Ingestion of ß-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind randomized, placebo-controlled study.

The study evaluated how ingestion of nicotinamide mononucleotide (NMN) for 12 weeks by older adults affected blood nicotinamide adenine dinucleotide (NAD +) levels and physical function, particularly walking function. Information concerning sleep, and stress was also collected as secondary endpoints. In this randomized, placebo-controlled, double-blind, parallel-group comparison study, 60 participants were randomly allocated into a placebo group or NMN group. Members of the NMN group consumed 250 mg/day NMN for 12 weeks. Motor function tests, blood NAD metabolite analysis, and questionnaires were conducted at the start of the study and 4 and 12 weeks after intake. This trial was registered at umin.ac.jp/ctr as UMIN000047871 on June 22nd, 2022.At primary outcome, at both 4 weeks and 12 weeks, the NMN and placebo groups had no significant differences in a stepping test. At secondary outcomes, after 12 weeks of NMN intake, the NMN group had a significantly shorter 4-m walking time than the placebo group as well as significantly higher blood levels of NAD + and its metabolites. A significant negative correlation was observed between the change in the 4-m walking time and the change in blood NAD + , N1-methyl-2-pridone-5-carboxamide (2-PY), and N1-methyl-4-pridone-3-carboxamide (4-PY) at 12 weeks. The NMN group had improved sleep quality at 12 weeks relative to the placebo group as evidenced by lower scores for "Daytime dysfunction" and "Global PSQI" on the Pittsburgh Sleep Questionnaire. No adverse effects related to test substance consumption were observed. Together, these results indicate that NMN intake could increase blood NAD + levels, maintain walking speed, and improve sleep quality in older adults. Interventions involving NMN aimed at maintaining walking speed could contribute to extended healthy life expectancy.

Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study.

OBJECTIVE: Nicotinamide adenine dinucleotide regulates various biological processes. Nicotinamide mononucleotide (NMN) increases its intracellular levels and counteracts age-associated changes in animal models. We investigated the safety and efficacy of oral nicotinamide mononucleotide supplementation in older patients with diabetes and impaired physical performance. METHOD: We carried out a 24-week placebo-controlled, double-blinded study of male patients with diabetes aged ≥65 years with reduced grip strength (<26 kg) or walking speed (<1.0 m/s). The primary end-points were to determine the safety of NMN oral administration (250 mg/day), and changes in grip strength and walking speed. The secondary end-points were to determine the changes in various exploratory indicators. RESULTS: We studied 14 participants aged 81.1 ± 6.4 years. NMN was tolerable without any severe adverse events. The changes in grip strength and walking speed showed no difference between the two groups: 1.25 kg (95% confidence interval -2.31 to 4.81) and 0.033 m/s (-0.021 to 0.087) in the NMN group, and -0.44 kg (-4.15 to 3.26) and 0.014 m/s (-0.16 to -0.13) in the placebo group, respectively. There were no significant differences in any exploratory indicators between the two groups. However, improved prevalence of frailty in the NMN group (P = 0.066) and different changes in central retinal thickness between the two groups (P = 0.051) was observed. CONCLUSION: In older male patients with diabetes and impaired physical performance, NMN supplementation for 24 weeks was safe, but did not improve grip strength and walking speed. Geriatr Gerontol Int 2023; 23: 38-43.

Effect of n-3 polyunsaturated fatty acid supplementation on muscle mass and function with aging: A meta-analysis of randomized controlled trials✰.

The results of randomized controlled trials (RCTs) investigating supplemental n-3 polyunsaturated fatty acids (PUFA) on muscle mass and function have been inconsistent. The present study aimed to quantitatively evaluate the effect of n-3 PUFA supplementation on indicators of muscle mass and function in healthy subjects. A systematic literature search was conducted up to July 2020 with databases of PubMed and Web of science. The random-effects model was implemented to calculate the weighted mean difference of net change of indicators regarding muscle mass and function. A total of nine studies (thirteen treatment groups) with 2067 participants were included for data analysis. The summary estimate showed that n-3 PUFA supplementation significantly increased the grip strength (1.17 kg; 95% CI: 0.27, 2.08 kg). Non-significant effect was observed with respect to muscle mass parameters, including fat mass (-0.67 kg; 95% CI: -2.20, 0.87 kg) and lean mass (0.33 kg; 95% CI: -0.35, 1.00 kg). Regarding muscle function indicators, there were non-significant effects on walking speed (-0.01 m•s-1; 95% CI: -0.03, 0.01 m•s-1), time up and go test (-0.25 s; 95% CI: -0.55, 0.04 s), respectively. The findings of this study indicated that supplementation with n-3 PUFA might have beneficial effects to improve muscle mass and function in healthy participants. However, there was no significant improvement in the subjects' muscle mass. Whether n-3 PUFA supplementation has favorable effects in participants with sarcopenia are warranted to be further investigated.

Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: There is an unmet need to develop therapeutic interventions directed at the neurodegeneration that underlies progression in multiple sclerosis. High-dose, pharmaceutical-grade biotin (MD1003) might enhance neuronal and oligodendrocyte energetics, resulting in improved cell function, repair, or survival. The MS-SPI randomised, double-blind, placebo-controlled study found that MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis. The SPI2 study was designed to assess the safety and efficacy of MD1003 in progressive forms of multiple sclerosis in a larger, more representative patient cohort. METHODS: SPI2 was a randomised, double-blind, parallel-group, placebo-controlled trial done at 90 academic and community multiple sclerosis clinics across 13 countries. Patients were aged 18-65 years, had a diagnosis of primary or secondary progressive multiple sclerosis fulfilling the revised International Panel criteria and Lublin criteria, a Kurtzke pyramidal functional subscore of at least 2 (defined as minimal disability), an expanded disability status scale (EDSS) score of 3·5-6·5, a timed 25-foot walk (TW25) of less than 40 s, evidence of clinical disability progression, and no relapses in the 2 years before enrolment. Concomitant disease-modifying therapies were allowed. Patients were randomly assigned (1:1) by an independent statistician using an interactive web response system, with stratification by study site and disease history, to receive MD1003 (oral biotin 100 mg three times daily) or placebo. Participants, investigators, and assessors were masked to treatment assignment. The primary endpoint was a composite of the proportion of participants with confirmed improvement in EDSS or TW25 at month 12, confirmed at month 15, versus baseline. The primary endpoint was assessed in the intention-to-treat analysis set, after all participants completed the month 15 visit. Safety analyses included all participants who received at least one dose of MD1003. This trial is registered with ClinicalTrials.gov (NCT02936037) and the EudraCT database (2016-000700-29). FINDINGS: From Feb 22, 2017, to June 8, 2018, 642 participants were randomly assigned MD1003 (n=326) or placebo (n=316). The double-blind, placebo-controlled phase of the study ended when the primary endpoint for the last-entered participant was assessed on Nov 15, 2019. The mean time in the placebo-controlled phase was 20·1 months (SD 5·3; range 15-27). For the primary outcome, 39 (12%) of 326 patients in the MD1003 group compared with 29 (9%) of 316 in the placebo group improved at month 12, with confirmation at month 15 (odds ratio 1·35 [95% CI 0·81-2·26]). Treatment-emergent adverse events occurred in 277 (84%) of 331 participants in the MD1003 group and in 264 (85%) of 311 in the placebo group. 87 (26%) of 331 participants in the MD1003 group and 82 (26%) of 311 participants in the placebo group had at least one serious treatment-emergent adverse event. One (<1%) person died in the MD1003 group and there were no deaths in the placebo group. Despite use of mitigation strategies, MD1003 led to inaccurate laboratory results for tests using biotinylated antibodies. INTERPRETATION: This study showed that MD1003 did not significantly improve disability or walking speed in patients with progressive multiple sclerosis and thus, in addition to the potential of MD1003 for deleterious health consequences from interference of laboratory tests, MD1003 cannot be recommended for treatment of progressive multiple sclerosis. FUNDING: MedDay Pharmaceuticals.

Elastic-band resistance exercise or vibration treatment in combination with hydroxymethylbutyrate (HMB) supplement for management of sarcopenia in older people: a study protocol for a single-blinded randomised controlled trial in Hong Kong.

INTRODUCTION: Sarcopenia is a geriatric syndrome characterised by progressive loss of skeletal muscle mass and function with risks of adverse outcomes and becomes more prevalent due to ageing population. Elastic-band exercise, vibration treatment and hydroxymethylbutyrate (HMB) supplementation were previously proven to have positive effects on the control of sarcopenia. The purpose of this study is to evaluate the effectiveness of elastic-band exercise or vibration treatment with HMB supplementation in managing sarcopenia. Our findings will provide a safe and efficient strategy to mitigate the progression of sarcopenia in older people and contribute to higher quality of life as well as improved long-term health outcomes of elderly people. METHODS AND ANALYSIS: In this single-blinded, randomised controlled trial (RCT), subjects will be screened for sarcopenia based on the Asian Working Group for Sarcopenia (AWGS) definition and 144 sarcopenic subjects aged 65 or above will be recruited. This RCT will have three groups evaluated at two time points to measure changes over 3 months-the control and the groups with combined HMB supplement and elastic-band resistance exercise or vibration treatment. Changes in muscle strength in lower extremity will be the primary outcome. Muscle strength in the upper extremity, gait speed, muscle mass (based on AWGS definition), functional performance in terms of balancing ability and time-up-and-go test and quality of life will be taken as secondary outcomes. In addition, each participant's daily activity will be monitored by a wrist-worn activity tracker. Repeated-measures analysis of variance will be performed to compare within-subject changes between control and treatment groups at two time points of pretreatments and post-treatments. ETHICS AND DISSEMINATION: The procedures have been approved by the Joint CUHK-NTEC Clinical Research Management Office (Ref. CREC 2018.602) and conformed to the Declaration of Helsinki. Results will be disseminated through peer-reviewed publications, conferences and workshops. TRIAL REGISTRATION NUMBER: NCT04028206.

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

OBJECTIVE: 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. DESIGN: Longitudinal study (three waves). SETTING: The Irish Longitudinal Study on Ageing (TILDA), a nationally representative cohort study. PARTICIPANTS: Two thousand ninety-three community-dwelling adults aged ≥60 years. MEASUREMENTS: 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. RESULTS: 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. CONCLUSION: 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.

Does Use of Androgen Deprivation Therapy (ADT) in Men with Prostate Cancer Increase the Risk of Sarcopenia?

Androgen deprivation therapy (ADT) for prostate cancer (PCa) can compromise muscle health. Hence, we aimed to quantify the prevalence of sarcopenia (i.e., compromised lean mass, muscle strength, and physical function) in ADT-treated (> 12 week) men (n = 70) compared to similarly aged non-ADT-treated PCa (n = 52) and healthy controls (n = 70). Lean and fat mass were quantified by dual-energy X-ray absorptiometry. Muscle strength and function were measured using handgrip dynamometry and gait speed, respectively. Sarcopenia was defined as low adjusted appendicular lean mass [ALM; height-adjusted (ALMI), body mass index-adjusted (ALMBMI) and height and fat mass-adjusted (ALMHFM)] with weak handgrip strength and/or slow gait speed according to the following criteria: European Working Group on Sarcopenia in Older People [EWGSOP; both 2010 (EWGSOP1) and 2018 (EWGSOP2)], Foundation for the National Institutes of Health (FNIH) and International Working Group on Sarcopenia (IWGS). Overall the prevalence of sarcopenia was low and did not differ between the three groups. Only two (3.2%) ADT-treated men presented with sarcopenia as per EWGSOP1 and FNIH criteria, whereas no cases were observed using EWGSOP2 and IWGS criteria. The prevalence of low ALMBMI was greater in ADT-treated men (32%) compared to PCa (15%; P = 0.037) and healthy controls (7.1%; P < 0.001). Similarly, low ALMHFM was greater in ADT-treated men (29%) compared to healthy controls only (13%; P = 0.019). There was also a low prevalence of weak muscle strength and slow gait speed (0.0-11%) in all men, with no differences between the groups. Based on these findings, an adiposity-based adjustment of ALM is recommended to quantify risk of adverse outcomes associated with ADT in these men.

Polypharmacy and gait speed in individuals with mild cognitive impairment.

AIM: Polypharmacy has been reported to be associated with poor outcomes, including falls and frailty, in older populations. Past studies have found that slower walking speed is a good predictor of progression to frank dementia in mild cognitive impairment (MCI). Some studies of the general population reported that polypharmacy was associated with slower gait speed; however, it remains to be elucidated whether polypharmacy affects gait speed even in individuals with MCI, who already have some deterioration in gait compared with cognitively preserved individuals. The current study explored the association between the number of medications and gait speed in older adults with MCI who have a Clinical Dementia Rating score of 0.5. METHODS: A total of 128 individuals with MCI were included in the present study. The participants were divided into three groups according to the number of medications they were taking: up to four medications was non-polypharmacy; five to nine medications was polypharmacy; and ≥10 medications was hyperpolypharmacy. The background characteristics were compared by analysis of variance for numerical numbers, and by χ2 analysis for categorical factors. Multiple regression and logistic analysis were applied to investigate the association between gait speed and polypharmacy status or number of medications. RESULTS: Gait speed was significantly negatively associated with hyperpolypharmacy status and the number of medications. Slow gait speed (<1 m/s) was also significantly associated with polypharmacy status and the number of medications. CONCLUSIONS: We found that polypharmacy was associated with slow gait speed in older adults with MCI. Geriatr Gerontol Int 2019; 19: 730-735.

High relative consumption of vegetable protein is associated with faster walking speed in well-functioning older adults.

BACKGROUND: Adequate nutrition and, especially, optimal protein intake are necessary to preserve physical function during aging. Increased consumption of animal-derived protein is often advocated as a strategy to support physical performance in old age. However, there is a lack of empirical evidence to support this claim. AIMS: To assess the relationship of protein consumption and specific protein sources with physical function in older adults. METHODS: Participants were community dwellers aged 60 years and older recruited in São Paulo, Brazil. Enrollees had their medical books reviewed and were evaluated for anthropometry, physical performance, and diet. Physical performance was evaluated by isometric handgrip strength and walking speed (WS) tests. Diet was assessed using a 24-h recall diary. RESULTS: Ninety older adults were recruited (mean age: 68.0 ± 6.7 years; 87.0% women). Body weight-adjusted protein consumption was significantly associated with upper-limb muscle strength (r = 0.21; p < 0.05), but not with usual (r = 0.09; p > 0.05) or fast WS (r = 0.08; p > 0.05). Conversely, relative protein consumption was correlated with usual WS (r = 0.13; p < 0.05), while fast WS was negatively associated with relative animal protein intake (r = - 0.18; p < 0.05) and positively associated with relative plant-based protein ingestion (r = 0.15; p < 0.05). DISCUSSION: Findings of the present study indicate that different measures of protein intake are associated with distinct components of physical function. In addition, high relative ingestion of vegetable protein is associated with faster WS. CONCLUSIONS: A comprehensive dietary evaluation is necessary to appreciate the impact of specific nutrients on physical performance in older people. Future interventional studies are needed to establish the optimal blend of protein sources to support physical performance in old age.

Factors affecting walking ability in female patients with rheumatoid arthritis.

OBJECTIVE: To determine the factors associated with gait parameters in female patients with rheumatoid arthritis (RA). METHODS: The gait analysis was performed in a large cohort of RA patients, and three basic gait parameters (step length, cadence and gait speed) were calculated. Clinical and laboratory data were also collected. Factors associated with gait parameters were analyzed using multivariable linear regression in the three models with forced entry. Then, we divided those patients with Health Assessment Questionnaire disability index (HAQ) scores ≤ 0.5 into two groups according to their gait speed that were compared to identify the characteristics of patients with a good HAQ score but poor walking ability. RESULTS: A total of 318 female patients were analyzed. Knee extension strength had the strongest positive association with all three gait parameters (P < 0.0001), while methotrexate use was also positively associated with all three gait parameters (step length: P < 0.05, cadence: P < 0.05 in model 1 and 2; P < 0.01 in model 3, gait speed: P < 0.01). The disease activity score was negatively associated with step length and gait speed (step length, gait speed: P < 0.01 in model 1 and 2; P < 0.05 in model 3). 26% of patients with good HAQ scores showed slow gait speed. Patients with good HAQ scores and slow gait speed had higher disease activity scores (P < 0.05) and lower knee extension strength (P < 0.0001) than those with good HAQ scores and normal gait speed. CONCLUSIONS: High knee extension strength, low disease activity and administration of methotrexate were strongly associated with good walking ability in female patients with RA. And, even if patients showed good HAQ scores, about quarter of those patients had poor walking ability, and they showed higher disease activity, lower knee extension strength, compared to the patients with normal gait speed.

Functional outcomes following ultrasound-guided botulinum toxin type A injections to reduce spastic equinovarus in adult post-stroke patients.

OBJECTIVE: The aim of this study is to identify the effect on spasticity and walking of US-guided botulinum toxin type A (BoNT-A) injections administered to improve equinovarus walking pattern commonly observed in patients after stroke. MATERIAL AND METHOD: Twenty-three patients with post-stroke spastic equinovarus deformity were recruited. The US-guided BoNT-A injections were administered into the spastic muscles (including gastrocnemius; GK, soleus; S and tibialis posterior; TP) using a specific approach, and all of the patients were enrolled in rehabilitation programmes after the injections. Modified Ashworth Scale (MAS), Brunnstrom stage of lower limb, Functional Ambulation Score (FAS), Preferred Gait Speed (PGS) and the six-minute walk test (6MWT) were assessed at the baseline, 4 and 12 weeks after the BoNT-A injection. RESULTS: Significant decreases in the MAS scores of the lower limb muscle (GK, S and TP) tone were measured 4 and 12 weeks after the BoNT-A injection when compared to the baseline scores (p < 0.05). In parallel with a reduction in spasticity there was an increase in 6MWT and PGS in the 4th and 12th weeks. Increases in motor improvement and functional ambulation score were ensured in the 12th week (p < 0.05). CONCLUSION: Spastic equinovarus deformity observed in patients after stroke creates significant limitations in the patient's functional walking speed and distance. As a result, when BoNT-A injections accompanied by ultrasound to improve equinovarus deformity considering the innervation zones of the muscles with a specific approach are administered directly into the muscle at the correct point, we can say it provides hopeful results from a functional point of view.

Effects of Low-Dose Dairy Protein Plus Micronutrient Supplementation during Resistance Exercise on Muscle Mass and Physical Performance in Older Adults: A Randomized, Controlled Trial.

OBJECTIVES: To investigate whether supplementation with low-dose dairy protein plus micronutrients augments the effects of resistance exercise (RE) on muscle mass and physical performance compared with RE alone among older adults. DESIGN: Randomized controlled trial. SETTING: Tokyo, Japan. PARTICIPANTS: Eighty-two community-dwelling older adults (mean age, 73.5 years) were randomly allocated to an RE plus dairy protein and micronutrient supplementation group or an RE only group (n = 41 each). INTERVENTION: The RE plus supplementation group participants ingested supplements with dairy protein (10.5 g/day) and micronutrients (8.0 mg zinc, 12 µg vitamin B12, 200 µg folic acid, 200 IU vitamin D, and others/day). Both groups performed the same twice-weekly RE program for 12 weeks. MEASUREMENTS: Whole-body, appendicular, and leg lean soft-tissue mass (WBLM, ALM, and LLM, respectively) with dual-energy X-ray absorptiometry, physical performance, biochemical characteristics, nutritional intake, and physical activity were measured before and after the intervention. Data were analyzed by using linear mixed-effects models. RESULTS: The groups exhibited similar significant improvements in maximum gait speed, Timed Up-and-Go, and 5-repetition and 30-s chair stand tests. As compared with RE only, RE plus supplementation significantly increased WBLM (0.63 kg, 95% confidence interval [CI]: 0.31-0.95), ALM (0.37 kg, 95% CI: 0.16-0.58), LLM (0.27 kg, 95% CI: 0.10-0.46), and serum concentrations of 25-hydroxyvitamin D (4.7 ng/mL, 95% CI: 1.6-7.9), vitamin B12 (72.4 pg/mL, 95% CI: 12.9-131.9), and folic acid (12.9 ng/mL, 95% CI: 10.3-15.5) (all P < 0.05 for group-by-time interactions). Changes over time in physical activity and nutritional intake excluding the supplemented nutrients were similar between groups. CONCLUSION: Low-dose dairy protein plus micronutrient supplementation during RE significantly increased muscle mass in older adults but did not further improve physical performance.

Blood and urine cadmium concentrations and walking speed in middle-aged and older U.S. adults.

Reduced physical performance is an important feature of aging, and walking speed is a valid measure of physical performance and mobility in older adults. Previous epidemiological studies suggest that cadmium exposure, even at low environmental levels, may contribute to vascular, musculoskeletal, and cognitive dysfunction, which may all be associated with reductions in physical performance. To this end, we investigated the associations of blood and urine cadmium concentrations with walking speed in middle-aged and older adults in the U.S. general population. We studied U.S. adults from the National Health and Nutrition Examination Survey 1999 to 2002 who were ≥50 years of age, who had determinations of cadmium in blood or in urine, and who had measurements of the time taken to walk 20 feet. Walking speed (ft/sec) was computed as walked distance (20 ft) divided by measured time to walk (in seconds). The weighted geometric means of blood and urine cadmium were 0.49 [95% confidence interval (CI): 0.47, 0.52] µg/L and 0.37 (95% CI: 0.34, 0.42) ng/mL, respectively. After adjusting for sociodemographic, anthropometric, health-related behavioral, and clinical risk factors and inflammation markers, the highest (vs. lowest) quintile of blood cadmium was associated with a 0.18 (95% CI: 0.10, 0.25) ft/sec reduction in walking speed (p-Trend <0.001). No association was observed for urine cadmium levels with walking speed. Cadmium concentrations in blood, but not in urine, were associated with slower gait speed. Our findings add to the growing volume of evidence supporting cadmium's toxicity even at low levels of exposure.

Relationships of depressive behavior and sertraline treatment with walking speed and activity in older female nonhuman primates.

Depression is the most common mental health problem in aging persons and is a leading risk factor for physical disability, especially in women. Though antidepressant drugs such as serotonin reuptake inhibitors (SSRI) are commonly prescribed, epidemiological evidence reveals mixed effects of long-term antidepressant use on physical function and activity, possibly depending on depressive status. The purpose of this preclinical trial was to determine the relationships of depressive behavior and the potential for an SSRI treatment to modulate walking speed and activity patterns in older adult female cynomolgus monkeys (Macaca fascicularis). We evaluated the effects of depression and a commonly prescribed SSRI, sertraline HCl (20 mg/kg/day p.o.), on (a) walking speed, (b) accelerometry-derived activity (counts) and sedentariness (daytime 60-s sedentary epochs), and (c) observed locomotor and sedentary behaviors (% time) in adult female depressed and nondepressed monkeys (n = 42; 17.2 ± 1.8 years) during an 18 month pre-treatment phase and an 18 month treatment phase using a longitudinal, stratified placebo-control study design. Monkeys that were depressed prior to treatment (19/42) subsequently had slower walking speeds (F D [1, 38] = 4.14; p ≤ 0.05) and tended to be more sedentary during the daytime (F D [1, 38] = 3.63; p ≤ 0.06). Sertraline did not affect depressive behaviors, walking speed, accelerometry-derived physical activity or sedentariness, or time observed in total locomotor or sedentary behavior (all p > 0.10). This study provides the first experimental demonstration of relationships between nonhuman primate behavioral depression and walking speed, activity, and sedentariness and provides evidence for a lack of an effect of SSRI treatment on these phenotypes.

Effect of Metformin on Handgrip Strength, Gait Speed, Myostatin Serum Level, and Health-related Quality of Life: A Double Blind Randomized Controlled Trial among Non-diabetic Pre-frail Elderly Patients.

BACKGROUND: sarcopenia contributes to the development of frailty syndrome. Frailty syndrome is potentially improved by modifying insulin resistance, inflammation, and myostatin level. This study is aimed to investigate the effect of metformin on handgrip strength, gait speed, myostatin serum level, and health-related quality of life (HR-QoL) among non-diabetic pre-frail elderly patients. METHODS: a double blind randomized controlled trial study was conducted on non-diabetic elderly outpatients aged ≥ 60 years with pre-frail status based on phenotype and/ or index criteria (Cardiovascular Health Study and/ or Frailty Index 40 items) consecutively recruited from March 2015 to June 2016 at Cipto Mangunkusumo Hospital. One-hundred-twenty subjects who met the research criteria were randomized and equally assigned into 3 x 500 mg metformin or placebo group. The study outcomes were measured at baseline and after 16 weeks of intervention. RESULTS: out of 120 subjects, 43 subjects in metformin group and 48 subjects in placebo group who completed the intervention. There was a significant improvement on the mean gait speed of metformin group by 0.39 (0.77) second or 0.13 (0.24) meter/second that remained significant after adjusting for important prognostic factors (p = 0.024). There was no significant difference on handgrip strength, myostatin serum level, and HR-QoL between both groups. CONCLUSION: 3 x 500 mg metformin for 16 weeks was statistically significant and clinically important in improving usual gait speed as one of the HR-QoL dimensions, but did not significantly improve the EQ-5D index score, handgrip strength, nor myostatin serum level.

Recuperation of slow walking in de novo Parkinson's disease is more closely associated with increased cadence, rather than with expanded stride length.

INTRODUCTION: Gait characteristics in the early stages of Parkinson's disease (PD) have been less investigated so far. Moreover, the levodopa effect on gait in early PD remains to be further elucidated. We prospectively designed the study to examine gait dynamics and effect of dopaminergic treatment in patients with de novo PD. METHODS: Spatiotemporal parameters were measured in healthy controls and drug naïve patients with PD, using computerized analysis with GAITRite system during usual gait. In PD group, motor symptoms and gait parameters were examined in both drug naive and levodopa 100mg trial conditions. RESULTS: Twenty four de novo PD patients and 27 healthy controls (matched for age, sex, and height) were selected for the study. Compared with the controls, patients with de novo PD showed the decrease in stride length, in both Med-OFF and Med-ON conditions. Notably, drug naïve patients with PD demonstrated slow walking velocity, whereas those with levodopa administration exhibited the increase of cadence by shortening stride time, which resulted in the improvement of gait speed. In addition, the stride length (gait hypokinesia) correlated with postural instability and gait difficulty subscore, but not with tremor, rigidity, bradykinesia, or total motor score. CONCLUSION: As a compensatory mechanism of slow walking, we found that the increment in cadence (frequency) is more important than the increment in stride length (amplitude) in gait dynamics in de novo PD. Additionally, the results may indicate that gait hypokinesia in PD could be regarded as one of axial symptoms.

Effect of Intensive Blood Pressure Control on Gait Speed and Mobility Limitation in Adults 75 Years or Older: A Randomized Clinical Trial.

Importance: Intensive blood pressure (BP) control confers a benefit on cardiovascular morbidity and mortality; whether it affects physical function outcomes is unknown. Objective: To examine the effect of intensive BP control on changes in gait speed and mobility status. Design, Setting, and Participants: This randomized, clinical trial included 2636 individuals 75 years or older with hypertension and no history of type 2 diabetes or stroke who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Data were collected from November 8, 2010, to December 1, 2015. Analysis was based on intention to treat. Interventions: Participants were randomized to intensive treatment with a systolic BP target of less than 120 mm Hg (n = 1317) vs standard treatment with a BP target of less than 140 mm Hg (n = 1319). Main Outcomes and Measures: Gait speed was measured using a 4-m walk test. Self-reported information concerning mobility was obtained from items on the Veterans RAND 12-Item Health Survey and the EQ-5D. Mobility limitation was defined as a gait speed less than 0.6 meters per second (m/s) or self-reported limitations in walking and climbing stairs. Results: Among the 2629 participants in whom mobility status could be defined (996 women [37.9%]; 1633 men [62.1%]; mean [SD] age, 79.9 [4.0] years), median (interquartile range) follow-up was 3 (2-3) years. No difference in mean gait speed decline was noted between the intensive- and standard-treatment groups (mean difference, 0.0004 m/s per year; 95% CI, -0.005 to 0.005; P = .88). No evidence of any treatment group differences in subgroups defined by age, sex, race or ethnicity, baseline systolic BP, chronic kidney disease, or a history of cardiovascular disease were found. A modest interaction was found for the Veterans RAND 12-Item Health Survey Physical Component Summary score, although the effect did not reach statistical significance in either subgroup, with mean differences of 0.004 (95% CI, -0.002 to 0.010) m/s per year among those with scores of at least 40 and -0.008 (95% CI, -0.016 to 0.001) m/s per year among those with scores less than 40 (P = .03 for interaction). Multistate models allowing for the competing risk of death demonstrated no effect of intensive treatment on transitions to mobility limitation (hazard ratio, 1.06; 95% CI, 0.92-1.22). Conclusions and Relevance: Among adults 75 years or older in SPRINT, treating to a systolic BP target of less than 120 mm Hg compared with a target of less than 140 mm Hg had no effect on changes in gait speed and was not associated with changes in mobility limitation. Trial Registration: clinicaltrials.gov Identifier: NCT01206062.

Dialytic hemodynamics are associated with changes in gait speed.

INTRODUCTION: Functional impairment and reduced mobility are prevalent in patients on chronic hemodialysis (HD). The impact of HD on physical performance and mobility needs evaluation. METHODS: We measured gait speed in a cohort of chronic HD patients both pre and post an HD session. We collected demographic and laboratory data and dialytic hemodynamic parameters for the HD session. Participants completed the Falls Efficacy Scale International (FES-I) survey to assess concern for falling. We used linear regression analysis to tests for associations between our predictor variables of intra-dialytic hemodynamic change and change in gait speed from pre to post HD (primary outcome) and FES-I score (secondary outcome). FINDINGS: Twenty-eight participants completed the study. The mean (SD) age was 64.0 (10.5) years. The majority were male (71.4%), had hypertension (85.7%) and diabetes (57.1%). The mean (SD) change in gait speed from pre to post dialysis was -0.06 (0.08) m/s. A greater decrease in gait speed was associated with greater decrease in SBP and DBP from pre to post HD (p = 0.02 and p = 0.04, respectively) and greater maximum drop in SBP and DBP during HD (p = 0.01 and p <0.01, respectively). The association between maximum drop in SBP and DBP and gait speed remained significant after adjustment for covariates. There was no association between BP change and FES-I score. DISCUSSION: Our results suggest that HD patients who have greater decrease in BP during HD are at risk for decreased gait speed post HD.

Impact of Drug-Drug and Drug-Disease Interactions on Gait Speed in Community-Dwelling Older Adults.

BACKGROUND: Gait speed decline, an early marker of functional impairment, is a sensitive predictor of adverse health outcomes in older adults. The effect of potentially inappropriate medications, including drug-disease and drug-drug interactions, on gait speed decline is not well known. OBJECTIVE: The aim of this study was to determine if drug interactions impair functional status as measured by gait speed. METHODS: The sample included 2402 older adults with medication and gait speed data from the Health, Aging and Body Composition study. The independent variable was the frequency of drug-disease and/or drug-drug interactions at baseline and 3 additional years. The main outcome was a clinically meaningful gait speed decline of ≥0.1 m/s the year following drug interaction assessment. Adjusted odds ratios and 95 % confidence intervals (CIs) were calculated using multivariate generalized estimating equations for both the overall sample and a sample stratified by gait speed at time of drug interaction assessment. RESULTS: The prevalence of drug-disease and drug-drug interactions ranged from 7.6 to 9.3 and 10.5 to 12.3 %, respectively, with few participants (3.8-5.7 %) having multiple drug interactions. At least 22 % of participants had a gait speed decline of ≥0.1 m/s annually. Drug interactions were not significantly associated with gait speed decline overall or in the stratified sample of fast walkers. There was some evidence, however, that drug interactions increased the risk of gait speed decline among those participants with slower gait speeds, though p values did not reach statistical significance (adjusted odds ratio 1.22; 95 % CIs 0.96-1.56; p = 0.11). Moreover, a marginally significant dose-response relationship was seen with multiple drug interactions and gait speed decline (adjusted odds ratio 1.40; 95 % CIs 0.95-2.04; p = 0.08). CONCLUSIONS: Drug interactions may increase the likelihood of gait speed decline among older adults with evidence of preexisting debility. Future studies should focus on frail elders with less physiological reserve who may be more susceptible to the harms associated with potentially inappropriate medications.