Association of fatigue, inflammation, and physical activity on gait speed: the Long Life Family Study

Abstract Background Gait speed is a powerful indicator of health with aging. Potential genetic contributions to gait speed and its decline with aging are not well defined. We determined the heritability of and potential genetic regions underlying change in gait speed using longitudinal data from 2379 individuals belonging to 509 families in the Long Life Family Study (mean age 64±12, range 30–110 years; 45% men). Methods Gait-speed was measured over 4 meters at baseline and follow up (7±1 years). Quantitative trait linkage analyses were completed using pedigree-based maximum-likelihood methods with logarithm of the odds (LOD) scores >3.0 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. Results At baseline, 26.9% of individuals had “slow” 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 (h 2 = 0.24-0.32, p<0.05). We did not find significant evidence for linkage for baseline gait speed; however, we identified a significant 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). Association analyses on chromosome 16 showed that the strongest variant resides within the ADCY9 gene. Conclusion Further analysis of the chromosome 16 region, and ADCY9 gene, may yield new insight on the biology of mobility decline with aging.

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PERCEIVED PHYSICAL FATIGABILITY PREDICTS ALL-CAUSE MORTALITY: THE LONG LIFE FAMILY STUDY

Innovation in Aging ◽

10.1093/geroni/igz038.3272 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S895-S895

Author(s):

Nancy W Glynn ◽

Theresa Gmelin ◽

Sharon W Renner ◽

Robert M Boudreau ◽

Mary Feitosa ◽

...

Keyword(s):

Physical Activity ◽

Family Study ◽

Activity Index ◽

Self Report ◽

Clinical Tool ◽

Risk Of Mortality ◽

All Cause Mortality ◽

Long Life ◽

And Function

Abstract Fatigability, the likelihood of fatigue with lower versus higher levels of exertion, is associated with declines in physical function and disability and related to fitness. Thus, fatigability may be a good predictor of mortality. We examined this relationship in the Long Life Family Study (LLFS), an international family cohort enriched for longevity and their spousal controls. We measured perceived physical fatigability at Visit 2 (2014-2017) using the Pittsburgh Fatigability Scale (PFS, 0-50 with higher score=greater fatigability). We identified deaths by family members notifying field centers, reporting during annual phone follow-up, or finding an obituary when unable to reach. Otherwise, we censored participants at most recent contact date when confirmed alive. Covariates included age, sex, and self-reported physical activity using the Framingham Physical Activity Index. We adjusted all analyses for field center and family structure. Participants alive ≥60 years (range 60-108, mean 73.6±10.5) and completed the PFS (N=2,326) at Visit 2 were predominantly white (99.5%) and female (55.1%). Post-Visit 2, 195 (8.4%) died during mean 2.5±1.0 years of follow-up. Age-adjusted PFS score was 7.7 points greater (p<.0001) for those who died (19.8) compared to alive (12.1). Using Cox Proportional-Hazard modeling, each 5-point greater PFS score was associated with 31% (HR: 1.31, 95% CI 1.18,1.43) higher all-cause mortality rate adjusted for covariates listed above. Further adjustment for comorbidities did not attenuate association. PFS’s perceived physical fatigability score may be a useful self-report clinical tool to predict higher risk of mortality among older adults when objective measures of fitness and function are unavailable.

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

Innovation in Aging ◽

10.1093/geroni/igaa057.804 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 249-250

Author(s):

Adam Santanasto ◽

Ryan Cvejkus ◽

Mary Wojczynski ◽

Nicole Schupf ◽

Megan Marron ◽

...

Keyword(s):

Physical Function ◽

Grip Strength ◽

Gait Speed ◽

Family Study ◽

Future Research ◽

Enzyme Linked Immunosorbent Assay ◽

Type Iii ◽

Procollagen Type ◽

Long Life ◽

Chair Rise

Abstract 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.

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

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa197 ◽

2020 ◽

Author(s):

Adam J Santanasto ◽

Ryan K Cvejkus ◽

Mary K Wojczynski ◽

Megan M Marron ◽

Nicole Schupf ◽

...

Keyword(s):

Physical Function ◽

Grip Strength ◽

Gait Speed ◽

Family Study ◽

Future Research ◽

Enzyme Linked Immunosorbent Assay ◽

Type Iii ◽

Procollagen Type ◽

Long Life ◽

Chair Rise

Abstract Background 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. Method 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. Results 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. Conclusion 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.

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The Benefits of Physical Activity in Individuals with Cardiovascular Risk Factors: A Longitudinal Investigation Using fNIRS and Dual-Task Walking

Journal of Clinical Medicine ◽

10.3390/jcm10040579 ◽

2021 ◽

Vol 10 (4) ◽

pp. 579

Author(s):

Deborah Talamonti ◽

Thomas Vincent ◽

Sarah Fraser ◽

Anil Nigam ◽

Frédéric Lesage ◽

...

Keyword(s):

Physical Activity ◽

Risk Factors ◽

Older Adults ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Cognitive Performance ◽

Dual Task ◽

Gait Speed ◽

Regular Physical Activity ◽

Cortical Response

Cardiovascular fitness is linked to better executive functions, preserved gait speed, and efficient cortical activity. Older adults with cardiovascular risk factors (CVRFs) typically show poor cognitive performance, low physical fitness, and altered brain functioning compared with healthy individuals. In the current study, the impact of regular physical activity on cognition, locomotion, and brain functions was explored in a cohort of older adults with low or high CVRFs. Cortical activation of the frontal areas was investigated using functional Near-Infrared Spectroscopy (fNIRS) at baseline, at 6 months and at 12 months. Evoked cortical response and behavioral performance were assessed using the dual-task walking paradigm, consisting of three conditions: single cognitive task (2-back task), single walking task (walking), and dual-task (2-back whilst walking). Results show greater task-related cortical response at baseline in individuals with high CVRFs compared to those with low CVRFs. Moreover, participants with high CVRFs benefitted the most from participating in regular physical activity, as their cortical response decreased at the 12-month follow-up and became comparable to that of participants with low CVRFs. These changes were observed in conjunction with improved cognitive performance and stable gait speed throughout the 12-month period in both groups. Our findings provide evidence that participation in regular physical activity may be especially beneficial in individuals with CVRFs by promoting brain and cognitive health, thus potentially contributing to prevention of cognitive decline. Future research may explore whether such effects are maintained in the long-term in order to design ad-hoc interventions in this specific population.

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Novel Analytic Approaches to Investigate Minute-Level Actigraphy and Associations With Physical Function

Innovation in Aging ◽

10.1093/geroni/igaa057.630 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 194-195

Author(s):

Kaiyuan Hua ◽

Sheng Luo ◽

Katherine Hall ◽

Miriam Morey ◽

Harvey Cohen

Keyword(s):

Physical Activity ◽

Data Analysis ◽

Physical Function ◽

Functional Data Analysis ◽

Functional Data ◽

Gait Speed ◽

Community Dwelling ◽

Accelerometer Data ◽

Single Leg Stance ◽

Minute Walk

Abstract Background. Functional decline in conjunction with low levels of physical activity has implications for health risks in older adults. Previous studies have examined the associations between accelerometry-derived activity and physical function, but most of these studies reduced these data into average means of total daily physical activity (e.g., daily step counts). A new method of analysis “functional data analysis” provides more in-depth capability using minute-level accelerometer data. Methods. A secondary analysis of community-dwelling adults ages 30 to 90+ residing in southwest region of North Carolina from the Physical Performance across the Lifespan (PALS) study. PALS assessments were completed in-person at baseline and one-week of accelerometry. Final analysis includes 669 observations at baseline with minute-level accelerometer data from 7:00 to 23:00, after removing non-wear time. A novel scalar-on-function regression analysis was used to explore the associations between baseline physical activity features (minute-by-minute vector magnitude generated from accelerometer) and baseline physical function (gait speed, single leg stance, chair stands, and 6-minute walk test) with control for baseline age, sex, race and body mass index. Results. The functional regressions were significant for specific times of day indicating increased physical activity associated with increased physical function around 8:00, 9:30 and 15:30-17:00 for rapid gait speed; 9:00-10:30 and 15:00-16:30 for normal gait speed; 9:00-10:30 for single leg stance; 9:30-11:30 and 15:00-18:00 for chair stands; 9:00-11:30 and 15:00-18:30 for 6-minute walk. Conclusion. This method of functional data analysis provides news insights into the relationship between minute-by-minute daily activity and health.

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INTEGRATIVE ANALYSIS OF LONGITUDINAL CHANGES OF NEUROPSYCHOLOGICAL TESTS IN LONG LIFE FAMILY STUDY PARTICIPANTS

Innovation in Aging ◽

10.1093/geroni/igy023.1510 ◽

2018 ◽

Vol 2 (suppl_1) ◽

pp. 404-405

Author(s):

P Sebastiani ◽

S L Andersen ◽

B Sweigart ◽

S Cosentino ◽

B Thyragajan ◽

...

Keyword(s):

Neuropsychological Tests ◽

Family Study ◽

Integrative Analysis ◽

Longitudinal Changes ◽

Long Life ◽

Study Participants

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Physical Activity Trajectories and Associated Changes in Physical Performance in Older Men: The MrOS Study

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa073 ◽

2020 ◽

Vol 75 (10) ◽

pp. 1967-1973

Author(s):

Deepika R Laddu ◽

Neeta Parimi ◽

Katie L Stone ◽

Jodi Lapidus ◽

Andrew R Hoffman ◽

...

Keyword(s):

Physical Activity ◽

Grip Strength ◽

High Activity ◽

Physical Performance ◽

Gait Speed ◽

Functional Independence ◽

Performance Measure ◽

Least Square ◽

Activity Group ◽

Low Activity

Abstract Background Physical activity (PA) is important to maintaining functional independence. It is not clear how patterns of change in late-life PA are associated with contemporaneous changes in physical performance measures. Methods Self-reported PA, gait speed, grip strength, timed chair stand, and leg power were assessed in 3,865 men aged ≥ 65 years at baseline (2000–2002) and Year 7 (2007–2009). Group-based trajectory modeling, using up to four PA measures over this period, identified PA trajectories. Multivariate linear regression models (adjusted least square mean [95% confidence interval {CI}]) described associations between-PA trajectories and concurrent changes in performance. Results Three discrete PA patterns were identified, all with declining PA. Linear declines in each performance measure (baseline to Year 7) were observed across all three PA groups, but there was some variability in the rate of decline. Multivariate models assessing the graded response by PA trajectory showed a trend where the high-activity group had the smallest declines in performance while the low-activity group had the largest (p-for trend < .03). Changes in the high-activity group were the following: gait speed (−0.10 m/s [−0.12, −0.08]), grip strength (−3.79 kg [−4.35, −3.23]), and chair stands (−0.38 [−0.50, −0.25]), whereas changes in the low-activity group were the following: gait speed (−0.16 [−0.17, −0.14]), grip strength (−4.83 kg [−5.10, −4.55]), and chair stands (−0.53 [−0.59, −0.46]). Between-group differences in leg power trajectories across PA patterns were not significant. Conclusions Declines in functional performance were higher among those with lower PA trajectories, providing further evidence for the interrelationship between changes in PA and performance during old age.

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