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2.  An Evidence-Based Comparison of Operational Criteria for the Presence of Sarcopenia 
Several consensus groups have previously published operational criteria for sarcopenia, incorporating lean mass with strength and/or physical performance. The purpose of this manuscript is to describe the prevalence, agreement, and discrepancies between the Foundation for the National Institutes of Health (FNIH) criteria with other operational definitions for sarcopenia.
The FNIH Sarcopenia Project used data from nine studies including: Age, Gene and Environment Susceptibility-Reykjavik Study; Boston Puerto Rican Health Study; a series of six clinical trials from the University of Connecticut; Framingham Heart Study; Health, Aging, and Body Composition Study; Invecchiare in Chianti; Osteoporotic Fractures in Men Study; Rancho Bernardo Study; and Study of Osteoporotic Fractures. Participants included in these analyses were aged 65 and older and had measures of body mass index, appendicular lean mass, grip strength, and gait speed.
The prevalence of sarcopenia and agreement proportions was higher in women than men. The lowest prevalence was observed with the FNIH criteria (1.3% men and 2.3% women) compared with the International Working Group and the European Working Group for Sarcopenia in Older Persons (5.1% and 5.3% in men and 11.8% and 13.3% in women, respectively). The positive percent agreements between the FNIH criteria and other criteria were low, ranging from 7% to 32% in men and 5% to 19% in women. However, the negative percent agreement were high (all >95%).
The FNIH criteria result in a more conservative operational definition of sarcopenia, and the prevalence was lower compared with other proposed criteria. Agreement for diagnosing sarcopenia was low, but agreement for ruling out sarcopenia was very high. Consensus on the operational criteria for the diagnosis of sarcopenia is much needed to characterize populations for study and to identify adults for treatment.
PMCID: PMC3991139  PMID: 24737561
Muscle; Sarcopenia; Lean mass.
3.  Criteria for Clinically Relevant Weakness and Low Lean Mass and Their Longitudinal Association With Incident Mobility Impairment and Mortality: The Foundation for the National Institutes of Health (FNIH) Sarcopenia Project 
This analysis sought to determine the associations of the Foundation for the National Institutes of Health Sarcopenia Project criteria for weakness and low lean mass with likelihood for mobility impairment (gait speed ≤ 0.8 m/s) and mortality. Providing validity for these criteria is essential for research and clinical evaluation.
Among 4,411 men and 1,869 women pooled from 6 cohort studies, 3-year likelihood for incident mobility impairment and mortality over 10 years were determined for individuals with weakness, low lean mass, and for those having both. Weakness was defined as low grip strength (<26kg men and <16kg women) and low grip strength-to-body mass index (BMI; kg/m2) ratio (<1.00 men and <0.56 women). Low lean mass (dual-energy x-ray absorptiometry) was categorized as low appendicular lean mass (ALM; <19.75kg men and <15.02kg women) and low ALM-to-BMI ratio (<0.789 men and <0.512 women).
Low grip strength (men: odds ratio [OR] = 2.31, 95% confidence interval [CI] = 1.34–3.99; women: OR = 1.99, 95% CI 1.23–3.21), low grip strength-to-BMI ratio (men: OR = 3.28, 95% CI 1.92–5.59; women: OR = 2.54, 95% CI 1.10–5.83) and low ALM-to-BMI ratio (men: OR = 1.58, 95% CI 1.12–2.25; women: OR = 1.81, 95% CI 1.14–2.87), but not low ALM, were associated with increased likelihood for incident mobility impairment. Weakness increased likelihood of mobility impairment regardless of low lean mass. Mortality risk patterns were inconsistent.
These findings support our cut-points for low grip strength and low ALM-to-BMI ratio as candidate criteria for clinically relevant weakness and low lean mass. Further validation in other populations and for alternate relevant outcomes is needed.
PMCID: PMC3991140  PMID: 24737560
Muscle; Sarcopenia; Mobility; Impairment.
4.  Cutpoints for Low Appendicular Lean Mass That Identify Older Adults With Clinically Significant Weakness 
Low lean mass is potentially clinically important in older persons, but criteria have not been empirically validated. As part of the FNIH (Foundation for the National Institutes of Health) Sarcopenia Project, this analysis sought to identify cutpoints in lean mass by dual-energy x-ray absorptiometry that discriminate the presence or absence of weakness (defined in a previous report in the series as grip strength <26kg in men and <16kg in women).
In pooled cross-sectional data stratified by sex (7,582 men and 3,688 women), classification and regression tree (CART) analysis was used to derive cutpoints for appendicular lean body mass (ALM) that best discriminated the presence or absence of weakness. Mixed-effects logistic regression was used to quantify the strength of the association between lean mass category and weakness.
In primary analyses, CART models identified cutpoints for low lean mass (ALM <19.75kg in men and <15.02kg in women). Sensitivity analyses using ALM divided by body mass index (BMI: ALMBMI) identified a secondary definition (ALMBMI <0.789 in men and ALMBMI <0.512 in women). As expected, after accounting for study and age, low lean mass (compared with higher lean mass) was associated with weakness by both the primary (men, odds ratio [OR]: 6.9 [95% CI: 5.4, 8.9]; women, OR: 3.6 [95% CI: 2.9, 4.3]) and secondary definitions (men, OR: 4.3 [95% CI: 3.4, 5.5]; women, OR: 2.2 [95% CI: 1.8, 2.8]).
ALM cutpoints derived from a large, diverse sample of older adults identified lean mass thresholds below which older adults had a higher likelihood of weakness.
PMCID: PMC3991141  PMID: 24737559
Muscle; Sarcopenia; Cutpoints.
5.  The FNIH Sarcopenia Project: Rationale, Study Description, Conference Recommendations, and Final Estimates 
Low muscle mass and weakness are common and potentially disabling in older adults, but in order to become recognized as a clinical condition, criteria for diagnosis should be based on clinically relevant thresholds and independently validated. The Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project used an evidence-based approach to develop these criteria. Initial findings were presented at a conference in May 2012, which generated recommendations that guided additional analyses to determine final recommended criteria. Details of the Project and its findings are presented in four accompanying manuscripts.
The Foundation for the National Institutes of Health Sarcopenia Project used data from nine sources of community-dwelling older persons: Age, Gene/Environment Susceptibility-Reykjavik Study, Boston Puerto Rican Health Study, a series of six clinical trials, Framingham Heart Study, Health, Aging, and Body Composition, Invecchiare in Chianti, Osteoporotic Fractures in Men Study, Rancho Bernardo Study, and Study of Osteoporotic Fractures. Feedback from conference attendees was obtained via surveys and breakout groups.
The pooled sample included 26,625 participants (57% women, mean age in men 75.2 [±6.1 SD] and in women 78.6 [±5.9] years). Conference attendees emphasized the importance of evaluating the influence of body mass on cutpoints. Based on the analyses presented in this series, the final recommended cutpoints for weakness are grip strength <26kg for men and <16kg for women, and for low lean mass, appendicular lean mass adjusted for body mass index <0.789 for men and <0.512 for women.
These evidence-based cutpoints, based on a large and diverse population, may help identify participants for clinical trials and should be evaluated among populations with high rates of functional limitations.
PMCID: PMC3991146  PMID: 24737557
Aging; Sarcopenia; Muscle; Outcomes; Weakness.
6.  Grip Strength Cutpoints for the Identification of Clinically Relevant Weakness 
Weakness is common and contributes to disability, but no consensus exists regarding a strength cutpoint to identify persons at high risk. This analysis, conducted as part of the Foundation for the National Institutes of Health Sarcopenia Project, sought to identify cutpoints that distinguish weakness associated with mobility impairment, defined as gait speed less than 0.8 m/s.
In pooled cross-sectional data (9,897 men and 10,950 women), Classification and Regression Tree analysis was used to derive cutpoints for grip strength associated with mobility impairment.
In men, a grip strength of 26–32 kg was classified as “intermediate” and less than 26 kg as “weak”; 11% of men were intermediate and 5% were weak. Compared with men with normal strength, odds ratios for mobility impairment were 3.63 (95% CI: 3.01–4.38) and 7.62 (95% CI 6.13–9.49), respectively. In women, a grip strength of 16–20 kg was classified as “intermediate” and less than 16 kg as “weak”; 25% of women were intermediate and 18% were weak. Compared with women with normal strength, odds ratios for mobility impairment were 2.44 (95% CI 2.20–2.71) and 4.42 (95% CI 3.94–4.97), respectively. Weakness based on these cutpoints was associated with mobility impairment across subgroups based on age, body mass index, height, and disease status. Notably, in women, grip strength divided by body mass index provided better fit relative to grip strength alone, but fit was not sufficiently improved to merit different measures by gender and use of a more complex measure.
Cutpoints for weakness derived from this large, diverse sample of older adults may be useful to identify populations who may benefit from interventions to improve muscle strength and function.
PMCID: PMC3991145  PMID: 24737558
Muscle; Sarcopenia; Grip strength; Physical function; Gait speed.
7.  White Matter Hyperintensities, Exercise and Improvement in Gait Speed: Does the Type of Gait Rehabilitation Matter? 
Journal of the American Geriatrics Society  2013;61(5):10.1111/jgs.12211.
Background and Objectives
White matter hyperintensities (WMH) on brain MRI are associated with cognitive and mobility impairment in older adults. We examined whether WMH in tracts in older adults with mobility impairment are linked to outcomes of gait rehabilitation interventions.
A 12-week randomized controlled single-blind trial.
University-based mobility research laboratory.
Ambulatory adults aged 65 and older with mobility impairment.
A conventional gait intervention focusing on walking, endurance, balance, and strength (WEBS, n=21) compared to a task-oriented intervention focused on timing and coordination of gait (TC, n=23).
We measured self-paced gait speed over an instrumented walkway, pre and post intervention, and quantified WMH and brain volumes on pre-intervention brain MRI using an automated segmentation process. We overlaid a white matter tract atlas on the segmented images to measure tract WMH volumes and normalized WMH volumes to total brain volume. Aggregate WMH volumes in all white matter tracts and individual WMH volumes in specific longitudinal tracts (the superior longitudinal fasciculus, inferior longitudinal fasciculus and the fronto-occipital fasciculus) and cingulum were obtained.
Gait speed gains in the TC group were of the same magnitude, independent of the WMH volume measures in all except the cingulum. However, in the WEBS group, gain in gait speed was smaller with greater overall tract WMH volumes (P<0.001) and with greater WMH volume in the three longitudinal tracts (P< 0.001 to 0.025).
Gains in gait speed with two types of gait rehabilitation are associated with individual differences in WMH. Task-oriented therapy that targets timing and coordination of gait may particularly benefit older adults with WMH in brain tracts that influence gait and cognition.
PMCID: PMC3874589  PMID: 23590257
8.  Early Hospital Readmission is a Predictor of One-Year Mortality in Community-Dwelling Older Medicare Beneficiaries 
Journal of General Internal Medicine  2012;27(11):1467-1474.
Hospital readmission within thirty days is common among Medicare beneficiaries, but the relationship between rehospitalization and subsequent mortality in older adults is not known.
To compare one-year mortality rates among community-dwelling elderly hospitalized Medicare beneficiaries who did and did not experience early hospital readmission (within 30 days), and to estimate the odds of one-year mortality associated with early hospital readmission and with other patient characteristics.
A cohort study of 2133 hospitalized community-dwelling Medicare beneficiaries older than 64 years, who participated in the nationally representative Cost and Use Medicare Current Beneficiary Survey between 2001 and 2004, with follow-up through 2006.
One-year mortality after index hospitalization discharge.
Three hundred and four (13.7 %) hospitalized beneficiaries had an early hospital readmission. Those with early readmission had higher one-year mortality (38.7 %) than patients who were not readmitted (12.1 %; p < 0.001). Early readmission remained independently associated with mortality after adjustment for sociodemographic factors, health and functional status, medical comorbidity, and index hospitalization-related characteristics [HR (95 % CI) 2.97 (2.24-3.92)]. Other patient characteristics independently associated with mortality included age [1.03 (1.02-1.05) per year], low income [1.39 (1.04-1.86)], limited self-rated health [1.60 (1.20-2.14)], two or more recent hospitalizations [1.47 (1.01-2.15)], mobility difficulty [1.51 (1.03-2.20)], being underweight [1.62 (1.14-2.31)], and several comorbid conditions, including chronic lung disease, cancer, renal failure, and weight loss. Hospitalization-related factors independently associated with mortality included longer length of stay, discharge to a skilled nursing facility for post-acute care, and primary diagnoses of infections, cancer, acute myocardial infarction, and heart failure.
Among community-dwelling older adults, early hospital readmission is a marker for notably increased risk of one-year mortality. Providers, patients, and families all might respond profitably to an early readmission by reviewing treatment plans and goals of care.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-012-2116-3) contains supplementary material, which is available to authorized users.
PMCID: PMC3475824  PMID: 22692634
readmission; mortality; older adults; care transitions
9.  Use of Stance Time Variability for Predicting Mobility Disability in Community-Dwelling Older Persons: A Prospective Study 
Background and Purpose
Mobility disability is a serious and frequent adverse health outcome associated with aging. Early identification of individuals at risk for mobility disability is important if interventions to prevent disability are to be instituted. The objectives of this prospective study were to: 1) determine the magnitude of stance time variability (STV) that discriminates individuals who currently have mobility disability (prevalent mobility disability) and 2) determine the magnitude of STV that predicts a new onset of mobility disability at one year (incident mobility disability).
552 community-dwelling older adults were evaluated as part of the Cardiovascular Health Study, a longitudinal cohort study. Stance time, in milliseconds (ms), was determined from 2 passes on a 4-meter computerized walkway at self-selected walking speed, and STV was defined as the standard deviation (SD) from approximately 12 individual steps. Mobility disability was defined as self-reported difficulty walking a half mile. Receiver operating characteristic (ROC) curves were plotted to determine an optimal cutoff value for stance time variability for prevalent and incident mobility disability, and the area under the ROC curve was computed.
The optimal cut-off score for STV (maximizing sensitivity and specificity) for prevalent mobility disability was 0.037 sec(sensitivity = 65%, specificity = 65%, AUC = 0.70) and for incident 1 year mobility disability was 0.034 sec(sensitivity = 61%, specificity = 60%, AUC = 0.65). The use of likelihood ratios demonstrated a gradient of risk across values of STV, with mobility risk increasing as values of STV increased.
Discussion and Conclusion
Values of STV may be useful in identifying older adults with mobility disability and at risk for future disability. We recommend the more conservative estimate for identifying risk, STV=0.034 s, which maximizes the sensitivity and minimizes false negatives. The relatively modest values on the validity indices could possibly be improved by increasing the reliability of the measurement of STV. Clinicians should interpret the cut-off values liberally and use STV in conjunction with other measures until further work is completed to validate STV as an indicator of mobility disability.
PMCID: PMC3349774  PMID: 22314273
Gait variability; Disability; Sensitivity; Specificity; Older Adults
10.  The Relationship of Vitamin B12 and Sensory and Motor Peripheral Nerve Function in Older Adults 
To examine whether deficient B12 status or low serum B12 levels are associated with worse sensory and motor peripheral nerve function in older adults.
Health, Aging and Body Composition Study.
Two thousand two hundred eighty-seven adults aged 72–83 years [mean age: 76.5 ± 2.9 years; 51.4% female; 38.3% black].
Low serum B12 was defined based solely on serum B12 of <260 pmol/L, whereas deficient B12 status was defined as B12 <260 pmol/L, methylmalonic acid [MMA] >271 nmol/L and MMA >2-methylcitrate. Peripheral nerve function was assessed by peroneal nerve conduction amplitude and velocity [NCV] (motor); 1.4g/10g monofilament detection; average vibration threshold detection; and peripheral neuropathy symptoms [numbness; aching/burning pain] (sensory).
B12 deficient status was found in 7.0% and an additional 10.1% had low serum B12 levels. B12 deficient status was associated with greater insensitivity to light (1.4g) touch (OR: 1.50; 95% CI: [1.06, 2.13]) and worse NCV [42.3 m/s vs. 43.5 m/s] (β =−1.16; p=0.01), after multivariable adjustment for demographics, lifestyle factors, and health conditions. Associations were consistent for the alternative definition using low serum B12 only. No significant associations were found for deficient B12 status or the alternative low serum B12 definition and vibration detection, nerve conduction amplitude, or peripheral neuropathy symptoms.
Poor B12 (deficient B12 status and low serum B12) is associated with worse sensory and motor peripheral nerve function. Nerve function impairments may lead to physical function declines and disability in older adults, suggesting that prevention and treatment of low B12 levels may be important to evaluate.
PMCID: PMC3376015  PMID: 22690982
low B12; deficient B12; sensory peripheral nerve function; motor nerve conduction; older adults
11.  Vitamin B12 and Homocysteine Levels and 6-Year Change in Peripheral Nerve Function and Neurological Signs 
Low vitamin B12 and high homocysteine (Hcy) levels are common in older adults and may be associated with worse neurological function. The aim of this study is to determine whether changes in B12 or Hcy levels are associated with longitudinal changes in peripheral nerve function and clinical neurological signs and symptoms.
Participants aged 60 years and older at baseline (n = 678; 72.2 ± 6.2 years; 43.5% male) were from the InCHIANTI Study. Low B12 (<260 pmol/L) and high Hcy (≥13 μmol/L) were measured at baseline and 3-year follow-up. Neurological function was assessed by peroneal nerve conduction amplitude (compound motor action potential) and velocity, neurological examination, and peripheral neuropathy symptoms at baseline, 3-year, and 6-year follow-up.
At baseline, 43.8% had low B12 levels and 58.6% had high Hcy levels. Over 6 years, 12.4% declined to poor compound motor action potential (<1 mV) and 42.1% declined to poor nerve conduction velocity (<40 m/s). In mixed models analyses, sustained high Hcy was associated with worse compound motor action potential compared with sustained normal Hcy (p = .04), adjusting for demographics, diabetes, and folate level. Participants whose Hcy level became high at follow-up were more likely to become unable to detect monofilament at 6-year follow-up compared with those with sustained normal Hcy (odds ratio: 5.4; 95% CI: 1.5–19.0), adjusting for demographics, diabetes, body mass index, and peripheral arterial disease. There was no association with vitamin B12 level or with symptoms.
High Hcy may be associated with worse sensory and motor peripheral nerve function. Because poor nerve function has been associated with lower strength and physical performance, these results have important implications for disability in older adults.
PMCID: PMC3326240  PMID: 22156506
Vitamin B12; Homocysteine; Peripheral nerve function; Neurological signs
12.  Slower gait, slower information processing and smaller prefrontal area in older adults 
Age and Ageing  2011;41(1):58-64.
Background: slower gait in older adults is related to smaller volume of the prefrontal area (PFAv). The pathways underlying this association have not yet been explored. Understanding slowing gait could help improve function in older age. We examine whether the association between smaller PFAv and slower gait is explained by lower performance on numerous neuropsychological tests.
Hypothesis: we hypothesise that slower information processing explains this association, while tests of language or memory will not.
Methods: data on brain imaging, neuropsychological tests (information processing speed, visuospatial attention, memory, language, mood) and time to walk 15 feet were obtained in 214 adults (73.3 years, 62% women) free from stroke and dementia. Covariates included central (white matter hyperintensities, vision) and peripheral contributors of gait (vibration sense, muscle strength, arthritis, body mass index), demographics (age, race, gender, education), as well as markers of prevalent vascular diseases (cardiovascular disease, diabetes and ankle arm index).
Results: in linear regression models, smaller PFAv was associated with slower time to walk independent of covariates. This association was no longer significant after adding information processing speed to the model. None of the other neuropsychological tests significantly attenuated this association.
Conclusions: we conclude that smaller PFAv may contribute to slower gait through slower information processing. Future longitudinal studies are warranted to examine the casual relationship between focal brain atrophy with slowing in information processing and gait.
PMCID: PMC3234076  PMID: 21965414
prefrontal volume; gait speed; information processing; elderly
14.  Is Timed Up and Go Better Than Gait Speed in Predicting Health, Function, and Falls in Older Adults? 
While gait speed (GS) predicts many outcomes in older adults, Timed Up and Go (TUG) is recommended for clinical assessment of mobility and fall risk. The two measures are rarely compared. We assessed whether TUG is superior to GS in predicting multiple geriatric outcomes.
Prospective cohort study.
Medicare health maintenance organization and Veterans’ Affairs primary care clinics.
Adults aged 65 years and older (N = 457).
Baseline GS and TUG were used to predict health decline by EuroQol and SF-36 global health; functional decline by NHIS ADL score and SF-36 physical function index; hospitalization; and single and recurrent falls over 1 year.
Mean age was 74 years and 44% were female. Odds ratios for all outcomes were equivalent for GS and TUG. Using area under the ROC curve ≥ 0.7 for acceptable predictive ability, GS and TUG each alone predicted decline in global health, new ADL difficulty, and falls, with no difference in predictive ability between performance measures. Neither performance measure predicted hospitalization, EuroQol decline, or physical function decline. As continuous variables, TUG did not add predictive ability to GS for any outcome.
GS predicts most geriatric outcomes, including falls, as does the TUG. The time alone in TUG may not add to information provided by GS, although its qualitative elements may have other utility.
PMCID: PMC3522463  PMID: 21410448
gait speed; Timed Up and Go; physical performance; falls; hospitalization
15.  Analgesic Use for Knee and Hip Osteoarthritis in Community-Dwelling Elders 
Pain medicine (Malden, Mass.)  2011;12(11):1628-1636.
To examine the prevalence and correlates of non-opioid and opioid analgesic use and descriptively evaluate potential undertreatment in a sample of community-dwelling elders with symptomatic knee and/or hip osteoarthritis (OA).
Health, Aging and Body Composition Study
652 participants attending the year 6 visit (2002-03) with symptomatic knee and/or hip OA.
Outcome Measures
Analgesic use was defined as taking ≥ 1 non-opioid and/or ≥ 1 opioid receptor agonist. Non-opioid and opioid doses were standardized across all agents by dividing the daily dose used by the minimum effective analgesic daily dose. Inadequate pain control was defined as severe/extreme OA pain in the past 30 days from a modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).
Just over half (51.4%) reported taking at least one non-opioid analgesic and approximately 10% were taking an opioid, most (88.5%) of whom also took a non-opioid. One in five participants (19.3%) had inadequate pain control, 39% of whom were using < 1 standardized daily dose of either a non-opioid or opioid analgesic. In adjusted analyses, severe/extreme OA pain was significantly associated with both non-opioid (adjusted odds ratio [AOR]=2.44; 95% confidence interval [95% CI]=1.49-3.99) and opioid (AOR=2.64; 95% CI, 1.26-5.53) use.
Although older adults with severe/extreme knee and/or hip OA pain are more likely to take analgesics than those with less severe pain, a sizable proportion take less than therapeutic doses and thus may be undertreated. Further research is needed to examine barriers to optimal analgesic use.
PMCID: PMC3221937  PMID: 21992521
Aged; Analgesic; Osteoarthritis
16.  Age-Related Striatal Dopaminergic Denervation and Severity of a Slip Perturbation 
Striatal dopamine activity declines with normal aging. Age-related striatal dopaminergic denervation (SDD) has been implicated in standing balance and unperturbed gait. The goal of this study was to analyze the association between the degree of SDD and the magnitude of an unexpected slip perturbation induced during gait.
Fifty healthy participants aged 20–86 years old underwent dopamine transporter positron emission tomography to classify SDD severity as mild, moderate, or severe. Participants also walked on a floor that was unexpectedly contaminated with a glycerol solution for gait testing. The magnitude of a slip was quantified using the peak slip velocity (PSV), measured at the slipping foot. Data were analyzed for both fast (greater than 1.2 m/s) and slow walkers as gait speed correlated with slip severity. All data analyses were age adjusted.
Greater severity of dopaminergic denervation in the caudate nucleus was correlated with higher PSV (p < .01) but only in the fast speed walking group. The relationship between SDD in the putamen and slip severity was not statistically significant in fast and slow walkers.
Age-related SDD may impact the ability to recover from large perturbations during walking in individuals who typically walk fast. This effect, prominent in the caudate nucleus, may implicate a role of cognitive frontostriatal pathways in the executive control of gait when balance is challenged by large perturbations. Finally, a cautious gait behavior present in slow walkers may explain the apparent lack of involvement of striatal dopaminergic pathways in postural responses to slips.
PMCID: PMC3202904  PMID: 21746736
Falls; Slips; Striatal dopamine
17.  Use of Motor Abundance in Young and Older Adults during Dual-Task Treadmill Walking 
PLoS ONE  2012;7(7):e41306.
Motor abundance allows individuals to perform any task reliably while being variable in movement's particulars. The study investigated age-related differences in this feature when young adults (YA) and older adults (OA) performed challenging tasks, namely treadmill walking alone and while performing a cognitive task. A goal function for treadmill walking was first defined, i.e., maintain constant speed at each step, which led to a goal equivalent manifold (GEM) containing all combinations of step time and step length that equally satisfied the function. Given the GEM, amounts of goal-equivalent and non-goal-equivalent variability were afterwards determined and used to define an index providing information about the set of effective motor solutions relative to the GEM. The set was limited in OA compared to YA in treadmill walking alone, indicating that OA made less flexible use of motor abundance than YA. However, this differentiation between YA and OA disappeared when concurrently performing the cognitive task. It is proposed that OA might have benefited from cognitive compensation.
PMCID: PMC3401175  PMID: 22911777
18.  Angiotensin-converting Enzyme Inhibitor and Statin Medication Use and Incident Mobility Limitation in Community Older Adults. The Health, Aging and Body Composition Study 
Angiotensin-converting enzyme (ACE) inhibitors and statin medications have been proposed as potential agents to prevent or delay physical disability; yet limited research has evaluated whether such use in older community dwelling adults is associated with a lower risk of incident mobility limitation.
Longitudinal cohort study
Health, Aging and Body Composition (Health ABC)
3055 participants who were well functioning at baseline (e.g., no mobility limitations).
Summated standardized daily doses (low, medium and high) and duration of ACE inhibitor and statin use was computed. Mobility limitation (two consecutive self-reports of having any difficulty walking 1/4 mile or climbing 10 steps without resting) was assessed every 6 months after baseline. Multivariable Cox proportional hazard analyses were conducted adjusting for demographics, health status, and health behaviors.
At baseline, ACE inhibitors and statins were used by 15.2% and 12.9%, respectively and both increased to over 25% by year 6. Over 6.5 years of follow-up, 49.8% had developed mobility limitation. In separate multivariable models, neither ACE inhibitor (multivariate hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.82–1.09) nor statin use (multivariate HR 1.02; 95% CI 0.87–1.17) was associated with a lower risk for mobility limitation. Similar findings were seen in analyses examining dose- and duration-response relationships and sensitivity analyses restricted to those with hypertension.
These findings indicate that ACE inhibitors and statins widely prescribed to treat hypertension and hypercholesterolemia, respectively do not lower risk of mobility limitation, an important life quality indicator.
PMCID: PMC3389784  PMID: 22092102
19.  A protocol for a randomized clinical trial of interactive video dance: potential for effects on cognitive function 
BMC Geriatrics  2012;12:23.
Physical exercise has the potential to affect cognitive function, but most evidence to date focuses on cognitive effects of fitness training. Cognitive exercise also may influence cognitive function, but many cognitive training paradigms have failed to provide carry-over to daily cognitive function. Video games provide a broader, more contextual approach to cognitive training that may induce cognitive gains and have carry over to daily function. Most video games do not involve physical exercise, but some novel forms of interactive video games combine physical activity and cognitive challenge.
This paper describes a randomized clinical trial in 168 postmenopausal sedentary overweight women that compares an interactive video dance game with brisk walking and delayed entry controls. The primary endpoint is adherence to activity at six months. Additional endpoints include aspects of physical and mental health. We focus this report primarily on the rationale and plans for assessment of multiple cognitive functions.
This randomized clinical trial may provide new information about the cognitive effects of interactive videodance. It is also the first trial to examine physical and cognitive effects in older women. Interactive video games may offer novel strategies to promote physical activity and health across the life span.
The study is IRB approved and the number is: PRO08080012 Identifier: NCT01443455
PMCID: PMC3404007  PMID: 22672287
20.  Pupillary unrest correlates with arousal symptoms and motor signs in Parkinson disease 
Arousal symptoms (e.g., sleepiness) are common in Parkinson disease and pupillary unrest (spontaneous changes in pupil diameter) is positively associated with sleepiness. We explored pupillary unrest in Parkinson disease.
Arousal symptoms (Epworth sleepiness scale and sleep/fatigue domain of the non-motor symptoms scale for Parkinson disease (NMS-sleep)) and pupillary unrest were assessed in 31 participants (14 PD, 17 controls). Effect sizes and t-tests compared Parkinson disease with control participants. Correlation coefficients were calculated among arousal symptoms, pupillary unrest and UPDRS-III. Linear regression was performed with arousal symptoms or pupillary unrest as outcome.
Parkinson disease participants reported more arousal symptoms than controls. Pupillary unrest, arousal symptoms and UPDRS-III were positively correlated. The association between NMS-sleep score and pupillary unrest was higher in Parkinson disease versus controls, and higher in those with more Parkinsonian motor signs. UPRDS-III was positively associated with pupillary unrest.
Pupillary unrest correlates with motor and non-motor features associated with Lewy-related pathology, suggesting it may be a non-motor marker of progression in Parkinson disease.
PMCID: PMC3119728  PMID: 21506163
non-motor features; Parkinson disease; pupillography; pupil; sleep disorders; autonomic dysfunction
21.  Ability to Walk 1/4 Mile Predicts Subsequent Disability, Mortality, and Health Care Costs 
Mobility, such as walking 1/4 mile, is a valuable but underutilized health indicator among older adults. For mobility to be successfully integrated into clinical practice and health policy, an easily assessed marker that predicts subsequent health outcomes is required.
To determine the association between mobility, defined as self-reported ability to walk 1/4 mile, and mortality, functional decline, and health care utilization and costs during the subsequent year.
Analysis of longitudinal data from the 2003–2004 Medicare Current Beneficiary Survey, a nationally representative sample of Medicare beneficiaries.
Participants comprised 5895 community-dwelling adults aged 65 years or older enrolled in Medicare.
Main Measures
Mobility (self-reported ability to walk 1/4 mile), mortality, incident difficulty with activities of daily living (ADLs), total annual health care costs, and hospitalization rates.
Key Results
Among older adults, 28% reported difficulty and 17% inability to walk 1/4 mile at baseline. Compared to those without difficulty and adjusting for demographics, socioeconomic status, chronic conditions, and health behaviors, mortality was greater in those with difficulty [AOR (95% CI): 1.57 (1.10-2.24)] and inability [AOR (CI): 2.73 (1.79-4.15)]. New functional disability also occurred more frequently as self-reported ability to walk 1/4 mile declined (subsequent incident disability among those with no difficulty, difficulty, or inability to walk 1/4 mile at baseline was 11%, 29%, and 47% for instrumental ADLs, and 4%, 14%, and 23% for basic ADLs). Total annual health care costs were $2773 higher (95% CI $1443-4102) in persons with difficulty and $3919 higher (CI $1948-5890) in those who were unable. For each 100 persons, older adults reporting difficulty walking 1/4 mile at baseline experienced an additional 14 hospitalizations (95% CI 8-20), and those who were unable experienced an additional 22 hospitalizations (CI 14-30) during the follow-up period, compared to persons without walking difficulty.
Mobility disability, a simple self-report measure, is a powerful predictor of future health, function, and utilization independent of usual health and demographic indicators. Mobility disability may be used to target high-risk patients for care management and preventive interventions.
PMCID: PMC3019329  PMID: 20972641
aging; mobility; mortality; disability; health care costs
22.  Autonomic Insufficiency in Pupillary and Cardiovascular Systems in Parkinson's Disease 
Parkinsonism & related disorders  2010;17(2):119-122.
In Parkinson's disease (PD), neurodegenerative changes have been observed in autonomic pathways involving multiple organ systems. We explore pupillary and cardiac autonomic measures as physiological manifestations of PD neurodegeneration.
Pupil measures (pupillary unrest (spontaneous changes of pupil diameter in darkness), constriction velocity and redilation velocity) were assessed in 35 participants (17 PD, 18 controls). Simultaneous cardiac measures (respiratory sinus arrythmia during deep breathing, Valsalva ratio, resting heart rate variability (HRV), orthostatic change in blood pressure and orthostatic change in heart rate) were obtained. Nonparametric statistics were used to compare PD with control participants and to calculate correlation coefficients between pupillary and cardiac measures.
Pupillary unrest and orthostatic decreases in systolic blood pressure were greater in PD than controls. Respiratory sinus arrythmia during deep breathing and resting HRV were lower in PD. Among all participants, there was a negative correlation between HRV and redilation velocity and a positive correlation between orthostatic change in heart rate and pupillary unrest. A modifying effect of PD was found on the association between high frequency HRV and pupillary unrest.
Results demonstrate simultaneous autonomic dysfunction in both pupillary and cardiac systems in PD. The correlations between pupillary and cardiac measures suggest shared central centers of autonomic integration, while the modifying effect of PD may reflect autonomic effects of PD-related pathology not present in controls.
PMCID: PMC3034773  PMID: 21115264
non-motor features; Parkinson's disease; pupillography; pupil; cardiac physiology; autonomic dysfunction
23.  Successful Aging as a Continuum of Functional Independence: Lessons from Physical Disability Models of Aging 
Aging and Disease  2011;3(1):5-15.
Successful aging is a multidimensional construct that could be viewed as a continuum of achievement. Based on the disability model proposed by the WHO International Classification of Functioning, Disability and Health, successful aging includes not only the presence or absence of disease, but also aspects of mobility and social participation. Here we review definitions of successful aging and discuss relevance of the disability model in the evaluation of successful aging and frailty. In particular, we summarize evidences that highlight the importance of measures of mobility (ability to walk and perform activities of daily living), and social participation in identifying and locating older adults across the range of the successful aging continuum. Lastly, we discuss the role of inflammation in age-related decline and in frailty. Future research directions are proposed, including identifying causal pathways among inflammatory markers, disability, and frailty. A better understanding of immunological functioning in late life may help unlock novel ways to promote successful aging.
PMCID: PMC3320804  PMID: 22500268
mobility; participation; frailty; inflammation
24.  Validation of a Measure of Smoothness of Walking 
Altered biomechanics and/or neural control disrupt the timing of postures and muscle patterns necessary for smooth and regular stepping. Harmonic ratio of trunk accelerations has been proposed as a measure of smoothness of walking. We sought to validate this measure of smoothness by examining the measure in groups expected to differ in smoothness (ie, young and old) and across walking conditions expected to affect smoothness (ie, straight path, curved path, and dual task).
Thirty young (mean age = 24.4 ± 4.3 years) and 30 older adults (mean age = 77.5 ± 5.1 years) who could ambulate independently participated. We measured linear acceleration of the body along vertical, anterior-posterior, and medial–lateral axes using a triaxial accelerometer firmly attached to the skin over the L3 segment of the lumbar spine during straight path, curved path, and dual task (reciting every other letter of the alphabet) walking.
Older adults had lower harmonic ratio anterior-posterior (HRAP), that is, were less smooth in the direction of motion and walked more slowly than young adults for all walking conditions. Once the analyses were adjusted for walking speed, only HRAP differed between young and old participants for all walking conditions. For the most part, both young and old participants were less smooth for slow pace walking, curved path walking, and dual task walking compared with usual pace straight path walking.
The harmonic ratio, calculated from trunk acceleration, is a valid measure of smoothness of walking, which may be thought of as a measure of the motor control of walking.
PMCID: PMC3032432  PMID: 20923910
Gait; Smoothness; Accelerometer
25.  Psychomotor Speed and Functional Brain MRI 2 Years After Completing a Physical Activity Treatment 
Short-term adherence to physical activity (PA) in older adults improves psychomotor processing abilities and is associated with greater brain activation. It is not known whether these associations are also significant for longer-term adherence to moderate-intensity activities.
We measured the cross-sectional association of regular walking with brain activation while performing the digit symbol substitution test (DSST). Participants of the lifestyle interventions and independence for elders—pilot study were examined 2 years after completing a 1-year treatment, consisting of either PA or education in successful aging (SA). Data were obtained from 20 PA participants who reported having remained active for 2 years after the end of the treatment and from 10 SA participants who reported having remained sedentary during the same period (mean age: 81.5 and 80.8 years). Complete brain activation and behavioral data were available for 17 PA and 10 SA participants.
Two years after the formal intervention had ended, the PA group engaged in more minutes of moderate activity and had significantly greater DSST score and higher brain activation within regions important for processing speed (left dorsolateral prefrontal, posterior parietal, and anterior cingulate cortices). Associations were independent of self-reported health, blood pressure, cognition, medication records, gray matter atrophy, and white matter hyperintensities.
Persistent engagement in PA may have beneficial effects on psychomotor processing speed and brain activation, even for moderate levels and even when started late in life. Future studies are warranted to assess whether these beneficial effects are explained by delayed neuronal degeneration and/or new neurogenesis.
PMCID: PMC2869531  PMID: 20348185
Physical activity; Sedentary; fMRI; Executive control function; Older adults

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