SE]: 0.55 [0.22], p = .01) compared with those whose 25(OH)D status remained the same.
Increases in 25(OH)D to greater than or equal to 20 ng/mL were associated with clinically significant improvements in physical performance among older adults.
PMCID: PMC3055282  PMID: 21325343
Vitamin D; Physical performance; Aging
23.  The Effect of Pioglitazone and Resistance Training on Body Composition in Older Men and Women Undergoing Hypocaloric Weight Loss 
Obesity (Silver Spring, Md.)  2011;19(8):1636-1646.
Age-related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPARγ-agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65–79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m2) and women (n = 40, BMI = 33.3 ± 4.9 kg/m2) during weight loss. All participants underwent a 16-week hypocaloric weight-loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow-up using computed tomography (CT). Lean mass was measured using dual X-ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (−1,160 vs. −647 cm3, P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (−104 vs. −298 cm3, P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: −43 vs. −88 cm3, P = 0.005; women: −34 vs. −59 cm3, P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.
PMCID: PMC3091968  PMID: 21233810
24.  Obesity, Intentional Weight Loss, and Physical Disability in Older Adults 
We examine obesity, intentional weight loss, and physical disability in older adults. Based on prospective epidemiological studies, BMI exhibits a curvilinear relationship with physical disability; there appears to be some protective effect associated with older adults being overweight. Whereas the greatest risk for physical disability occurs in older adults who are ≥class II obesity, the effects of obesity on physical disability appears to be moderated by both sex and race. Obesity at age 30 constitutes a greater risk for disability later in life than when obesity develops at age 50 or later; however, physical activity may buffer the adverse effects obesity has on late life physical disability. Data from a limited number of randomized clinical trials (RCTs) reinforce the important role that physical activity plays in weight loss programs for older adults. Furthermore, short-term studies have found that resistance training may be particularly beneficial in these programs since this mode of exercise attenuates the loss of fat-free mass during caloric restriction. Multi-year RCTs are needed to examine whether weight loss can alter the course of physical disablement in aging and to determine the long-term feasibility and effects of combining resistance exercise with weight loss in older adults.
PMCID: PMC2888667  PMID: 19922431
Body-mass index (BMI); physical function; elderly; physical activity; exercise
25.  Development and Validation of a Video-Animated Tool for Assessing Mobility 
Existing self-report measures of mobility ignore important contextual features of movement and require respondents to make complex judgments about specific tasks. Thus, we describe the development and validation of a short form (sf) video-animated tool for assessing mobility, the Mobility Assessment Tool—MAT-sf.
This study involves cross-sectional and longitudinal analyses examining the measurement properties of the MAT-sf. The MAT-sf consists of 10 animated video clips that assess respondents’ level of proficiency in performing each task. The main outcome measures used for validation included the Pepper Assessment Tool for Disability (PAT-D), the Short Physical Performance Battery (SPPB), and 400-m walk test.
Participants (n = 234), 166 women and 68 men, had an average age of 81.9 years and a variety of comorbidities with 65.4% having high blood pressure. An average SPPB score of 8.6 (range 2–12) suggests that the study sample had evidence of compromised physical function but was quite heterogeneous. The MAT-sf had good content validity, excellent test–retest reliability (r = .93), and criterion-related validity with the PAT-D. Moreover, the MAT-sf added considerable variance to the prediction of both SPPB scores and 400-m gait speed over and above the PAT-D mobility subscale. The MAT-sf also discriminated between older adults who completed or failed the 400-m walk test.
The MAT-sf is an innovative psychometrically sound measure of mobility. It has utility in epidemiological studies, translational science, and clinical practice.
PMCID: PMC2869532  PMID: 20403946
Mobility; Aging; Measurement; Disability

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