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.
aging; resistance training; disability; physical function
A major desire of individuals with spinal cord injury (SCI) is the ability to maintain a stable trunk while in a seated position. Such stability is invaluable during many activities of daily living (ADL) such as regular work in the home and office environments, wheelchair propulsion and driving a vehicle. Functional neuromuscular stimulation (FNS) has the ability to restore function to paralyzed muscles by application of measured low-level currents to the nerves serving those muscles.
A feedback control system for maintaining seated balance under external perturbations was designed and tested in individuals with thoracic and cervical level spinal cord injuries. The control system relied on a signal related to the tilt of the trunk from the vertical position (which varied between 1.0 ≡ erect posture and 0.0 ≡ most forward flexed posture) derived from a sensor fixed to the sternum to activate the user’s own hip and trunk extensor muscles via an implanted neuroprosthesis. A proportional-derivative controller modulated stimulation between trunk tilt values indicating deviation from the erect posture and maximum desired forward flexion. Tests were carried out with external perturbation forces set at 35%, 40% and 45% body-weight (BW) and maximal forward trunk tilt flexion thresholds set at 0.85, 0.75 and 0.70.
Preliminary tests in a case series of five subjects show that the controller could maintain trunk stability in the sagittal plane for perturbations up to 45% of body weight and for flexion thresholds as low as 0.7. The mean settling time varied across subjects from 0.5(±0.4) and 2.0 (±1.1) seconds. Mean response time of the feedback control system varied from 393(±38) ms and 536(±84) ms across the cohort.
The results show the high potential for robust control of seated balance against nominal perturbations in individuals with spinal cord injury and indicates that trunk control with FNS is a promising intervention for individuals with SCI.
Trunk control; Seated balance; Functional Neuromuscular Stimulation (FNS); Spinal cord injury; Feedback control; Rehabilitation
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.
Depression has been identified as a risk factor for dementia among patients with Type 2 diabetes mellitus but the cognitive domains and patient groups most affected have not been identified.
To determine whether comorbid depression in patients with type 2 diabetes accelerates cognitive decline.
A 40-month cohort study of participants in the ACCORD-MIND trial
52 clinics organized into 6 clinical networks across the US and Canada.
2977 participants with Type 2 diabetes at high-risk for cardiovascular events
Main Outcome Measures
The Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), and the modified Stroop test were used to assess cognition. The Physician’s Health Questionnaire-9 (PHQ-9) was used to assess depression. Mixed effects statistical models were used to analyze these cognitive outcomes incorporating depression as a time-dependent covariate.
Participants with scores indicative of depression (PHQ-9 > 10) showed greater cognitive decline during 40-months follow-up on all tests, with the following differences in estimated least squares means: DSST 0.72 (95%CI 0.25, 1.19, p=0.0029), RAVLT 0.18 (95%CI 0.07, 0.29, p=0.0009), Stroop Interference −1.06 (95%CI −1.93, −0.18, p=0.0179). This effect of depression on risk of cognitive decline did not differ according to: previous cardiovascular disease, baseline cognition or age, intensive vs. standard treatment of glucose, blood pressure treatment, lipid treatment, or insulin use. Addition of demographic and clinical covariates to models did not significantly change the cognitive decline associated with depression.
Depression in patients with Type 2 diabetes was associated with greater cognitive decline in all domains, across all treatment arms, and in all participant subgroups assessed.
To quantify the effects of stabilizing the paralyzed trunk and pelvis with electrical stimulation on manual wheelchair propulsion.
Single-subject design case series with subjects acting as their own concurrent controls.
Hospital-based clinical biomechanics laboratory.
Six (4M, 2F age 46±10.8yrs) long-time users (6.1±3.9yrs) of implanted neuroprostheses for lower extremity function with chronic (8.6±2.8yrs) mid-cervical or thoracic level injuries (C6-T10).
Continuous low level stimulation to the hip (gluteus maximus, posterior adductor or hamstrings) and trunk extensor (lumbar erector spinae and/or quadratus lumborum) muscles with implanted intramuscular electrodes.
Main Outcome Measure(s)
Pushrim kinetics (peak resultant force, fraction effective force), kinematics (cadence, stroke length and maximum forward lean), and peak shoulder moment at preferred speed over 10m level surface; speed, pushrim kinetics and subjective ratings of effort for level 100m sprints and up a 30.5m ramp of approximately 5% grade.
Three out of five subjects demonstrated reduced peak resultant pushrim forces (p≤0.014) and improved efficiency, (p≤0.048) with stimulation during self-paced level propulsion. Peak sagittal shoulder moment remained unchanged in three subjects and increased in two others (p<0.001). Maximal forward trunk lean also increased by 19-26% (p<0.001) with stimulation in these three subjects. Stroke lengths were unchanged by stimulation in all subjects, and two showed extremely small (5%) but statistically significant increases in cadence (p≤0.021). Performance measures for sprints and inclines were generally unchanged with stimulation, however subjects consistently rated propulsion with stimulation to be easier for both surfaces.
Stabilizing the pelvis and trunk with low levels of continuous electrical stimulation to the lumbar trunk and hip extensors can positively impact the mechanics of manual wheelchair propulsion and reduce both perceived and physical measures of effort.
Neural Prostheses; Spinal Cord Injuries; Posture; Electrical Stimulation; Torso
Increased advanced glycation end products (AGEs) and oxidation products (OPs) are proposed to lead to progression of diabetic nephropathy (DN). We investigated the relationship between AGEs, OPs, and progression of DN in 103 subjects with type 1 diabetes participating in the Natural History of Diabetic Nephropathy Study.
RESEARCH DESIGN AND METHODS
Mean age of subjects was 17.6 ± 7.4 years, and mean duration of diabetes was 8.3 ± 4.9 years. All patients were normoalbuminuric. Change in glomerular basement membrane (GBM) width from baseline to 5 years, measured using electron micrographs of renal biopsies, was our primary end point, and mesangial fractional volume was a secondary end point. Fast progressors (FPs) were defined as those in the upper quartile of GBM change, and the remaining patients were classified as slow progressors (SPs). AGEs (3-deoxyglucosone and methylglyoxal hydroimidazolones [MGHI]), carboxymethyl lysine (CML), carboxyethyl lysine (CEL), and OPs (methionine sulfoxide and 2-aminoadipic acid) were measured at year 5 by liquid chromatography/triple-quadruple mass spectroscopy on 10-K plasma filtrates.
We found that MGHI, CEL, and CML levels were significantly higher in FPs relative to SPs. No product predicted mesangial expansion. A model containing only HbA1c accounted for 4.7% of GBM width variation, with the total variability explained by the model increasing to 11.6% when MGHI, CEL, and CML were added to the regression model (7.9% increase). MGHI was a significant independent predictor of FP. Using a logistic regression model to relate each biomarker to the probability of a subject’s classification as an FP, CML, CEL, and MGHI, but not HbA1c, showed a significant relationship to the probability of FP.
The results suggest that these three major AGEs may be early indicators of progression of important DN lesions.
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.
biomechanics; isometric joint moment; reaching; aging
To examine the relationship of cognitive performance to exposure to insulin (INS) and thiazolidinediones (TZD) in the ACCORD-MIND cohort.
Participants (55-80 yrs) with type 2 diabetes (T2D), hemoglobin A1c (HbA1c) >7.5% (>58 mmol/mol), and a high risk of cardiovascular events were randomly assigned to receive intensive control targeting HbA1c to < 6.0% (42 mmol/mol) or a standard strategy targeting HbA1c to 7.0-7.9% (53-63 mmol/mol). The Digit Symbol Substitution Test (DSST) was assessed at baseline and at 20 and 40 mo. Exposure to INS was calculated as average daily dose/kg of body weight; exposure to rosiglitazone (ROS) was calculated as days of ROS prescription in the intervals preceding the 20 and 40-mo DSSTs.
At baseline, INS use was associated with reduced DSST performance, but not after controlling for co-morbidities and lab values. There was no relationship between use of a TZD and DSST performance on at baseline. ROS but not INS exposure was associated with greater decline in DSST performance over 40 mo in subjects randomized to the intensive but not the standard group.
Exposure to a TZD may increase cognitive decline in some patients with T2D. However, these results may be confounded by unexplained differences between participants.
thiazolidinediones; insulin; diabetes; cognition
To determine the stimulated strength of the paralyzed gluteal and paraspinal muscles and their effects on the seated function of individuals with paralysis.
Case series with subjects acting as their own concurrent controls.
Hospital-based clinical biomechanics laboratory.
Eight users of implanted neuroprostheses for lower extremity function with low-cervical or thoracic level injuries.
Dynamometry and digital motion capture both with and without stimulation to the hip and trunk muscles.
Main Outcome Measure(s)
Isometric trunk extension moment at 0, 15 and 30 degrees of flexion; seated stability in terms of simulated isokinetic rowing; pelvic tilt, shoulder height, loaded and unloaded bimanual reaching to different heights, and subjective ratings of difficulty during unsupported sitting.
Stimulation produced significant increases in mean trunk extension moment (9.2±9.5Nm, p=0.0001) and rowing force (27.4±23.1N, p=0.0123) over baseline volitional values. Similarly, stimulation induced positive changes in average pelvic tilt (16.7±15.7deg) and shoulder height (2.2±2.5cm) during quiet sitting and bimanual reaching, and increased mean reach distance (5.5±6.6cm) over all subjects, target heights and loading conditions. Subjects consistently rated tasks with stimulation easier than voluntary effort alone.
In spite of considerable inter-subject variability, stabilizing the paralyzed trunk with electrical stimulation can positively impact seated posture, extend forward reach and allow exertion of larger forces on objects in the environment.
Neural Prostheses; Spinal Cord Injuries; Posture; Electrical Stimulation; Torso
To investigate the longitudinal performance of a surgically implanted neuroprosthesis for lower extremity exercise, standing, and transfers after spinal cord injury.
Research or outpatient physical therapy departments of four academic hospitals.
15 subjects with thoracic or low-cervical level spinal cord injuries who had received the 8-channel neuroprosthesis for exercise and standing.
After completing rehabilitation with the device, the subjects were discharged to unrestricted home use of the system. A series of assessments were performed before discharge and at a follow-up appointment approximately one year later.
Main Outcome Measure(s)
Neuroprosthesis usage, maximum standing time, body weight support, knee strength, knee fatigue index, electrode stability, and component survivability.
Levels of maximum standing time, body weight support, knee strength, and knee fatigue index were not statistically different from discharge to follow-up (p > 0.05). Additionally, neuroprosthesis usage was consistent with subjects choosing to use the system on approximately half of the days during each monitoring period. Although the number of hours using the neuroprosthesis remained constant, subjects shifted their usage to more functional standing versus more maintenance exercise, suggesting that the subjects incorporated the neuroprosthesis into their lives. Safety and reliability of the system were demonstrated by electrode stability and a high component survivability rate (>90%).
This group of 15 subjects is the largest cohort of implanted lower extremity neurorprosthetic exercise and standing system users. The safety and efficiency data from this group, and acceptance of the neuroprosthesis as demonstrated by continued usage, indicate that future efforts towards commercialization of a similar device may be warranted.
Electrical Stimulation; Exercise; Neural Prostheses; Spinal Cord Injuries; Weight-Bearing
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.
Obesity; Resistance training; Muscle strength; Muscle power; Voluntary weight loss.
Older adults face a number of barriers to receiving psychotherapy, such as a lack of transportation and access to providers. One way to overcome such barriers is to provide treatment by telephone. The purpose of this study was to examine the effects of cognitive behavioral therapy delivered by telephone (CBT-T) to older adults diagnosed with an anxiety disorder.
Randomized controlled trial.
Sixty participants ≥ 60 years of age with a diagnosis of Generalized Anxiety Disorder, Panic Disorder, or Anxiety Disorder Not Otherwise Specified.
CBT-T vs. information-only comparison.
Co-primary outcomes included worry (Penn State Worry Questionnaire) and general anxiety (State Trait Anxiety Inventory). Secondary outcomes included clinician-rated anxiety (Hamilton Anxiety Rating Scale), anxiety sensitivity (Anxiety Sensitivity Index), depressive symptoms (Beck Depression Inventory), quality of life (SF-36), and sleep (Insomnia Severity Index). Assessments were completed prior to randomization, immediately upon completion of treatment, and 6 months after completing treatment.
CBT-T was superior to information-only in reducing general anxiety (ES = 0.71), worry (ES = 0.61), anxiety sensitivity (ES = 0.85), and insomnia (ES = 0.82) at the post-treatment assessment; however, only the reductions in worry were maintained by the 6 month follow-up assessment (ES = 0.80).
These results suggest that CBT-T may be efficacious in reducing anxiety and worry in older adults, but additional sessions may be needed to maintain these effects.
anxiety; cognitive-behavioral therapy; elderly; Generalized Anxiety Disorder; Panic Disorder; telephone-delivered psychotherapy
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.
resistance exercise; falls; muscle strength; muscle power; exercise intervention; randomized trial
Generalized Anxiety Disorder (GAD), characterized by excessive and uncontrollable worry, has a negative impact on the health, well-being, and functioning of older adults. Cognitive behavioral therapy has demonstrated efficacy in reducing anxiety and worry in older adults, but the generalizability of these findings to community-dwelling older adults is unknown. The aim of the current study is to examine the efficacy of a cognitive-behavioral intervention delivered by telephone in reducing anxiety and worry in rural community-dwelling older adults with GAD.
We propose a randomized controlled trial comparing telephone-delivered cognitive behavioral therapy (CBT-T) with nondirective supportive therapy (NST-T). One hundred seventy six adults 60 years and older diagnosed with GAD will be randomized to one of the two treatment conditions. The primary outcomes are self-report worry and clinician-rated anxiety. Secondary outcomes include depressive symptoms, sleep, quality of life, and functional status.
It is hypothesized that CBT-T will be superior to NST-T in reducing anxiety and worry among older adults with GAD. Further, CBT-T is hypothesized to be superior to NST-T in reducing problems with depressive symptoms, sleep, functional status and quality of life. If this program is successful, it could be implemented as a low-cost program to treat late-life anxiety, especially in rural areas or in circumstances where older adults may not have access to qualified mental health providers.
clinicaltrials.gov Identifier: NCT01259596
Generalized anxiety disorder; Older adults; Randomized controlled trial; Rural mental health; Telephone-delivered psychotherapy
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.
resistance exercise; exercise prescription; relative intensity; reliability; older adults; blood pressure
Clinical recommendation of weight loss (WL) in older adults remains controversial, partially due to concerns regarding lean mass loss and potential loss of physical function. The purpose of this study is to determine the independent associations between changes in fat and lean mass and changes in physical function in older, overweight, and obese adults undergoing intentional WL.
Data from three randomized-controlled trials of intentional WL in older adults with similar functional outcomes (short physical performance battery and Pepper assessment tool for disability) were combined. Analyses of covariance models were used to investigate relationships between changes in weight, fat, and lean mass (acquired using dual-energy x-ray absorptiometry) and changes in physical function.
Overall loss of body weight was −7.8 ± 6.1 kg (−5.6 ± 4.1 kg and −2.7 ± 2.4 kg of fat and lean mass, respectively). In all studies combined, after adjustment for age, sex, and height, overall WL was associated with significant improvements in self-reported mobility disability (p < .01) and walking speed (p < .01). Models including change in both fat and lean mass as independent variables found only the change in fat mass to significantly predict change in mobility disability (β[fat] = 0.04; p < .01) and walking speed (β[fat] = −0.01; p < .01).
Results from this study demonstrate that loss of body weight, following intentional WL, is associated with significant improvement in self-reported mobility disability and walking speed in overweight and obese older adults. Importantly, fat mass loss was found to be a more significant predictor of change in physical function than lean mass loss.
Physical function; Weight loss; Fat mass; Lean mass; Aging
The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase III randomized controlled clinical trial (Clinicaltrials.gov 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.
aging; accelerometry; physical disability; compromised physical function; older adults
The transport of DNA into eukaryotic cells is minimal because of the cell membrane barrier, and this limits the application of DNA vaccines, gene silencing, and gene therapy. Several available transfection reagents and techniques have been used to circumvent this problem. Alternatively, nonviral nanoscale vectors have been shown to bypass the eukaryotic cell membrane. In the present work, we developed a unique nanomaterial, pHEMA+chitosan nanospheres (PCNSs), which consisted of poly(2-hydroxyethyl methacrylate) nanospheres surrounded by a chitosan cationic shell, and we used this for encapsulation of a respiratory syncytial virus (RSV)-F gene construct (a model for a DNA vaccine). The new nanomaterial was capable of transfecting various eukaryotic cell lines without the use of a commercial transfection reagent. Using transmission electron microscopy, (TEM), fluorescence activated cell sorting (FACS), and immunofluorescence, we clearly demonstrated that the positively charged PCNSs were able to bind to the negatively charged cell membrane and were taken up by endocytosis, in Cos-7 cells. Using quantitative polymerase chain reaction (qPCR), we also evaluated the efficiency of transfection achieved with PCNSs and without the use of a liposomal-based transfection mediator, in Cos-7, HEp-2, and Vero cells. To assess the transfection efficiency of the PCNSs in vivo, these novel nanomaterials containing RSV-F gene were injected intramuscularly into BALB/c mice, resulting in high copy number of the transgene. In this study, we report, for the first time, the application of the PCNSs as a nanovehicle for gene delivery in vitro and in vivo.
pHEMA+chitosan nanoparticles; nonviral vector; RSV-DNA vaccine
Self-management of type 2 diabetes including avoidance of hypoglycemia is complex, but the impact of cognition on safe self-management is not well understood. This study aimed to assess the effect of baseline cognitive function and cognitive decline on subsequent risk of severe hypoglycemia and to assess the effect of different glycemic strategies on these relationships.
RESEARCH DESIGN AND METHODS
Prospective cohort analysis of data from the ACCORD trial included 2,956 adults aged ≥55 years with type 2 diabetes and additional cardiovascular risk factors. Cognitive tests (Digit Symbol Substitution Test [DSST], Rey Auditory Verbal Learning Test, Stroop Test, and Mini Mental Status Examination) were conducted at baseline and 20 months. Study outcomes were incident confirmed severe hypoglycemia requiring medical assistance (HMA) and hypoglycemia requiring any assistance (HAA).
After a median 3.25-year follow-up, a 5-point-poorer baseline score on the DSST was predictive of a first episode of HMA (hazard ratio 1.13 [95% CI 1.08–1.18]). Analyses of the other cognitive tests and of HAA were consistent with the DSST results. Cognitive decline over 20 months increased the risk of subsequent hypoglycemia to a greater extent in those with lower baseline cognitive function (Pinteraction = 0.037). Randomization to an intensive versus standard glycemic strategy had no impact on the relationship between cognitive function and the risk of severe hypoglycemia.
Poor cognitive function increases the risk of severe hypoglycemia in patients with type 2 diabetes. Clinicians should consider cognitive function in assessing and guiding their patients regarding safe diabetes self-management regardless of their glycemic targets.
The aim of this study was to examine the relationship between frequent and unrecognized hypoglycemia and mortality in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study cohort.
RESEARCH DESIGN AND METHODS
A total of 10,096 ACCORD study participants with follow-up for both hypoglycemia and mortality were included. Hazard ratios (95% CIs) relating the risk of death to the updated annualized number of hypoglycemic episodes and the updated annualized number of intervals with unrecognized hypoglycemia were obtained using Cox proportional hazards regression models, allowing for these hypoglycemia variables as time-dependent covariates and controlling for the baseline covariates.
Participants in the intensive group reported a mean of 1.06 hypoglycemic episodes (self-monitored blood glucose <70 mg/dL or <3.9 mmol/L) in the 7 days preceding their regular 4-month visit, whereas participants in the standard group reported an average of 0.29 episodes. Unrecognized hypoglycemia was reported, on average, at 5.8% of the intensive group 4-month visits and 2.6% of the standard group visits. Hazard ratios for mortality in models including frequency of hypoglycemic episodes were 0.93 (95% CI 0.9–0.97; P < 0.001) for participants in the intensive group and 0.98 (0.91–1.06; P = 0.615) for participants in the standard group. The hazard ratios for mortality in models, including unrecognized hypoglycemia, were not statistically significant for either group.
Recognized and unrecognized hypoglycemia was more common in the intensive group than in the standard group. In the intensive group of the ACCORD study, a small but statistically significant inverse relationship of uncertain clinical importance was identified between the number of hypoglycemic episodes and the risk of death among participants.
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.
Muscle volume; Strength; Upper limb; Aging; Joint moment
The purposes of this study are to determine the frequency and severity of insomnia symptoms and related complaints experienced by older adults with GAD and compare them with older adults without GAD; compare insomnia symptoms among older adults with GAD with and without comorbid depression; determine if there are age differences in insomnia severity among people with GAD; and determine if there are differences in insomnia severity between older adults with GAD and older adults diagnosed with insomnia.
Participants were recruited through primary care clinics, advertisements, and mass mailings.
110 older adults; 31 with GAD, 25 with GAD and depression, 33 worried well, and 21 with no psychiatric diagnosis.
Psychiatric diagnosis, sleep disturbance, and health.
Participants with GAD with and without comorbid depression reported significantly greater sleep disturbance severity than participants with no psychiatric diagnosis and the worried well. There were no differences in sleep disturbances between older adults with GAD only and older adults with comorbid GAD and depression. The severity of sleep disturbance reported by older participants with GAD was greater than reports by young and middle-aged participants with GAD, and comparable to reports by older adults with a diagnosis of insomnia.
Ninety percent of older adults with GAD report dissatisfaction with sleep and the majority report moderate to severe insomnia. These findings support the assessment of sleep disturbances within the context of late-life GAD.
Anxiety; GAD; insomnia; sleep
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.
Physical disability; Physical activity; Older adults
Persons with type 2 diabetes (T2D) are at risk for cognitive impairment and brain atrophy. The ACCORD Memory in Diabetes (MIND) Study investigated whether persons randomized to an intensive glycaemic therapeutic strategy targeting HbA1c to <6% had better cognitive function and a larger brain volume at 40 months than persons randomized to a standard strategy targeting HbA1c to 7%–7.9%.
ACCORD MIND was a double 2×2 factorial parallel group randomised trial conducted in 52 clinical sites in North America. Participants [age 55 – <80 years] with T2D, high HbA1c concentrations (>7.5%), and at high risk for cardiovascular events were randomised to treatment groups using a centralized web-based system. Clinic staff and participants were not blinded to treatment arm. The cognitive primary outcome, the Digit Symbol Substitution Test (DSST) score, was assessed at baseline, 20 and 40 months. Total brain volume (TBV), the primary brain structure outcome, was assessed with MRI at baseline and 40 months in a sub-set of 632 participants. All participants with follow-up data were included in the primary analyses. In February, 2008, increased mortality risk led to the termination of the intensive therapy and transition of those participants to standard glycaemic treatment.
Randomised patients (n=2977; mean age 62.3 years) were consecutively enrolled; the final analysis included 1358 intensive and 1416 standard arm participants with a 20 or 40 month DSST score. Of the 614 with a baseline MRI, 230 intensive and 273 standard therapy participants were included in the analysis. There was no treatment difference in the DSST score. The intensive group had a greater TBV than the standard group (difference, 4.62; 95% CI 2.0 to7.3 cm3; p=0.0007).
Although significant differences in TBV favored the intensive therapy, cognitive outcomes were not different. Combined with the unfavorable effects on other ACCORD outcomes, MIND findings do not support using intensive therapy to reduce the adverse effects of diabetes on the brain in patients similar to MIND participants. (ClinicalTrials.gov number, NCT00182910).
Despite the prevalence and impact of Generalized Anxiety Disorder (GAD) in the primary care setting, little is known about its presentation in this setting. The purpose of this study is to examine age and racial differences in the presentation and treatment of GAD in medical patients. Participants were recruited from one family medicine clinic and one internal medicine clinic. The prevalence of GAD was lowest for older adults. Age differences were found in the presentation of GAD, with young adults reporting greater cognitive symptoms of anxiety, negative affect, and depressive symptoms. African-Americans with GAD reported more positive affect and lower rates of treatment. The lower levels of negative affect and depressive symptoms reported among older adults may affect the recognition of GAD by primary care physicians. Further research is needed to better understand the causes of racial differences in treatment.
age differences; anxiety; elderly; Generalized Anxiety Disorder; racial differences