Baseline Gait Speed Research Articles

Circulating Procollagen Type III N-Terminal Peptide and Physical Function in the Long Life Family Study

Circulating levels of procollagen type III N-terminal peptide (P3NP) may reflect increased fibrosis of skeletal muscle and other tissues with aging. In the current study, we tested if P3NP levels were associated with baseline and 7-year change in physical function among adults aged 39-104. Participants (n=400) were from the Long Life Family Study, a study of exceptional familial longevity. Plasma P3NP concentration was measured using a sandwich enzyme-linked immunosorbent assay (inter-assay CVs <3%). At baseline and 7-year follow-up visits, physical function was measured using the Short Physical Performance Battery (score 0-12), which consists of gait speed, balance, and chair-rise tests. Grip strength was measured using a handheld dynamometer. The association between log-transformed P3NP and physical function was examined using Generalized Estimating Equations adjusted for familial relatedness, age, sex, height, weight, lifestyle characteristics, chronic disease prevalence and inflammatory cytokines. Participants were aged 73.1 ± 15.2 years, 54% female, had a BMI of 26.6 ± 4.3 kg/m2, and a gait speed of 1.0 ± 0.3 m/s. One standard deviation higher P3NP concentration was related to worse baseline SPPB score (β=-0.9points), gait speed (β=-0.05m/s), chair-rise time (β=8.34seconds), and grip strength (β=-2.0kg; all p<0.001). Higher P3NP concentration was also associated with greater declines in gait speed (β=-1.41, p<.001) and chair-rise performance (β=0.41, p<.001). Plasma P3NP concentration may be a strong, novel biomarker of current and physical function changes with aging. Future research is needed to extend our findings to a larger population, and determine the mechanisms underlying these associations.

Metrics of Phenotypic Aging From the Energetics Perspective

Identifying the most critical metrics of aging is an ongoing challenge due to a lack of comprehensive measurements and heterogeneity of the aging process. Using the Baltimore Longitudinal Study of Aging, we developed a conceptual framework to identify metrics of aging that capture the hierarchical and temporal relationships between functional aging, phenotypic aging, and biological aging based on four hypothesized domains: energy regulation, body composition, homeostatic mechanisms, and neurodegeneration. Focusing on the energetics domain, we examined trajectories of eight phenotypes using more than 10 years of longitudinal data. The standardized Cronbach’s alpha for these variables was 0.80, providing construct validity of our concept. We further implemented item response theory to integrate these phenotypes into a summarized energy score. Linear mixed models were used to assess the cross-sectional and longitudinal associations between the summarized energy score and physical functioning as measured by gait speed and time to walk 400m as quickly as possible (number of participants ~ 811, number of observations ~ 1700). After adjusting for age, sex, weight, and height, a higher summarized energy score was independently associated with faster baseline gait speed (0.13 m/s, p<0.001 ) and faster 400m time (-35.3 seconds, p<0.001), and longitudinally associated with slower gait speed decline (0.08 m/s/decade, p<0.001) and slower 400m time increase (-37.8 secs/decade, p<0.001). This work demonstrates the utility of our energetics domain-based summarized score. Moving forward, it will be important to clarify relationships between this summarized score and other functional metrics and assess its generalizability to the other cohorts.

Deterioration in Motor Function Over Time in Older Adults With Type 2 Diabetes is Associated with Accelerated Cognitive Decline

Type 2 diabetes (T2D) is associated with motor impairments and a higher dementia risk. The relationships of motor decline with cognitive decline in T2D older adults has rarely been studied. Using data from the Israel Diabetes and Cognitive Decline study (N = 892), we examined associations of decline in motor function with cognitive decline over a 54-month period. Motor function measures were strength (handgrip) and gait speed (time to walk 3 m). Participants completed a neuropsychologic battery of 13 tests transformed into z-scores, summarized into 4 cognitive domains: episodic memory, attention/working memory, executive functions, and language/semantic categorization. The average of the 4 domains' z-scores defined global cognition. Motor and cognitive functions were assessed in 18-months intervals. A random coefficients model delineated longitudinal relationships of cognitive decline with baseline and change from baseline in motor function, adjusting for sociodemographic, cardiovascular, and T2D-related covariates. Slower baseline gait speed levels were significantly associated with more rapid decline in global cognition (P = .004), language/semantic categorization (P = .006) and episodic memory (P = .029). Greater decline over time in gait speed was associated with an accelerated rate of decline in global cognition (P = .050), attention/working memory (P = .047) and language/semantic categorization (P<.001). Baseline strength levels were not associated with cognitive decline but the rate of declining strength was associated with an accelerated decline in executive functions (P = .025) and language/semantic categorization (P = .006). In T2D older adults, the rate of decline in motor function, beyond baseline levels, was associated with accelerated cognitive decline, suggesting that cognitive and motor decline share common neuropathologic mechanisms in T2D.

Association between neuromelanin-sensitive MRI signal and psychomotor slowing in late-life depression.

Late-life depression (LLD) is a prevalent and disabling condition in older adults that is often accompanied by slowed processing and gait speed. These symptoms are related to impaired dopamine function and sometimes remedied by levodopa (L-DOPA). In this study, we recruited 33 older adults with LLD to determine the association between a proxy measure of dopamine function-neuromelanin-sensitive magnetic resonance imaging (NM-MRI)-and baseline slowing measured by the Digit Symbol test and a gait speed paradigm. In secondary analyses, we also assessed the ability of NM-MRI to predict L-DOPA treatment response in a subset of these patients (N = 15) who received 3 weeks of L-DOPA. We scanned a further subset of these patients (N = 6) with NM-MRI at baseline and after treatment to preliminarily evaluate the effects of L-DOPA treatment on the NM-MRI signal. We found that lower baseline NM-MRI correlated with slower baseline gait speed (346 of 1807 substantia nigra-ventral tegmental area (SN-VTA) voxels, Pcorrected = 0.038), particularly in the more medial, anterior, and dorsal SN-VTA. Secondary analyses failed to show an association between baseline NM-MRI and treatment-related changes in gait speed, processing speed, or depression severity (all Pcorrected > 0.361); we however found preliminary evidence of increases in the NM-MRI signal 3 weeks post-treatment with L-DOPA compared to baseline (200 of 1807 SN-VTA voxels; Pcorrected = 0.046), although the small sample size of these preliminary analyses warrants caution in their interpretation and future replications. Overall, our findings indicate that NM-MRI is sensitive to variability in gait speed in patients with LLD, suggesting this non-invasive MRI measure may provide a promising marker for dopamine-related psychomotor slowing in geriatric neuropsychiatry.

Circulating Procollagen Type III N-Terminal Peptide and Physical Function in Adults from the Long Life Family Study.

Circulating levels of procollagen type III N-terminal peptide (P3NP) may reflect increased fibrosis of skeletal muscle and other tissues with aging. Herein, we tested if P3NP was associated with baseline and 7-year change in physical function. Participants (n = 400) were from the Long Life Family Study, a study of exceptional familial longevity. Plasma P3NP concentration was measured using a sandwich enzyme-linked immunosorbent assay (inter-assay coefficient of variation <5.5%). At baseline and 7-year follow-up visits, physical function was measured using the Short Physical Performance Battery (SPPB score 0-12), which consists of gait speed, balance, and chair-rise tests. Grip strength was measured using a handheld dynamometer. The association between log-transformed P3NP and physical function was examined using generalized estimating equations adjusted for familial relatedness, age, sex, height, weight, lifestyle characteristics, liver function, kidney function, lung function, and chronic disease prevalence. Participants were aged 73.1 ± 15.2 years (range: 39-104), 54% female, had body mass index of 26.6 ± 4.3 kg/m2, and gait speeds of 1.0 ± 0.3 m/s. One standard deviation higher log-transformed P3NP was related to worse baseline SPPB score (β = -0.9points), gait speed (β = -0.05m/s), chair-rises per-second (β = -0.46chair-rises/10 seconds), and grip strength (β = -2.0kg; all p < .001). Higher P3NP was also associated with greater declines in gait speed (β = -1.41, p < .001) and transitioning to being unable to perform chair-rises (β = 0.41, p < .001) after 7 years. Plasma P3NP may be a strong, novel biomarker of current and future physical function. Future research is needed to extend our findings to other cohorts and determine mechanisms underlying these associations.

Mobility Impairment in Patients New to Dialysis

Background: Impaired mobility is associated with functional dependence, frailty, and mortality in prevalent patients undergoing dialysis. We investigated risk factors for mobility impairment, (poor gait speed) in patients incident to dialysis, and changes in gait speed over time in a 2-year longitudinal study. Methods: One hundred eighty-three patients enrolled within 6 months of dialysis initiation were followed up 6, 12, and 24 months later. Grip strength, health-related quality of life, and comorbidities were assessed at baseline. Outcomes were (a) baseline gait speed and (b) change in gait speed over time. Gait speed was assessed by 4-meter walk. Multivariate linear regression was used to identify risk factors for low gait speed at baseline. For longitudinal analyses, linear mixed effects modeling with gait speed modeled over time was used as the outcome. Results: Participants were 54.7 ± 12.8 years old, 52.5% men, 73.9% black with mean dialysis vintage of 100.1 ± 46.9 days and median gait speed 0.78 (0.64–0.094) m/s. Lower health utility and grip strength, diabetic nephropathy, and walking aids were associated with lower baseline gait speed. Loss of 0.1 m/s gait speed occurred in 24% of subjects at 1 year. In multivariate mixed effects models, only age, walking aid use, lower health utility, and lower handgrip strength were significantly associated with gait speed loss. Conclusions: In our cohort of incident dialysis patients, overall gait speed is very low and 54.2% of the subjects continue to lose gait speed over 2 years. Older age, lower handgrip strength, and quality of life are risk factors for slowness. Patients at highest risk of poor gait speed can be identified at dialysis initiation to allow targeted implementation of therapeutic options.

Physical Function Assessment in Older Hemodialysis Patients

Physical function is not routinely measured in older adults receiving dialysis. We evaluated the appropriateness of repeated measurements of physical function, including Short Physical Performance Battery (SPPB), handgrip strength, and activities of daily living (ADLs), in older adults receiving dialysis. Prospective study. 37 community-dwelling adults 65 years and older receiving in-center hemodialysis at 5 dialysis units located in North Carolina. SPPB (an assessment of standing balance, chair stands, and gait speed), handgrip strength, and Katz and Lawton ADLs at baseline and subsequent 3-month intervals up to 6 months. Completion rate, presence of floor or ceiling effects, and presence of clinically meaningful change in physical function measurements. Of 55 potential participants, we enrolled 37 (67%) older adults receiving hemodialysis. Among 35 enrolled participants who completed baseline assessment in a dialysis unit, mean age was 70.1 (SD, 5) years, 46% (n=16) were women, 77% (n=27) were African American, and median time receiving dialysis was 2.7 (IQR, 0.6-5.0) years. There were 3 deaths within the observation period, and study retention at 3 and 6 months was 83% (n=29) and 74% (n=26), respectively. Participants tolerated measurements; only 2 participants did not attempt 1 of the performance-based tests at a study visit. Baseline median SPPB score, grip strength, and gait speed were 6 (IQR, 4-9), 55 (IQR, 42-70) kg, and 0.76 (IQR, 0.46-0.86) m/s, respectively. Baseline median for Katz and Lawton ADLs were 6 (IQR, 6-6) and 7 (IQR, 4-8), respectively; ceiling effects were observed for both measures. For some participants, clinically meaningful changes (improvement or decline) in SPPB score, grip strength, and gait speed occurred at each 3-month interval. Limited geographic and ethnic variation. SPPB, handgrip strength, and gait speed alone are appropriate measures for interval physical function assessment in community-dwelling older adults receiving in-center hemodialysis.

Serum metabolites associate with physical performance among middle-aged adults: Evidence from the Bogalusa Heart Study.

Age-related declines in physical performance predict cognitive impairment, disability, chronic disease exacerbation, and mortality. We conducted a metabolome-wide association study of physical performance among Bogalusa Heart Study participants. Bonferroni corrected multivariate-adjusted linear regression was employed to examine cross-sectional associations between single metabolites and baseline gait speed (N=1,227) and grip strength (N=1,164). In a sub-sample of participants with repeated assessments of gait speed (N=282) and grip strength (N=201), significant metabolites from the cross-sectional analyses were tested for association with change in physical performance over 2.9 years of follow-up. Thirty-five and seven metabolites associated with baseline gait speed and grip strength respectively, including six metabolites that associated with both phenotypes. Three metabolites associated with preservation or improvement in gait speed over follow-up, including: sphingomyelin (40:2) (P=2.6×10-4) and behenoyl sphingomyelin (d18:1/22:0) and ergothioneine (both P<0.05). Seven metabolites associated with declines in gait speed, including: 1-carboxyethylphenylalanine (P=8.8×10-5), and N-acetylaspartate, N-formylmethionine, S-adenosylhomocysteine, N-acetylneuraminate, N2,N2-dimethylguanosine, and gamma-glutamylphenylalanine (all P<0.05). Two metabolite modules reflecting sphingolipid and bile acid metabolism associated with physical performance (minimum P=7.6×10-4). These results add to the accumulating evidence suggesting an important role of the human metabolome in physical performance and specifically implicate lipid, nucleotide, and amino acid metabolism in early physical performance decline.

1462-P: Baseline Gait Speed Can Predict Diabetes Incidence in Individuals with or at Risk of Knee Osteoarthritis: A Longitudinal Study Using Data from the Osteoarthritis Initiative

Introduction: The coexistence of Knee osteoarthritis (OA) and diabetes mellitus (DM) can be explained by shared risk factors such as age and obesity. Both conditions adversely affect gait speed, however, longitudinal studies investigating the relationship between gait speed and DM incidence in people with or at elevated risk for knee OA are lacking. Therefore, the aim was to investigate the association between baseline gait speed and risk of DM incidence among people with or at risk for knee OA. Methods: Participants from the osteoarthritis initiative, aged 45 to 79 years, who were at risk or had knee OA and followed up from baseline to 96-month visit were included. Self-reported diabetes was used over a 4-time points to identify DM incidence. Gait speed was measured at baseline using 20 meter walk test. Body mass index (BMI) was measured and included as a time-dependent covariate. Generalized estimating equations with logistic regression were utilized to examine the association between baseline gait speed and DM incidence. Results: Increased baseline gait speed was significantly associated with decreased odds of incident DM after adjustments for covariates (OR 0.52). The risk of DM incidence decreased 48% for each 0.1 m/s increase in gait speed at baseline for individuals with established or at risk of knee OA. Sensitivity analysis showed that the significant results were maintained with those at risk of OA (OR 0.45) but not in those with established knee OA. Conclusion: Increasing baseline gait speed in general was significantly associated with a lower risk of DM incidence over time. However, the association disappeared after adjustments for BMI in people with established knee OA, suggesting that the majority of this association might be explained by higher weight. Therefore, future research should examine closely the link between gait speed and well-defined DM risk using objective measures such as glucose level. Disclosure A.M. Alenazi: None. B. Alqahtani: None. M.M. Alshehri: None. A.D. Alanazi: None. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. V. Vennu: None. N.A. Segal: None. S.M. Bindawas: None.

Gait speed, cognition and falls in people living with mild-to-moderate Alzheimer disease: data from NILVAD

BackgroundPrevious evidence suggests that slower gait speed is longitudinally associated with cognitive impairment, dementia and falls in older adults. Despite this, the longitudinal relationship between gait speed, cognition and falls in those with a diagnosis of dementia remains poorly explored. We sought to assess this longitudinal relationship in a cohort of older adults with mild to-moderate Alzheimer Disease (AD).MethodsAnalysis of data from NILVAD, an 18-month randomised-controlled trial of Nilvadipine in mild to moderate AD. We examined: (i) the cross-sectional (baseline) association between slow gait speed and cognitive function, (ii) the relationship between baseline slow gait speed and cognitive function at 18 months (Alzheimer Disease Assessment Scale, Cognitive Subsection: ADAS-Cog), (iii) the relationship between baseline cognitive function and incident slow gait speed at 18 months and finally (iv) the relationship of baseline slow gait speed and incident falls over the study period.ResultsOverall, one-tenth (10.03%, N = 37/369) of participants with mild-to-moderate AD met criteria for slow gait speed at baseline and a further 14.09% (N = 52/369) developed incident slow gait speed at 18 months. At baseline, there was a significant association between poorer cognition and slow gait speed (OR 1.05, 95% CI 1.01–1.09, p = 0.025). Whilst there was no association between baseline slow gait speed and change in ADAS-Cog score at 18 months, a greater cognitive severity at baseline predicted incident slow gait speed over 18 months (OR 1.04, 1.01–1.08, p = 0.011). Further, slow gait speed at baseline was associated with a significant risk of incident falls over the study period, which persisted after covariate adjustment (IRR 3.48, 2.05–5.92, p < 0.001).ConclusionsPoorer baseline cognition was associated with both baseline and incident slow gait speed. Slow gait speed was associated with a significantly increased risk of falls over the study period. Our study adds further evidence to the complex relationship between gait and cognition in this vulnerable group and highlights increased falls risk in older adults with AD and slow gait speed.Trial registrationSecondary analysis of the NILVAD trial (Clincaltrials.gov NCT02017340; EudraCT number 2012–002764-27). First registered: 20/12/2013.

Gait and fate: Baseline gait speed and mortality after transcatheter aortic valve implantation

BackgroundTo determine whether baseline gait speed predicts mortality after transcatheter aortic valve implantation (TAVI), a meta-analysis of currently available studies was performed. MethodsTo identify all studies researching the impact of preprocedural gait speed on mortality after TAVI, PubMed and Web of Science were searched through May 2019. Adjusted (if unavailable, unadjusted) hazard/odds ratios (ORs/HRs) with their confidence interval of mortality for slow (if available, the slowest) versus fast (if available, the fastest) gait speed (with cut-off values defined in each study) and those for unable to walk versus walker (if available, with the fastest gait speed) were extracted from each study, and then separately pooled by means of inverse variance-weighted averages of logarithmic ORs/HRs in the random-effects model. ResultsTwelve eligible studies (7 and 5 based on the distance-limited and time-limited walk test, respectively) were identified and integrated in the present meta-analysis. The pooled analysis of all ORs/HRs demonstrated that slow walkers (primary meta-analysis; OR/HR, 2.38; p < 0.00001) and unable to walk (OR/HR, 1.75; p = 0.01) were significantly associated with increased mortality. The subgroup analysis for the primary meta-analysis indicated no significant subgroup difference between studies utilizing the 4-m/5-m/15-foot walk test and those applying the 6-min walk test (p = 0.45). Combining studies with 1-year follow-up did not alter the primary result (p < 0.0001). Pooling studies with adjusted ORs/HRs did not change the principal result (p = 0.0002). No funnel plot asymmetry for the primary meta-analysis was identified. ConclusionsSlow baseline gait speed (and unable to walk) is associated with increased mortality after TAVI.

Association of Dual Decline in Memory and Gait Speed With Risk for Dementia Among Adults Older Than 60 Years

Dual decline in both memory and gait speed may characterize a group of older individuals at high risk for future dementia. To assess the risk of dementia in older persons who experience parallel declines in memory and gait speed compared with those who experience no decline or decline in either memory or gait speed only. A multicohort meta-analysis was performed of 6 prospective cohort studies conducted between 1997 and 2018 in the United States and Europe. Participants were 60 years or older, had an initial gait speed of more than 0.6 m/s (ie, free of overt dismobility), with repeated measures of memory and gait speed before dementia diagnosis during a mean follow-up of 6.6 to 14.5 years. Within each study, participants were divided into 4 groups: memory decline only, gait speed decline only, dual decline, or no decline (hereafter referred to as usual agers). Gait decline was defined as a loss of 0.05 m/s or more per year; memory decline was defined as being in the cohort-specific lowest tertile of annualized change. Risk of incident dementia according to group membership was examined by Cox proportional hazards regression with usual agers as the reference, adjusted for baseline age, sex, race/ethnicity, educational level, study site, and baseline gait speed and memory. Across the 6 studies of 8699 participants, mean age ranged between 70 and 74 years and mean gait speed ranged between 1.05 and 1.26 m/s. Incident dementia ranged from 5 to 21 per 1000 person-years. Compared with usual agers, participants with only memory decline had 2.2 to 4.6 times higher risk for developing dementia (pooled hazard ratio, 3.45 [95% CI, 2.45-4.86]). Those with only gait decline had 2.1 to 3.6 times higher risk (pooled hazard ratio, 2.24 [95% CI, 1.62-3.09]). Those with dual decline had 5.2 to 11.7 times the risk (pooled hazard ratio, 6.28 [95% CI, 4.56-8.64]). In this study, dual decline of memory and gait speed was associated with increased risk of developing dementia among older individuals, which might be a potentially valuable group for preventive or therapeutic interventions. Why dual decline is associated with an elevated risk of dementia and whether these individuals progress to dementia through specific mechanisms should be investigated by future studies.

Neuroanatomical predictors of L-DOPA response in older adults with psychomotor slowing and depression: A pilot study

Declining function in dopamine circuits is implicated in normal aging and late-life depression (LLD). Dopamine augmentation recently has shown therapeutic promise, but predictors of response are unknown. Depressed elders with slowed gait underwent baseline magnetic resonance imaging (MRI) and [11C]raclopride positron emission tomography (PET). Subjects then received open treatment with carbidopa/levodopa (L-DOPA) for three weeks. Linear regressions examined relationships between baseline MRI measures, [11C]raclopride binding, and behavioral outcomes. Among N=16 participants aged 72.5±6.8 years, higher left superior temporal gyrus volume was associated with higher processing speed at baseline, while cortical thinning in a processing speed network was associated with greater improvement following L-DOPA. Greater volume and cortical thickness in brain regions associated with mobility were associated with higher baseline gait speed. Higher baseline white matter hyperintensity volume predicted less post-L-DOPA improvement on dual task gait speed and IDS-SR scores. Higher [11C]raclopride binding in the associative striatum was associated with cortical thickness in some, but not all, processing speed brain regions, while higher binding in sensorimotor striatum was significantly associated with left caudate volume. Limiting the conclusions drawn from this pilot study are the small sample size and open administration of L-DOPA. Greater baseline brain volumes and cortical thickness in regions supporting cognition and gait were associated with higher behavioral performance, while lower structural integrity was associated with increased responsivity to L-DOPA. If substantiated in larger studies, these findings could facilitate the targeting of dopaminergic treatments to those LLD patients most likely to respond.

Predialysis fluid overload and gait speed: a repeated measures analysis among patients on chronic dialysis.

Slow gait speed is associated with hospitalization and death. We examined whether predialysis fluid overload contributes to gait speed impairment. We measured predialysis gait speed at baseline and 12 and 24 months among 298 patients recruited in the A Cohort Study to Investigate the Value of Exercise in ESRD/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD. We used multivariable linear mixed modeling to examine associations between patient data and gait speed. We then added either bioimpedance-estimated volume of predialysis fluid overload or volume of delivered ultrafiltration to ascertain whether fluid excess was associated with gait speed and its trajectory. We also tested whether fluid overload change with time was predictive of gait speeds. The mean baseline gait speed was 1.01 m/s and it declined by an average of 0.08 m/s/year. Older age, nonwhite race, Hispanic ethnicity, diabetes, recent fall, recent hospitalization, tobacco use and lower serum albumin were associated with slower gait speed. Each liter of predialysis fluid overload was associated with a 0.02 m/s slower gait speed [95% confidence interval (CI) 0.01-0.04, P = 0.008] and 0.05 m/s additional slowing per year (95% CI 0.03-0.06, P < 0.0001). Higher ultrafiltration volumes were associated with 0.07 m/s slower gait speed per 3% body weight removed (0.002-0.14, P = 0.045) but not with gait speed trajectory (P = 0.08). Patients who increased fluid overload walked 0.08 m/s slower compared with those who decreased fluid overload (95% CI 0.003-0.15, P = 0.04). Predialysis fluid overload was associated with slower gait speed and gait speed decline over time. Interventions that limit fluid overload may lead to improvements in physical performance.

GENOME-WIDE LINKAGE ANALYSIS IDENTIFIES A NOVEL LOCUS FOR LONGITUDINAL GAIT SPEED CHANGE WITH AGING

Gait speed is an indicator of health and function with aging. The potential genetic contributions to gait speed and its decline with aging are not well characterized. We sought to better quantify the genetic contributions to and identify potential genes and genetic variants underlying change in gait speed among older adults. To accomplish these aims, we used data from 2379 individuals belonging to 509 families in the Long Life Family Study (mean age 64 ± 12, range 30–110 years; 45% men). Gait-speed was measured over 4 meters at baseline and after an average of 7±1.1 years. Quantitative trait linkage analyses were completed using pedigree-based maximum-likelihood methods with logarithm of the odds (LOD) scores > 3.3 indicating genome-wide significance. We also performed linkage analysis in the top 10% of families contributing to LOD scores to allow for heterogeneity among families (HLOD). Data were adjusted for age, sex, height and field center. At baseline, 26.9% of individuals had “low” gait-speed <1.0 m/s (mean: 1.1±0.2 m/s) and gait speed declined at a rate of -0.02±0.03 m/s per year (p<0.0001). Baseline and change in gait-speed were significantly heritable (h2 = 0.24-0.32, p<0.05). We did not find significant evidence for linkage for baseline gait speed; however, we identified a potentially novel locus for change in gait speed on chromosome 16p (LOD 4.2). A subset of 21 families contributed to this linkage peak (HLOD = 6.83). Sequence analysis of the chromosome 16 region may yield new insight on the biology of age-related mobility decline.

Mortality Risk Among Older People Who Did Versus Did Not Sustain a Fracture: Baseline Prefracture Strength and Gait Speed as Predictors in a 15-Year Follow-Up.

Physiological reserve, as indicated by muscle strength and gait speed, may be especially determinant of survival in people who are exposed to a health stressor. We studied whether the association between strength/speed and mortality risk would be stronger in the time period after a fracture compared to other time periods. Participants were population-based sample of 157 men and 325 women aged 75 and 80 years at baseline. Maximal 10-m gait speed and maximal isometric grip and knee extension strength were tested at the baseline before the fracture. Subsequent fracture incidence and mortality were followed up for 15 years. Cox regression analysis was used to estimate fracture time-stratified effects of gait speed and muscle strength on mortality risk in three states: (i) nonfracture state, (ii) the first postfracture year, and (iii) after the first postfracture year until death/end of follow-up. During the follow-up, 20% of the men and 44% of the women sustained a fracture. In both sexes, lower gait speed and in women lower knee extension strength was associated with increased mortality risk in the nonfracture state. During the first postfracture year, the mortality risk associated with slower gait and lower strength was increased and higher than in the nonfracture state. After the first postfracture year, mortality risk associated with lower gait speed and muscle strength attenuated. Lower gait speed and muscle strength were more strongly associated with mortality risk after fracture than during nonfracture time, which may indicate decreased likelihood of recovery.

Association of Antidepressants With Recurrent, Injurious and Unexplained Falls is Not Explained by Reduced Gait Speed

To examine if antidepressants at baseline are associated with falls and syncope over 4 years follow-up and if any observed associations are explained by baseline gait speed. Longitudinal study (three waves). The Irish Longitudinal Study on Ageing (TILDA), a nationally representative cohort study. Two thousand ninety-three community-dwelling adults aged ≥60 years. Antidepressants (ATC code "N06A") were identified. Recurrent falls (≥2 falls), injurious falls (requiring medical attention), unexplained falls, and syncope were reported at either Wave 2 or 3. Usual gait speed was the mean of two walks on a 4.88 m GAITRite walkway. Poisson regression analysis was used to examine associations between baseline antidepressant use and future falls adjusting for sociodemographics, physical, cognitive and mental health, and finally, gait speed. Compared to non-antidepressant users, those on antidepressants at baseline were more likely to report all types of falls (24.8-40.7% versus 9.8-18%) at follow-up. Antidepressants at baseline were independently associated with injurious falls (incidence risk ratio: 1.58, 95% confidence interval: 1.21, 2.06, z = 3.38, p = 0.001, df = 32) and unexplained falls (incidence risk ratio: 1.49, 95% confidence interval: 1.04, 2.15, z = 2.17, p = 0.030, df = 32) independent of all covariates including gait speed. There was little evidence to support the hypothesis that gait would (partly) explain any observed associations between baseline use of antidepressants and future falls. The underlying mechanisms of the observed relationships may be related to depression, vascular pathology, or direct effects of antidepressants. Clinicians should identify the best treatment option for an individual based on existing risk factors for outcomes such as falls.

P1854Clinical implications of physical function and resilience in patients undergoing transcatheter aortic valve implantation

Abstract Background Gait speed, as a measure of physical function and marker of frailty, is now routinely screened when evaluating patients with aortic stenosis (AS) for transcatheter aortic valve implantation (TAVI). Assessment of physical function is important to identify patients for whom TAVI may be futile and to assign patients to a procedural risk category. After TAVI, patients may exhibit physical resilience (improvement in physical function) or vulnerability (worsening). Characterizing the trajectory and clinical consequences of physical function after TAVI represent knowledge gaps in the field. Purpose Evaluate associations between physical resilience (improved gait speed) vs vulnerability (decline) after TAVI and subsequent death/hospitalization. Methods The REPRISE III trial compared a mechanically-expanded vs a self-expanding valve in 912 high/extreme risk patients with symptomatic AS. Patients (n=587) who underwent valve implantation and who had a gait speed recorded both pre- and 1-year post-TAVI were analyzed. Gait speed is based on the 5m walk test (slow: 5m in &gt;6s, &lt;0.83m/s; normal: ≥0.83m/s). Trajectory of physical function after TAVI was characterized in 2 ways. Model 1 examined 4 groups based on slow or normal gait speeds at baseline and 1-year post-TAVI. Model 2 examined gait speed change pre-TAVI to 1 year (adjusted for baseline gait speed). Using a landmark approach, the relationships between baseline and 1-year gait speed were evaluated in multivariable Cox PH models of outcomes between 1 and 2 years post-TAVI. Results A clinically-meaningful improvement (≥0.1m/s), no change (±0.1m/s), or decline (≥0.1/ms) in gait speed 1 year after TAVI was observed in 39%, 36%, and 26% of patients, respectively. Among the 4 groups defined by pre- and 1-year post-TAVI gait speeds, 1 to 2 year mortality or hospitalization rates were: 6.6% (normal/normal), 20.9% (normal/slow), 8.0% (slow/normal), and 21.5% (slow/slow). Adjusted hazard ratios of the 2 models are shown (Table). Table. Outcome by Change in Gait Speed Death/Hospitalization P-value Death P-value Hospitalization P-value Adjusted HR [95% CI] Adjusted HR [95% CI] Adjusted HR [95% CI] Model 1: Baseline/1 year Gait Speed (Normal/Normal (n=150) [referent]) Normal/Slow (n=59) 3.82 [1.61, 9.08] &lt;0.01 2.75 [0.96, 7.86] 0.06 7.31 [1.94, 27.58] &lt;0.01 Slow/Normal (n=114) 1.39 [0.53, 3.59] 0.50 1.44 [0.50, 4.12] 0.50 1.69 [0.38, 7.60] 0.49 Slow/Slow (n=253) 3.88 [1.91, 7.91] &lt;0.01 2.36 [1.02, 5.46] 0.045 3.89 [1.14, 13.27] 0.03 Model 2: Gait speed change Baseline to 1 year per 0.1m/s increase 0.83 [0.74, 0.92] &lt;0.01 0.92 [0.80, 1.04] 0.19 0.75 [0.64, 0.88] &lt;0.01 Conclusion These data reveal there is marked heterogeneity in the trajectory of physical function after TAVI and that this trajectory–more so than baseline physical function–is clinically consequential. Identifying and optimizing factors associated with physical resilience after TAVI may improve outcomes. Acknowledgement/Funding Boston Scientific

Short-Term Change in Gait Speed and Clinical Outcomes in Older Patients With Acute Heart Failure.

Evidence for the prognostic value of gait speed is largely based on a single measure at baseline, so we investigated the prognostic significance of change in gait speed in hospitalized older acute heart failure (AHF) patients.Methods and Results:This retrospective study was performed in a cohort of 388 AHF patients ≥60 years old (mean age: 74.8±7.8 years, 228 men). Routine geriatric assessment included gait speed measurement at baseline and at discharge. The primary outcome of this study was all-cause death. Gait speed increased from 0.74±0.25 m/s to 0.98±0.27 m/s after 13.5±11.0 days. Older age, shorter height and lower hemoglobin level at admission, prior HF admission, and higher baseline gait speed were independently associated with lesser improvement in gait speed. A total of 80 patients died and 137 patients were readmitted for HF over a mean follow-up period of 2.1±1.9 years. In multivariate analyses, change in gait speed showed inverse associations with all-cause death (hazard ratio [HR] per 0.1 m/s increase: 0.83; 95% confidence interval [CI]: 0.73 to 0.95; P=0.006) and with risk of readmission for HF (HR: 0.91; 95% CI: 0.83 to 0.99; P=0.036). Short-term improvement in gait speed during hospitalization was associated with reduced risks of death and readmission for HF in older patients with AHF.

Changes in knee extension peak torque and body composition and their relationship with change in gait speed

BackgroundSlow gait speed is a powerful predictor of disability in activities of daily living and mortality. Muscle strength and body composition change over time, but their changes differ by sex. How these parameters jointly affect gait speed decline is unknown. Understanding this association could help develop and evaluate the sex‐specific effects of lifestyle interventions to delay gait speed decline in older adults. We assessed whether changes in strength (Δstrength), appendicular lean mass (ΔALM), and fat mass (Δfat) jointly relate to change in gait speed and whether the association differs by sex.MethodsThe analytic sample comprised 575 women and 539 men aged 22–95 years enrolled in the Baltimore Longitudinal Study of Aging. Mean follow‐up was 4.0 years. Measures included isometric knee extension strength, dual‐energy X‐ray absorptiometry‐assessed ALM and fat mass, and gait speed from the 400 m fast pace walk. Sex‐specific linear mixed models were adjusted for follow‐up time and baseline age, race, height, ALM, fat mass, peak torque, and gait speed. We also included second‐order interaction terms of the key predictive variables (e.g. Δstrength × ΔALM). To interpret the interactions, we estimated average gait declines using the 25th or 75th percentile of the two significant predictive variables and then assessed which condition relates to larger decline in gait speed.ResultsIn both sexes, independent of ΔALM and Δfat, larger decline in strength significantly related to larger decline in gait speed (P = 0.01 for both sexes). In men, interactions between Δstrength × ΔALM and Δfat by ΔALM were associated with change in gait speed; men with greater declines in both muscle strength and ALM or greater declines in both ALM and fat have steeper gait speed decline. In contrast, in women, the interaction between Δfat and ΔALM was associated with change in gait speed; women with an increase in fat mass combined with less decline in ALM have steeper gait speed decline.ConclusionsWhile change in strength affects change in gait speed in both sexes, the effects of body composition change differ by sex. Dual‐energy X‐ray absorptiometry‐based estimates of lean mass may be confounded by intramuscular fat. Future studies should examine sex‐specific combined effects of change in strength and body composition on mobility using multiple techniques to measure body composition. Intervention studies should consider testing sex‐specific interventions on body composition.