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1.  Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: individual participant meta-analysis 
Wormser, David | Angelantonio, Emanuele Di | Kaptoge, Stephen | Wood, Angela M | Gao, Pei | Sun, Qi | Walldius, Göran | Selmer, Randi | Verschuren, WM Monique | Bueno-de-Mesquita, H Bas | Engström, Gunnar | Ridker, Paul M | Njølstad, Inger | Iso, Hiroyasu | Holme, Ingar | Giampaoli, Simona | Tunstall-Pedoe, Hugh | Gaziano, J Michael | Brunner, Eric | Kee, Frank | Tosetto, Alberto | Meisinger, Christa | Brenner, Hermann | Ducimetiere, Pierre | Whincup, Peter H | Tipping, Robert W | Ford, Ian | Cremer, Peter | Hofman, Albert | Wilhelmsen, Lars | Clarke, Robert | de Boer, Ian H | Jukema, J Wouter | Ibañez, Alejandro Marín | Lawlor, Debbie A | D'Agostino, Ralph B | Rodriguez, Beatriz | Casiglia, Edoardo | Stehouwer, Coen DA | Simons, Leon A | Nietert, Paul J | Barrett-Connor, Elizabeth | Panagiotakos, Demosthenes B | Björkelund, Cecilia | Strandberg, Timo E | Wassertheil-Smoller, Sylvia | Blazer, Dan G | Meade, Tom W | Welin, Lennart | Svärdsudd, Kurt | Woodward, Mark | Nissinen, Aulikki | Kromhout, Daan | Jørgensen, Torben | Tilvis, Reijo S | Guralnik, Jack M | Rosengren, Annika | Taylor, James O | Kiechl, Stefan | Dagenais, Gilles R | Gerry, F | Fowkes, R | Wallace, Robert B | Khaw, Kay-Tee | Shaffer, Jonathan A | Visser, Marjolein | Kauhanen, Jussi | Salonen, Jukka T | Gallacher, John | Ben-Shlomo, Yoav | Kitamura, Akihiko | Sundström, Johan | Wennberg, Patrik | Kiyohara, Yutaka | Daimon, Makoto | de la Cámara, Agustin Gómez | Cooper, Jackie A | Onat, Altan | Devereux, Richard | Mukamal, Kenneth J | Dankner, Rachel | Knuiman, Matthew W | Crespo, Carlos J | Gansevoort, Ron T | Goldbourt, Uri | Nordestgaard, Børge G | Shaw, Jonathan E | Mussolino, Michael | Nakagawa, Hidaeki | Fletcher, Astrid | Kuller, Lewis H | Gillum, Richard F | Gudnason, Vilmundur | Assmann, Gerd | Wald, Nicholas | Jousilahti, Pekka R | Greenland, Philip | Trevisan, Maurizio | Ulmer, Hanno | Butterworth, Adam S | Folsom, Aaron R | Davey-Smith, George | Hu, Frank B | Danesh, John | Tipping, Robert W | Ford, Charles E | Simpson, Lara M | Walldius, Göran | Jungner, Ingmar | Folsom, Aaron R | Demerath, Ellen W | Franceschini, Nora | Lutsey, Pamela L | Panagiotakos, Demosthenes B | Pitsavos, Christos | Chrysohoou, Christina | Stefanadis, Christodoulos | Shaw, Jonathan E | Atkins, Robert | Zimmet, Paul Z | Barr, Elizabeth LM | Knuiman, Matthew W | Whincup, Peter H | Wannamethee, S Goya | Morris, Richard W | Willeit, Johann | Kiechl, Stefan | Weger, Siegfried | Oberhollenzer, Friedrich | Wald, Nicholas | Ebrahim, Shah | Lawlor, Debbie A | Gallacher, John | Ben-Shlomo, Yoav | Yarnell, John WG | Casiglia, Edoardo | Tikhonoff, Valérie | Greenland, Philip | Shay, Christina M | Garside, Daniel B | Nietert, Paul J | Sutherland, Susan E | Bachman, David L | Keil, Julian E | de Boer, Ian H | Kizer, Jorge R | Psaty, Bruce M | Mukamal, Kenneth J | Nordestgaard, Børge G | Tybjærg-Hansen, Anne | Jensen, Gorm B | Schnohr, Peter | Giampaoli, Simona | Palmieri, Luigi | Panico, Salvatore | Pilotto, Lorenza | Vanuzzo, Diego | de la Cámara, Agustin Gómez | Simons, Leon A | Simons, Judith | McCallum, John | Friedlander, Yechiel | Gerry, F | Fowkes, R | Price, Jackie F | Lee, Amanda J | Taylor, James O | Guralnik, Jack M | Phillips, Caroline L | Wallace, Robert B | Kohout, Frank J | Cornoni-Huntley, Joan C | Guralnik, Jack M | Blazer, Dan G | Guralnik, Jack M | Phillips, Caroline L | Phillips, Caroline L | Guralnik, Jack M | Khaw, Kay-Tee | Wareham, Nicholas J | Brenner, Hermann | Schöttker, Ben | Müller, Heiko | Rothenbacher, Dietrich | Wennberg, Patrik | Jansson, Jan-Håkan | Nissinen, Aulikki | Donfrancesco, Chiara | Giampaoli, Simona | Woodward, Mark | Vartiainen, Erkki | Jousilahti, Pekka R | Harald, Kennet | Salomaa, Veikko | D'Agostino, Ralph B | Vasan, Ramachandran S | Fox, Caroline S | Pencina, Michael J | Daimon, Makoto | Oizumi, Toshihide | Kayama, Takamasa | Kato, Takeo | Bladbjerg, Else-Marie | Jørgensen, Torben | Møller, Lars | Jespersen, Jørgen | Dankner, Rachel | Chetrit, Angela | Lubin, Flora | Svärdsudd, Kurt | Eriksson, Henry | Welin, Lennart | Lappas, Georgios | Rosengren, Annika | Lappas, Georgios | Welin, Lennart | Svärdsudd, Kurt | Eriksson, Henry | Lappas, Georgios | Bengtsson, Calle | Lissner, Lauren | Björkelund, Cecilia | Cremer, Peter | Nagel, Dorothea | Strandberg, Timo E | Salomaa, Veikko | Tilvis, Reijo S | Miettinen, Tatu A | Tilvis, Reijo S | Strandberg, Timo E | Kiyohara, Yutaka | Arima, Hisatomi | Doi, Yasufumi | Ninomiya, Toshiharu | Rodriguez, Beatriz | Dekker, Jacqueline M | Nijpels, Giel | Stehouwer, Coen DA | Hu, Frank B | Sun, Qi | Rimm, Eric B | Willett, Walter C | Iso, Hiroyasu | Kitamura, Akihiko | Yamagishi, Kazumasa | Noda, Hiroyuki | Goldbourt, Uri | Vartiainen, Erkki | Jousilahti, Pekka R | Harald, Kennet | Salomaa, Veikko | Kauhanen, Jussi | Salonen, Jukka T | Kurl, Sudhir | Tuomainen, Tomi-Pekka | Poppelaars, Jan L | Deeg, Dorly JH | Visser, Marjolein | Meade, Tom W | De Stavola, Bianca Lucia | Hedblad, Bo | Nilsson, Peter | Engström, Gunnar | Verschuren, WM Monique | Blokstra, Anneke | de Boer, Ian H | Shea, Steven J | Meisinger, Christa | Thorand, Barbara | Koenig, Wolfgang | Döring, Angela | Verschuren, WM Monique | Blokstra, Anneke | Bueno-de-Mesquita, H Bas | Wilhelmsen, Lars | Rosengren, Annika | Lappas, Georgios | Fletcher, Astrid | Nitsch, Dorothea | Kuller, Lewis H | Grandits, Greg | Tverdal, Aage | Selmer, Randi | Nystad, Wenche | Mussolino, Michael | Gillum, Richard F | Hu, Frank B | Sun, Qi | Manson, JoAnn E | Rimm, Eric B | Hankinson, Susan E | Meade, Tom W | De Stavola, Bianca Lucia | Cooper, Jackie A | Bauer, Kenneth A | Davidson, Karina W | Kirkland, Susan | Shaffer, Jonathan A | Shimbo, Daichi | Kitamura, Akihiko | Iso, Hiroyasu | Sato, Shinichi | Holme, Ingar | Selmer, Randi | Tverdal, Aage | Nystad, Wenche | Nakagawa, Hidaeki | Miura, Katsuyuki | Sakurai, Masaru | Ducimetiere, Pierre | Jouven, Xavier | Bakker, Stephan JL | Gansevoort, Ron T | van der Harst, Pim | Hillege, Hans L | Crespo, Carlos J | Garcia-Palmieri, Mario R | Kee, Frank | Amouyel, Philippe | Arveiler, Dominique | Ferrières, Jean | Schulte, Helmut | Assmann, Gerd | Jukema, J Wouter | de Craen, Anton JM | Sattar, Naveed | Stott, David J | Cantin, Bernard | Lamarche, Benoît | Després, Jean-Pierre | Dagenais, Gilles R | Barrett-Connor, Elizabeth | Bergstrom, Jaclyn | Bettencourt, Richele R | Buisson, Catherine | Gudnason, Vilmundur | Aspelund, Thor | Sigurdsson, Gunnar | Thorsson, Bolli | Trevisan, Maurizio | Hofman, Albert | Ikram, M Arfan | Tiemeier, Henning | Witteman, Jacqueline CM | Tunstall-Pedoe, Hugh | Tavendale, Roger | Lowe, Gordon DO | Woodward, Mark | Devereux, Richard | Yeh, Jeun-Liang | Ali, Tauqeer | Calhoun, Darren | Ben-Shlomo, Yoav | Davey-Smith, George | Onat, Altan | Can, Günay | Nakagawa, Hidaeki | Sakurai, Masaru | Nakamura, Koshi | Morikawa, Yuko | Njølstad, Inger | Mathiesen, Ellisiv B | Løchen, Maja-Lisa | Wilsgaard, Tom | Sundström, Johan | Ingelsson, Erik | Michaëlsson, Karl | Cederholm, Tommy | Gaziano, J Michael | Buring, Julie | Ridker, Paul M | Gaziano, J Michael | Ridker, Paul M | Ulmer, Hanno | Diem, Günter | Concin, Hans | Rodeghiero, Francesco | Tosetto, Alberto | Wassertheil-Smoller, Sylvia | Manson, JoAnn E | Marmot, Michael | Clarke, Robert | Fletcher, Astrid | Brunner, Eric | Shipley, Martin | Kivimaki, Mika | Ridker, Paul M | Buring, Julie | Ford, Ian | Robertson, Michele | Ibañez, Alejandro Marín | Feskens, Edith | Geleijnse, Johanna M | Kromhout, Daan | Walker, Matthew | Watson, Sarah | Alexander, Myriam | Butterworth, Adam S | Angelantonio, Emanuele Di | Franco, Oscar H | Gao, Pei | Gobin, Reeta | Haycock, Philip | Kaptoge, Stephen | Seshasai, Sreenivasa R Kondapally | Lewington, Sarah | Pennells, Lisa | Rapsomaniki, Eleni | Sarwar, Nadeem | Thompson, Alexander | Thompson, Simon G | Walker, Matthew | Watson, Sarah | White, Ian R | Wood, Angela M | Wormser, David | Zhao, Xiaohui | Danesh, John
Background The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.
Methods We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual–participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.
Results For people born between 1900 and 1960, mean adult height increased 0.5–1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96–0.99) for death from any cause, 0.94 (0.93–0.96) for death from vascular causes, 1.04 (1.03–1.06) for death from cancer and 0.92 (0.90–0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12–1.42) for risk of melanoma death to 0.84 (0.80–0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.
Conclusion Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
doi:10.1093/ije/dys086
PMCID: PMC3465767  PMID: 22825588
Height; cardiovascular disease; cancer; cause-specific mortality; epidemiological study; meta-analysis
2.  Motoric cognitive risk syndrome 
Neurology  2014;83(8):718-726.
Objectives:
Our objective is to report prevalence of motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints, in multiple countries, and its association with dementia risk.
Methods:
Pooled MCR prevalence analysis of individual data from 26,802 adults without dementia and disability aged 60 years and older from 22 cohorts from 17 countries. We also examined risk of incident cognitive impairment (Mini-Mental State Examination decline ≥4 points) and dementia associated with MCR in 4,812 individuals without dementia with baseline Mini-Mental State Examination scores ≥25 from 4 prospective cohort studies using Cox models adjusted for potential confounders.
Results:
At baseline, 2,808 of the 26,802 participants met MCR criteria. Pooled MCR prevalence was 9.7% (95% confidence interval [CI] 8.2%–11.2%). MCR prevalence was higher with older age but there were no sex differences. MCR predicted risk of developing incident cognitive impairment in the pooled sample (adjusted hazard ratio [aHR] 2.0, 95% CI 1.7–2.4); aHRs were 1.5 to 2.7 in the individual cohorts. MCR also predicted dementia in the pooled sample (aHR 1.9, 95% CI 1.5–2.3). The results persisted even after excluding participants with possible cognitive impairment, accounting for early dementia, and diagnostic overlap with other predementia syndromes.
Conclusion:
MCR is common in older adults, and is a strong and early risk factor for cognitive decline. This clinical approach can be easily applied to identify high-risk seniors in a wide variety of settings.
doi:10.1212/WNL.0000000000000717
PMCID: PMC4150127  PMID: 25031288
3.  What Physical Attributes Underlie Self-Reported vs. Observed Ability to Walk 400 m in Later Life? 
Objective
The aims of this study were to evaluate and contrast the physical attributes that are associated with self-reported vs. observed ability to walk 400 m among older adults.
Design
Analysis of baseline and 3-yr data from 1026 participants 65 yrs or older in the InCHIANTI (Invecchiare in Chianti) study was conducted. Observed and self-reported ability to walk 400 m at baseline and at 3 yrs were primary outcomes. Predictors included leg speed, leg strength, leg strength symmetry, range of motion, balance, and kyphosis.
Results
Balance, leg speed, leg strength, kyphosis, leg strength symmetry, and knee range of motion were associated with self-reported ability to walk 400 m at baseline (P < 0.001, c = 0.85). Balance, leg speed, and knee range of motion were associated with observed 400-m walk (P < 0.001, c = 0.85) at baseline. Prospectively, baseline leg speed and leg strength were predictive of both self-reported (P < 0.001, c = 0.79) and observed (P < 0.001, c = 0.72) ability to walk 400 m at 3 yrs.
Conclusions
The profiles of attributes that are associated with self-reported vs. observed walking ability differ. The factor most consistently associated with current and future walking ability is leg speed. These results draw attention to important foci for rehabilitation.
doi:10.1097/PHM.0000000000000034
PMCID: PMC4304676  PMID: 24322434
Physical Performance; Rehabilitation; Successful Aging; Mobility Limitation
4.  Sensorimotor and psychosocial determinants of 3-year incident mobility disability in middle-aged and older adults 
Age and Ageing  2014;43(1):64-69.
Objective: to identify sensorimotor and psychosocial determinants of 3-year incident mobility disability.
Design: prospective.
Setting: population-based sample of community-dwelling older persons.
Participants: community-living middle-aged and older persons (age: 50–85 years) without baseline mobility disability (n = 622).
Measurements: mobility disability, defined as self-reported inability to walk a quarter mile without resting or inability to walk up a flight of stairs unsupported, was ascertained at baseline and 3-year follow-up. Potential baseline determinant characteristics included demographics, education, social support, financial condition, knee extensor strength, visual contrast sensitivity, cognition, depression, presence of chronic conditions and history of falls.
Results: a total of 13.5% participant reported 3-year incident mobility disability. Age ≥75 years, female sex, knee extensor strength in the lowest quartile, visual contrast sensitivity <1.7 on the Pelli-Robson chart or significant depressive symptoms (CESD score >16) were independent determinants of 3-year incident mobility disability (ORs 1.84–16.51).
Conclusions: low visual contrast sensitivity, poor knee extensor strength and significant depressive symptoms are independent determinants of future onset of mobility disability.
doi:10.1093/ageing/aft135
PMCID: PMC3861339  PMID: 24042004
mobility; disability; depression; vision; muscle strength; older people
5.  Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE Study randomized clinical trial 
JAMA  2014;311(23):2387-2396.
SUMMARY
Importance
In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining if physical activity prevents or delays mobility disability.
Objective
To test the hypothesis that a long-term structured physical activity program is more effective than a health education program (also referred to as a successful aging program) in reducing the risk of major mobility disability.
Design, Setting, and Participants
The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial that enrolled participants between February 2010 and December 2011, who participated for an average of 2.6 years. Follow-up ended in December 2013. Outcome assessors were blinded to the intervention assignment. Participants were recruited from urban, suburban and rural communities at 8 field centers throughout the US. We randomized a volunteer sample of 1,635 sedentary men and women aged 70–89 years who had physical limitations, defined as a score on the Short Physical Performance Battery of 9 or below, but were able to walk 400 m.
Interventions
Participants were randomized to a structured moderate intensity physical activity program (n=818) done in a center and at home that included including aerobic, resistance and flexibility training activities or to a health education program (n=817) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises.
Main Outcomes and Measures
The primary outcome was major mobility disability objectively defined by loss of ability to walk 400 m.
Results
Incident major mobility disability occurred in 30.1% (n=246/818) of physical activity and 35.5% (n=290/817) of health education participants (HR=0.82, 95%CI=0.69–0.98, p=0.03). Persistent mobility disability was experienced by 120/818 (14.7%) physical activity and 162/817 (19.8%) health education participants (HR=0.72; 95%CI=0.57–0.91; p=0.006). Serious adverse events were reported by 404/818 (49.4%) of the physical activity and 373/817 (45.7%) of the health education participants (Risk Ratio=1.08; 95%CI=0.98–1.20).
Conclusions and Relevance
A structured moderate intensity physical activity program, compared with a health education program, reduced major mobility disability over 2.6 years among older adults at risk of disability. These findings suggest mobility benefit from such a program in vulnerable older adults.
Registration
ClinicalsTrials.gov identifier NCT01072500.
doi:10.1001/jama.2014.5616
PMCID: PMC4266388  PMID: 24866862
6.  Lifestyle Interventions and Independence for Elders Study: Recruitment and Baseline Characteristics 
Background.
Recruitment of older adults into long-term clinical trials involving behavioral interventions is a significant challenge. The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase 3 multicenter randomized controlled multisite trial, designed to compare the effects of a moderate-intensity physical activity program with a successful aging health education program on the incidence of major mobility disability (the inability to walk 400 m) in sedentary adults aged 70–89 years, who were at high risk for mobility disability (scoring ≤9 on the Short Physical Performance Battery) at baseline.
Methods.
Recruitment methods, yields, efficiency, and costs are described together with a summary of participant baseline characteristics. Yields were examined across levels of sex, race and ethnicity, and Short Physical Performance Battery, as well as by site.
Results.
The 21-month recruiting period resulted in 14,812 telephone screens; 1,635 participants were randomized (67.2% women, 21.0% minorities, 44.7% with Short Physical Performance Battery scores ≤7). Of the telephone-screened participants, 37.6% were excluded primarily because of regular participation in physical activity, health exclusions, or self-reported mobility disability. Direct mailing was the most productive recruitment strategy (59.5% of randomized participants). Recruitment costs were $840 per randomized participant. Yields differed by sex and Short Physical Performance Battery. We accrued 11% more participant follow-up time than expected during the recruitment period as a result of the accelerated recruitment rate.
Conclusions.
The LIFE Study achieved all recruitment benchmarks. Bulk mailing is an efficient method for recruiting high-risk community-dwelling older persons (including minorities), from diverse geographic areas for this long-term behavioral trial.
doi:10.1093/gerona/glt064
PMCID: PMC3814232  PMID: 23716501
Mobile disability; Older adults; Physical activity; Minority recruitment; Randomized controlled trial.
7.  The MAT-sf: Clinical Relevance and Validity 
Background.
The measurement of mobility is essential to both aging research and clinical practice. A newly developed self-report measure of mobility, the mobility assessment tool—short form (MAT-sf), uses video animations to improve measurement accuracy/precision. Using a large baseline data set, we recalibrated the items, evaluated the extent to which older patients’ self-efficacy (i.e., confidence) for walking was related to MAT-sf scores beyond their actual 400-m walk time, and assessed the relationship of the MAT-sf with body mass index and other clinical variables.
Methods.
The analyses employed baseline data from the Lifestyle Interventions and Independence for Elders Study.
Results.
Item recalibration demonstrated that the MAT-sf scoring algorithm was robust. In an analysis with 400-m walk time and self-efficacy regressed on the MAT-sf, both variables shared unique variance with the MAT-sf (p < .001). The MAT-sf was inversely related to several comorbidities, most notably hypertension and arthritis (p < .001), and scores were lowest when body mass index ≥ 35kg/m2. Finally, MAT-sf scores were directly related to Short Physical Performance Battery scores, inversely related to difficulty with activities of daily living (p < .001) and higher for men than for women (p < .001).
Conclusions.
The findings extend the validity and clinical utility of this innovative tool for assessing self-reported mobility in older adults. Longitudinal data on the MAT-sf from the Lifestyle Interventions and Independence for Elders Study will enable us to evaluate the relative contributions of self-report and performance-based measures of mobility on important health outcomes.
doi:10.1093/gerona/glt068
PMCID: PMC3814234  PMID: 23685766
Mobility; Geriatric assessment; Physical function; MAT-sf
8.  Prevalence and Impact of Pain among Older Adults in the United States: Findings from the 2011 National Health and Aging Trends Study 
Pain  2013;154(12):10.1016/j.pain.2013.07.029.
The study sought to determine the prevalence and impact of pain in a nationally representative sample of older adults in the United States (US). Data from the 2011 National Health and Aging Trends Study were analyzed. In-person interviews were conducted in 7,601 adults ages ≥65 years. The response rate was 71.0% and all analyses were weighted to account for the sampling design. The overall prevalence of bothersome pain in the last month was 52.9%, afflicting 18.7 million older adults in the US. Pain did not vary across age groups (P=0.21) and this pattern remained unchanged when accounting for cognitive performance, dementia, proxy-responses, and residential care living status. Pain prevalence was higher in women and in older adults with obesity, musculoskeletal conditions, and depressive symptoms (P<0.001). The majority (74.9%) of older adults with pain endorsed multiple sites of pain. Several measures of physical capacity, including grip strength and lower extremity physical performance, were associated with pain and multisite pain. For example, self-reported inability to walk 3 blocks was 72% higher in participants with than without pain [adjusted Prevalence Ratio=1.72 (95% Confidence Interval: 1.56–1.90)]. Participants with 1, 2, 3, and >4 sites of pain had gait speeds that were 0.01, 0.03, 0.05, and 0.08 meters per second slower, respectively, than older adults without pain, adjusting for disease burden and other confounders (P<0.001). In summary, bothersome pain in the last month was reported by half of the older adult population of the US in 2011 and was strongly associated with decreased physical function.
doi:10.1016/j.pain.2013.07.029
PMCID: PMC3843850  PMID: 24287107
pain; aging; geriatric assessment; locomotor activity; prevalence study
9.  Aging, the Central Nervous System, and Mobility 
Background.
Mobility limitations are common and hazardous in community-dwelling older adults but are largely understudied, particularly regarding the role of the central nervous system (CNS). This has limited development of clearly defined pathophysiology, clinical terminology, and effective treatments. Understanding how changes in the CNS contribute to mobility limitations has the potential to inform future intervention studies.
Methods.
A conference series was launched at the 2012 conference of the Gerontological Society of America in collaboration with the National Institute on Aging and the University of Pittsburgh. The overarching goal of the conference series is to facilitate the translation of research results into interventions that improve mobility for older adults.
Results.
Evidence from basic, clinical, and epidemiological studies supports the CNS as an important contributor to mobility limitations in older adults without overt neurologic disease. Three main goals for future work that emerged were as follows: (a) develop models of mobility limitations in older adults that differentiate aging from disease-related processes and that fully integrate CNS with musculoskeletal contributors; (b) quantify the contribution of the CNS to mobility loss in older adults in the absence of overt neurologic diseases; (c) promote cross-disciplinary collaboration to generate new ideas and address current methodological issues and barriers, including real-world mobility measures and life-course approaches.
Conclusions.
In addition to greater cross-disciplinary research, there is a need for new approaches to training clinicians and investigators, which integrate concepts and methodologies from individual disciplines, focus on emerging methodologies, and prepare investigators to assess complex, multisystem associations.
doi:10.1093/gerona/glt089
PMCID: PMC3805295  PMID: 23843270
Motor control; Central nervous system; Mobility.
10.  PROGENITOR CELL RELEASE PLUS EXERCISE TO IMPROVE FUNCTIONAL PERFORMANCE IN PERIPHERAL ARTERY DISEASE: THE PROPEL STUDY 
Contemporary clinical trials  2013;36(2):502-509.
Functional impairment, functional decline, and mobility loss are major public health problems in people with lower extremity peripheral artery disease (PAD). Few medical therapies significantly improve walking performance in PAD. We describe methods for the PROgenitor cell release Plus Exercise to improve functionaL performance in PAD (PROPEL) Study, a randomized controlled clinical trial designed to determine whether granulocyte-macrophage colony stimulating factor (GM-CSF) combined with supervised treadmill walking exercise improves six-minute walk distance more than GM-CSF alone, more than supervised treadmill exercise alone, and more than placebo plus attention control in participants with PAD, respectively. PROPEL Study participants are randomized to one of four arms in a 2 by 2 factorial design. The four study arms are GM-CSF plus supervised treadmill exercise, GM-CSF plus attention control, placebo plus supervised exercise therapy, or placebo plus attention control. The primary outcome is change in six-minute walk distance at 12-week follow-up. Secondary outcomes include change in brachial artery flow-mediated dilation (FMD), change in maximal treadmill walking time, and change in circulating CD34+ cells at 12-week follow-up. Outcomes are also measured at six-week and six-month follow-up. Results of the PROPEL Study will have important implications for understanding mechanisms of improving walking performance and preventing mobility loss in the large and growing number of men and women with PAD.
doi:10.1016/j.cct.2013.09.011
PMCID: PMC3939047  PMID: 24080099
11.  Association of Inflammation With Loss Of Ability to Walk 400 Meters: Longitudinal Findings From the Inchianti Study 
Objectives
To examine relationships between eight markers of inflammation (interleukin [IL]-6, IL-6 receptor [R], C-reactive protein [CRP], tumor necrosis factor [TNF]-α, TNF receptor 1[R1], TNFR2, IL-1 receptor antagonist, IL-18) and incident loss of ability to walk 400 m.
Design
Prospective cohort study.
Setting
Older adults enrolled in the InvecchiareInChianti Study.
Participants
One thousand six community-dwelling participants aged 65+.
Measurements
The eight inflammatory markers were measured at baseline, and an inflammation score was calculated based on the number of inflammatory markers for which the participant was in the highest quartile. Incidence of mobility disability was determined among participants able to walk 400 m at baseline. Logistic regression models were used to determine whether each of the inflammatory markers and the inflammation score predicts loss of the ability to walk 400 m at six-year follow-up.
Results
After adjusting for covariates, individuals with aTNFR1 level in each of the top 3 quartiles (Q2, 3, 4) were more likely to be unable to walk 400 m at follow-up compared to those with TNFR1 levels in Q1. When adjusting for the same covariates, participants with an inflammation score of 3 or 4 were more likely to become unable to complete the 400 m walk at follow-up compared to participants with a score of 0.
Conclusion
These results bring additional evidence to the notion that inflammation is implicated in the mechanisms that cause incident mobility disability and suggest that a combined measure of inflammatory markers may improve our prediction of functional prognosis.
doi:10.1111/jgs.12446
PMCID: PMC3801413  PMID: 24083386
inflammation; mobility; 400 m walk; functional limitation; aging
12.  Long-term Survival in Adults Aged 65 and Older With White Matter Hyperintensity: Association With Performance on the Digit Symbol Substitution Test 
Psychosomatic medicine  2013;75(7):10.1097/PSY.0b013e31829c1df2.
OBJECTIVE
White matter hyperintensity (WMH) confers increased mortality risk in patients with cardiovascular diseases. However, little is known about differences in survival times among adults 65 years and older who have WMH and live in the community. To characterize the factors that may reduce mortality risk in the presence of WMH, measures of race, sex, ApoE4, neuroimaging, cardiometabolic, physiological and psychosocial characteristics were examined, with a particular focus on information processing as measured by the Digit Symbol Substitution Test(DSST).
METHODS
Cox-proportional models were used to estimate mortality risks in a cohort of 3513 adults (74.8years, 58%women, 84%white) with WMH (0–9 points), DSST (0–90 points), risk factor assessment in 1992–94 and data on mortality and incident stroke to 2009 (median follow-up [range]:14.2[0.5–18.1]years).
RESULTS
WMH predicted a 48% greater mortality risk (age-adjusted hazard ratio (HR)[95% confidence interval(CI)] for WMH>3 points=1.48[1.35–1.62]). This association was attenuated after adjustment for DSST (HR[CI]: 1.38[1.27–1.51]) or lacunar infarcts (HR[CI]: 1.37[1.25,1.50]) but not after adjustment for other factors. The interaction between DSST and WMH was significant (p=0.011). In fully adjusted models stratified by WMH>3, participants with DSST>median had a 34% lower mortality risk among those with WMH>3 (n=532/1217) and a 28% lower mortality risk among those with WMH<3 (n=1364/2296), compared to participants with DSST
CONCLUSION
WMH is associated with increased long-term mortality risk in community-dwelling adults aged 65 and older. The increased risk is attenuated for those with higher DSST. Assessment of cognitive function with DSST may improve risk stratification of individuals with WMH.
doi:10.1097/PSY.0b013e31829c1df2
PMCID: PMC3809761  PMID: 23886735
mortality; information processing; white matter hyperintensity
PLoS ONE  2014;9(8):e102299.
Background
This study examines the associations between lifecourse adversity and physical performance in old age in different societies of North and South America and Europe.
Methods
We used data from the baseline survey of the International Study of Mobility in Aging, conducted in: Kingston (Canada), Saint-Hyacinthe (Canada), Natal (Brazil), Manizales (Colombia) and Tirana (Albania). The study population was composed of community dwelling people between 65 and 74 years of age, recruiting 200 men and 200 women at each site. Physical Performance was assessed with the Short Physical Performance Battery (SPPB). Economic and social adversity was estimated from childhood adverse events, low education, semi-skilled occupations during adulthood and living alone and insufficient income in old age.
Results
A total of 1995 people were assessed. Low physical performance was associated with childhood social and economic adversity, semi-skilled occupations, living alone and insufficient income. Physical performance was lower in participants living in Colombia, Brazil and Albania than in Canada counterparts, despite adjustment for lifecourse adversity, age and sex.
Conclusions
We show evidence of the early origins of social and economic inequalities in physical performance during old age in distinct populations and for the independent and cumulative disadvantage of low socioeconomic status during adulthood and poverty and living alone in later life.
doi:10.1371/journal.pone.0102299
PMCID: PMC4125146  PMID: 25101981
This study examined if inability to perform adaptive locomotor tests predicts self-reported incident mobility disability. InCHIANTI study participants (n=611, age: 50–85 years) who could walk 7 m at self-selected speed and had no self-reported mobility disability at baseline were included. Ability to complete 4 adaptive locomotor tests was assessed: fast walking, walking on a narrow path, crossing obstacles while walking and talking while walking. Mobility disability was recorded again at 3-year follow-up. Failure in fast walking and narrow-path walking tests predicted ~2.5 times likelihood of reporting incident mobility disability (p=0.009 and 0.011, respectively). Failure in obstacle crossing test predicted ~2 times likelihood of reporting incident mobility disability, however, this result did not reach statistical significance (p=0.077). Failure in talking while walking did not predict incident mobility disability. Those who failed both fast walking and narrow-path walking tests were almost 9 times as likely to report incident mobility disability.
doi:10.1097/PHM.0b013e31827d634e
PMCID: PMC3632651  PMID: 23291600
Mobility; Disability; Aging
BACKGROUND
Higher intake of fruits and vegetables appears to protect against inflammation, poor physical performance, and disability, but their relationship with muscle strength is unclear. We examined the association between total plasma carotenoids, an indicator of fruit and vegetable intake, and changes in muscle strength over a 6-year follow-up in the participants aged 65 years and older in the InCHIANTI study, a population-based study in Tuscany, Italy.
METHODS
Plasma carotenoids were measured at enrollment (1998–2000). Hip, knee and grip strength were measured at enrollment and 6 years later (2004–2006) in 628 of the 948 participants evaluated at baseline. Poor muscle strength was defined as the lowest sex-specific quartile of hip, knee and grip strength at enrollment. The main outcome was poor muscle strength at the six-year follow-up visit among those originally in the upper three quartiles of strength at enrollment.
RESULTS
Overall, 24.9% (110/441), 25.0% (111/444) and 24.9% (118/474) participants developed poor hip, knee and grip strength, respectively. After adjusting for potential confounders, participants in the lowest vs. the highest quartile of total plasma carotenoids at enrollment were at higher risk of developing poor hip (O.R. 2.25, 95% C.I. 1.13–4.48, P = 0.02), knee (O.R. 2.12, 95% C.I. 1.08–4.09, P = 0.03) and grip (O.R. 1.85, 95% C.I. 0.95–3.61, P = 0.07) muscle strength at the six-year follow-up visit.
CONCLUSION
These findings suggest that older community-dwelling adults with lower plasma carotenoids levels, a marker of poor fruit and vegetable intake, are at a higher risk of decline in skeletal muscle strength over time.
PMCID: PMC4101895  PMID: 18426961
carotenoids; InCHIANTI study; fruit; vegetable; sarcopenia
Frailty is a clinical state in which there is an increase in an individual’s vulnerability for developing increased dependency and/or mortality when exposed to a stressor. Frailty can occur as the result of a range of diseases and medical conditions. A consensus group consisting of delegates from 6 major international, European, and US societies created 4 major consensus points on a specific form of frailty: physical frailty. Physical frailty is an important medical syndrome. The group defined physical frailty as “a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death.”Physical frailty can potentially be prevented or treated with specific modalities, such as exercise, protein-calorie supplementation, vitamin D, and reduction of polypharmacy.Simple, rapid screening tests have been developed and validated, such as the simple FRAIL scale, to allow physicians to objectively recognize frail persons.For the purposes of optimally managing individuals with physical frailty, all persons older than 70 years and all individuals with significant weight loss (≥5%) due to chronic disease should be screened for frailty.
doi:10.1016/j.jamda.2013.03.022
PMCID: PMC4084863  PMID: 23764209
Frailty; physical frailty; rapid screening tests; weight loss; comorbidities
Background
Common variation at chromosome 9p21 (marked by rs10757278 or rs1333049) is associated with coronary artery disease (CAD) and peripheral vascular disease. A decreasing effect at older age was suggested, and effects on long-term mortality are unclear. We estimated 9p21 associations with CAD and all-cause mortality in a CAD diagnosis–free older population. We also estimated classification gains on adding the variant to the Framingham Risk Score (FRS) for CAD.
Methods and Results
DNA was from an Established Populations for Epidemiological Study of the Elderly–Iowa cohort from 1988 (participants >71 years), with death certificates obtained to 2008 for 92% of participants. Cox regression models were adjusted for confounders and CAD risk factors. Of 1095 CAD diagnosis–free participants, 52% were heterozygous (CG) and 22% were homozygous (CC) for the risk C allele rs1333049. Unadjusted CAD-attributed death rates in the CC group were 30 vs 22 per 1000 person-years for the GG group. The C allele was associated with all-cause (hazard ratio, 1.19; 95% CI, 1.08–1.30) and CAD (hazard ratio, 1.29; 95% CI, 1.08–1.56) mortality, independent of CAD risk factors. There was no association with stroke deaths. Variant associations with CAD mortality were attenuated after the age of 80 years (age-interaction term P=0.05). In age group 71 to 80 years, FRS classified as high risk 21% of respondents who died of CAD within 10 years; adding 9p21 identified 27% of respondents.
Conclusions
In 71- to 80-year-old subjects free of CAD diagnoses, 9p21 is associated with excess mortality, mainly attributed to CAD mortality. Adding 9p21 to the FRS may improve the targeting of CAD prevention in older people, but validation in independent samples is needed for confirmation.
doi:10.1161/CIRCGENETICS.111.960146
PMCID: PMC4053863  PMID: 21852414
coronary artery disease; genetic variation; myocardial infarction; survival; Framingham Risk Score
Objectives
The relationship between thyroid dysfunction and mortality in elderly subjects is still undefined. In this population study we tested the hypothesis that in older subjects, living in a mildly iodine-deficient area, thyroid dysfunction may be associated with increased mortality independent of potential confounders.
Design
Longitudinal study
Setting
Community-based
Participants
Total of 951 subjects aged 65 years and older
Measurements
Plasma thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) concentrations and demographic features were evaluated in participants of the Aging in the Chianti Area (InCHIANTI) study, aged 65 years or older. Participants were classified according to thyroid function test. Kaplan-Meier survival and Cox proportional hazards models adjusted for confounders were used in the analysis.
Results
A total of 819 participants were euthyroid, 83 had Subclinical hyperthyroidism (SHyper), and 29 had Subclinical hypothyroidism (SHypo). Overt Hypo- and Hyperthyroidism were found in 5 and 15 subjects, respectively. During a median of six-years of follow-up, N 210 deaths occurred (22.1 %) of which 98 (46.6%) due to cardiovascular causes. Kaplan–Meier analysis revealed higher overall mortality for SHyper (P<0.04) as compared to euthyroid subjects. After adjusting for multiple confounders, participants with SHyper (Hazard Ratio[HR]:1.65; 95% Confidence Interval [CI]: 1.02–2.69) had significantly higher all-cause mortality than those with normal thyroid function. No significant association was found between SHyper and cardiovascular mortality.
In euthyroid subjects, TSH was found to be predictive of a reduced risk of all-cause mortality (HR: 0.76; 95% CI, 0.57–0.99)
Conclusion
SHyper is an independent risk factor for all-cause mortality in the older population. Low-normal circulating TSH should be carefully monitored in euthyroid elderly individuals.
doi:10.1111/jgs.12267
PMCID: PMC3686888  PMID: 23647402
subclinical hyperthyroidism; aging; mortality
JACC. Cardiovascular imaging  2013;6(6):687-694.
Objective
We studied associations of MRI-measured SFA occlusions with functional performance, leg symptoms, and collateral vessel number in PAD. We studied associations of collateral vessel number with functional performance in PAD.
Background
Associations of magnetic resonance imaging (MRI)-detected superficial femoral artery (SFA) occlusion and collateral vessel number with functional performance among individuals with peripheral artery disease (PAD) have not been reported.
Methods
457 participants with an ankle brachial index (ABI) < 1.00 had MRI measurement of the proximal SFA with twelve consecutive 2.5 millimeter cross-sectional images. An occluded SFA was defined as an SFA in which at least one segment was occluded. A non-occluded SFA was defined as absence of any occluded slices. Collateral vessels were visualized with magnetic resonance angiography (MRA). Lower extremity functional performance was measured with the six-minute walk, four-meter walking velocity at usual and fastest pace, and the short physical performance battery (SPPB) (0-12 scale, 12=best).
Results
Adjusting for age, sex, race, comorbidities, and other confounders, the presence of an SFA occlusion was associated with poorer six-minute walk performance (1,031 vs. 1,169 feet, P=0.006), slower fast-paced walking velocity (1.15 vs. 1.22 meters/second, P =0.042), and lower SPPB score (9.07 vs. 9.75, P=0.038) compared to the absence of an SFA occlusion. More numerous collateral vessels were associated with better six-minute walk performance (0-3 collaterals-1,064 feet, 4-7 collaterals-1,165 feet, ≥ 8 collaterals-1,246 feet, P trend=0.007), faster usual-paced walking speed (0-3 collaterals-0.84 meters/second, 4-7 collaterals-0.88 meters/second, ≥ 8 collaterals-0.91 meters/second, P trend=0.029), and faster rapid-paced walking speed (0-3 collaterals-1.17 meters/second, 4-7 collaterals-1.22 meters/second, ≥ 8 collaterals-1.29 meters/second, P trend=0.002), adjusting for age, sex, race, comorbidities, ABI, and other confounders.
Conclusions
Among PAD participants, MRI-visualized occlusions in the proximal SFA are associated with poorer functional performance, while more numerous collaterals are associated with better functional performance.
Clinical Trial ID
NCT00520412
doi:10.1016/j.jcmg.2012.10.024
PMCID: PMC3766720  PMID: 23647796
atherosclerotic plaque; intermittent claudication; peripheral arterial disease; physical functioning
Background
We studied whether a 6‐month group‐mediated cognitive behavioral (GMCB) intervention for peripheral artery disease (PAD) participants, which promoted home‐based walking exercise, improved 6‐minute walk and other outcomes at 12‐month follow‐up, 6 months after completing the intervention, compared to a control group.
Methods and Results
We randomized PAD participants to a GMCB intervention or a control group. During phase I (months 1 to 6), the intervention used group support and self‐regulatory skills during weekly on‐site meetings to help participants adhere to home‐based exercise. The control group received weekly on‐site lectures on topics unrelated to exercise. Primary outcomes were measured at the end of phase I. During phase II (months 7 to 12), each group received telephone contact. Compared to controls, participants randomized to the intervention increased their 6‐minute walk distance from baseline to 12‐month follow‐up, (from 355.4 to 381.9 m in the intervention versus 353.1 to 345.6 m in the control group; mean difference=+34.1 m; 95% confidence interval [CI]=+14.6, +53.5; P<0.001) and their Walking Impairment Questionnaire (WIQ) speed score (from 36.1 to 46.5 in the intervention group versus 34.9 to 36.5 in the control group; mean difference =+8.8; 95% CI=+1.6, +16.1; P=0.018). Change in the WIQ distance score was not different between the 2 groups at 12‐month follow‐up (P=0.139).
Conclusions
A weekly on‐site GMCB intervention that promoted home‐based walking exercise intervention for people with PAD demonstrated continued benefit at 12‐month follow‐up, 6 months after the GMCB intervention was completed.
Clinical Trial Registration
URL: ClinicalTrials.gov. Unique identifier: NCT00693940.
doi:10.1161/JAHA.113.000711
PMCID: PMC4309051  PMID: 24850615
behavior change; exercise; mobility; peripheral artery disease; physical functioning
We determined whether more adverse calf muscle characteristics and poorer peripheral nerve function were associated with impairments in self-perceived physical functioning and walking ability in persons with lower extremity peripheral arterial disease (PAD). Participants included 462 persons with PAD; measures included the ankle-brachial index (ABI), medical history, electrophysiologic characteristics of nerves, and computed tomography of calf muscle. Self-perceived physical functioning and walking ability were assessed using the 36-Item Short Form Health Survey (SF-36) and the Walking Impairment Questionnaire (WIQ). Results were adjusted for age, sex, race, ABI, body-mass index, comorbidities, and other confounders. Lower calf muscle area was associated with a poorer SF-36 physical function (PF) score (overall p trend<0.001, 33.76 PF score for the lowest quartile vs. 59.74 for the highest, pair wise p<0.001) and a poorer WIQ walking distance score (p trend=0.001, 29.71 WIQ score for the lowest quartile vs. 48.43 for the highest, pair wise p<0.001). Higher calf muscle percent fat was associated with a poorer SF-36 PF score (p trend<0.001, 53.76 PF score for the lowest quartile vs. 40.28 for the highest, pair wise p=0.009). Slower peroneal nerve conduction velocity was associated with a poorer WIQ speed score (p trend=0.023, 30.49 WIQ score for the lowest quartile vs. 40.48 for the highest, pair wise p=0.031). In summary, adverse calf muscle characteristics and poorer peripheral nerve function are associated significantly and independently with impairments in self-perceived physical functioning and walking ability in PAD persons.
doi:10.1177/1358863X10395656
PMCID: PMC4034534  PMID: 21471147
peripheral arterial disease; calf muscle characteristics; peripheral nerve function; quality of life
Objectives
To identify a standard physical performance test that can predict 3-year incident mobility disability (IMD) independent of demographics
Design
Longitudinal cohort study
Setting
Population-based older cohort
Participants
Community-living middle-aged and older persons (age: 50–85 years) without baseline mobility disability (n=622).
Measurements
Mobility disability was ascertained at baseline and at 3-year follow-up using an established self-report method: self-reported inability to walk a quarter mile without resting or inability to walk up a flight of stairs unsupported. Physical performance tests included self-selected usual gait speed, time required to complete 5 times sit-to-stand (5tSTS) and 400 m brisk walking. Demographic variables age, sex, height and weight were recorded.
Results
Overall, 13.5% participants reported 3-year IMD. Usual gait speed <1.2 m/s, requiring >13.6 seconds to complete 5tSTS and completing 400 m at <1.19m/s walking speed were highly predictive of future mobility disability independent of demographics.
Conclusions
Inability to complete 5tSTS in < 13.7 seconds can be a clinically convenient guideline for monitoring and for further assessment of middle-aged and older persons, in order to prevent or delay future mobility disability.
doi:10.1016/j.apmr.2012.10.032
PMCID: PMC3637852  PMID: 23164980
mobility; disability; aging
Interventions which inhibit TOR activity (including rapamycin and caloric restriction) lead to downstream gene expression changes and increased lifespan in laboratory models. However, the role of mTOR signaling in human aging is unclear.
We tested the expression of mTOR-related transcripts in two independent study cohorts; the InCHIANTI population study of aging and the San Antonio Family Heart Study (SAFHS). Expression of 27/56 (InCHIANTI) and 19/44 (SAFHS) genes were associated with age after correction for multiple testing. 8 genes were robustly associated with age in both cohorts. Genes involved in insulin signaling (PTEN, PI3K, PDK1), ribosomal biogenesis (S6K), lipid metabolism (SREBF1), cellular apoptosis (SGK1), angiogenesis (VEGFB), insulin production and sensitivity (FOXO), cellular stress response (HIF1A) and cytoskeletal remodeling (PKC) were inversely correlated with age, whereas genes relating to inhibition of ribosomal components (4EBP1) and inflammatory mediators (STAT3) were positively associated with age in one or both datasets.
We conclude that the expression of mTOR-related transcripts is associated with advancing age in humans. Changes seen are broadly similar to mTOR inhibition interventions associated with increased lifespan in animals. Work is needed to establish whether these changes are predictive of human longevity and whether further mTOR inhibition would be beneficial in older people.
doi:10.1016/j.mad.2012.07.003
PMCID: PMC3998676  PMID: 22813852
Aging; aging mechanisms; mTOR; human population
Objective
Diabetes among older adults causes many complications, including decreased lower extremity function and physical disability. Diabetes can cause peripheral nerve dysfunction, which might be one pathway through which diabetes leads to decreased physical function. The study aims were to determine: (1) whether diabetes and impaired fasting glucose are associated with objective measures of physical function in older adults, (2) which peripheral nerve function (PNF) tests are associated with diabetes, and (3) whether PNF mediates the diabetes-physical function relationship.
Research Design and Methods
This study included 983 participants, age 65 and older from the InCHIANTI Study. Diabetes was diagnosed by clinical guidelines. Physical performance was assessed using the Short Physical Performance Battery (SPPB), scored from 0-12 (higher values, better physical function) and usual walking speed (m/s). PNF was assessed via standard surface electroneurographic study of right peroneal nerve conduction velocity, vibration and touch sensitivity. Clinical cut-points of PNF tests were used to create a neuropathy score from 0-5 (higher values, greater neuropathy). Multiple linear regression models were used to test associations.
Results and Conclusion
12.8% (n=126) of participants had diabetes. Adjusting for age, sex, education, and other confounders, diabetic participants had decreased SPPB (β= −0.99; p< 0.01), decreased walking speed (β= −0.1m/s; p< 0.01), decreased nerve conduction velocity (β= −1.7m/s; p< 0.01), and increased neuropathy (β= 0.25; p< 0.01) compared to non-diabetic participants. Adjusting for nerve conduction velocity and neuropathy score decreased the effect of diabetes on SPPB by 20%, suggesting partial mediation through decreased PNF.
doi:10.1016/j.jdiacomp.2013.08.007
PMCID: PMC3987662  PMID: 24120281
Background.
Physical activity (PA) appears to have a positive effect on physical function, however, studies have not examined multiple indices of physical function jointly nor have they conceptualized physical functioning as a state rather than a trait.
Methods.
About 424 men and women aged 70–89 were randomly assigned to complete a PA or a successful aging (SA) education program. Balance, gait speed, chair stand performance, grip strength, and time to complete the 400-m walk were assessed at baseline and at 6 and 12 months. Using hidden Markov model, empiric states of physical functioning were derived based on these performance measures of balance, strength, and mobility. Rates of gain and loss in physical function were compared between PA and SA.
Results.
Eight states of disability were identified and condensed into four clinically relevant states. State 1 represented mild disability with physical functioning, states 2 and 3 were considered intermediate states of disability, and state 4 severe disability. About 30.1% of all participants changed states at 6 months, 24.1% at 12 months, and 11.0% at both time points. The PA group was more likely to regain or sustain functioning and less likely to lose functioning when compared with SA. For example, PA participants were 20% more likely than the SA participants to remain in state 1.
Conclusion.
PA appears to have a favorable effect on the dynamics of physical functioning in older adults.
doi:10.1093/gerona/gls186
PMCID: PMC3593616  PMID: 22987794
Older adults; Physical activity; Randomized controlled trial; Physical functioning; Transitional states.

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