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Associations Between Walking Pace, APOE-ε4 Genotype, and Brain Health in Middle-Aged to Older Adults.

PURPOSE: This study aimed to investigate whether self-reported walking pace (a marker of physical function) and the presence of APOE-&#x3b5;4 allele interact to modify brain health outcomes. METHODS: We used data from a prospective cohort study of middle-aged to older adults from the UK Biobank who self-reported walking pace (slow or steady-to-brisk) and who were initially free of dementia ( n = 415,110). Incident all-cause dementia was obtained from hospital and death registry records, and structural brain volumes (right and left hippocampus volumes, total gray matter volume, and volume of white matter hyperintensities) were measured from a subset of participants ( n = 33,113). Cox proportional hazard models and generalized linear models were used to assess associations between exposures and outcomes. RESULTS: Slow walking pace and the presence of APOE-&#x3b5;4 allele were associated with increased dementia risk (HR = 1.79 [95% CI = 1.66-1.93], P < 0.001; HR = 3.06 [2.90-3.23], P < 0.001, respectively), and there was an interaction between these associations, indicating that the association of walking pace with dementia risk is modified by APOE-&#x3b5;4 status (reference group: HR Steady-Brisk/APOE-&#x3b5;4- = 1; HR Slow/APOE-&#x3b5;4- = 2.03 [1.84-2.25], P < 0.001; HR Steady-Brisk/APOE-&#x3b5;4+ = 3.21 [3.02-3.41], P < 0.001; HR Slow/APOE-&#x3b5;4+ = 4.99 [4.48-5.58], P < 0.001). Slow self-reported walking pace was associated with worse brain volume outcomes, and these associations were not modified by APOE-&#x3b5;4 genotype. CONCLUSIONS: These results suggest walking pace and APOE-&#x3b5;4 status independently influence brain volume outcomes, but both factors independently and jointly contribute to increased dementia risk. Individuals with both risk factors (slow walking pace and APOE-&#x3b5;4 allele) show the strongest associations with dementia risk.

Self Report

The self-selected walking pace test and beta blockade.

The self-selected walking pace test is a safe, simple and inexpensive test to measure an individual's perception of walking speed and is more strongly related to maximal oxygen uptake than to age. This study was carried out to determine whether beta blockade, which commonly causes fatigue, would affect the test. Twenty-three clinically healthy men with a mean age of 43 years completed the test both on and off 80 mg long-acting oxprenolol daily, a beta blocking drug with partial agonist activity. The men walked 80 m at three self-selected speeds (rather slow, normal and rather fast). There was a significant reduction in heart rate on the drug. The walking speed at the three paces on and off medication were 1.08 ms-1 and 1.07 ms-1 (slow), 1.32 ms-1 and 1.33 ms-1 (normal) and 1.63 ms-1 and 1.61 ms-1 (fast). None of these differences reached statistical significance. The stride length also did not change. It is concluded that beta blocking medication does not interfere with the self-selected walking pace test.

Adrenergic beta-Antagonists

Symptom-limited, self-paced walking in the assessment of cardiovascular disease in patients with and without heart failure: the predictive value of clinical, anthropometric, echocardiographic and ergonometric parameters.

The assessment of functional capacity in heart disease remains problematic, and it is unclear whether maximal exercise testing is physiologically reflective of the activities of daily living or the quality of life. We therefore employed a symptom-limited, self-paced walking protocol to assess the physical conditions of 41 Nigerian cardiac patients, with and without heart failure. The walking time, walking speed and distance as well as the energy expenditure (Kcal.min-1) were markedly reduced (P less than 0.001) in patients with heart failure (n = 26) compared to the cardiac patients not in failure (n = 15). The double product corrected for exercise time (an index of myocardial oxygen use) was, however, significantly higher (P less than 0.001) in the group with heart failure. Using multiple regression analysis, the parameters of self-paced walking capacity (distance, walking time, and speed) could reliably be predicted (r2 greater than 0.9) from age, body surface area, energy expenditure, and echocardiographic left ventricular dimension in the patients without heart failure. The presence of heart failure appeared to weaken the predictability of the regressions. A significant correlation was obtained between the self paced exercise time and the Bruce protocol treadmill time (r2 = 0.91, P = 0.004) in a subgroup of the patients with heart failure. Thus, the self-paced walking test is sensitive to changes in congestive heart failure and the exercise capacity can be predicted from age and biophysical parameters. The wider clinical usage of this modality, especially in frail patients, is hereby recommended.

Adult

Self-paced walking as a method for exercise testing in elderly and young men.

1. An exercise test has been developed which is suitable for elderly or frail subjects. It is based on free walking at three different speeds on a level indoor course of 256m. The subject sets his own pace in accord with simple instructions. 2. Twenty-four elderly men and ten young men took part in the study. 3. The time and number of paces taken to cover two sections of 100m within the course were used to establish that the subjects walked steadily. Walking speed, pace frequency and stride length were then calculated. 4. Heart rate was obtained with body-borne tape recorders and related to the walking speed. The heart rate at a standard walking speed could then be obtained by interpolation. This is an assessment of the cardiovascular response to exercise (physical condition). The variation on repeating the test was +/-5 per cent and there was no significant difference between the two age groups. 5. The assessment was found to correlate moderately well with a conventional assessment of physical condition based on oxygen uptake from tests on a bicycle ergometer. 6. The test could also be used as a performance index since walking speed was characteristic for the subject. The younger group walked significantly faster than the older group. As a performance index the test is therefor sensitive to age differences.

Adult

A self paced treadmill walking test for breathless patients.

A treadmill exercise test is described that retains the advantages of self paced walking but allows the measurement of cardiorespiratory variables. A horizontal treadmill was modified to allow patients to control their own speed. During exercise continuous measurements of speed, distance, heart rate, arterial oxygen saturation, and stride length were made and subjective assessments of breathlessness were recorded on a visual analogue scale. Ten men with severe chronic obstructive lung disease performed a 12 minute corridor walk and a self paced 12 minute treadmill walk on the same day and repeat treadmill walks on different days. Six of them performed three walks or more. Six patients had ventilatory measurements during treadmill exercise. There was no significant difference (p greater than 0.1) in the distance covered during corridor and treadmill walks, and distances on the treadmill were repeatable after the first walk. Use of a mouthpiece significantly reduced the distance covered on the treadmill. The self paced treadmill walk is a simple repeatable test and has advantages over both a corridor walking test and standard progressive tests for assessment of breathless patients.

Aged

Energy cost of walking at a fixed pace and self-paced before, during, and after pregnancy.

Body weight, basal metabolic rate (BMR), and treadmill metabolic rate (TMR) (3.9 km/h, no elevation) were measured in 39 women at 12, 24, and 36 wk gestation and at 9 wk postpartum. Prepregnancy measurements were also made on 15 of the women. TMR at 36 wk (3.65 +/- 0.50 kcal/min) was significantly higher than at 24 wk (3.38 +/- 0.43 kcal/min) or at 9 wk postpartum (3.38 +/- 0.43 kcal/min). Net energy cost (TMR minus BMR) at 36 wk gestation (2.42 +/- 0.40 kcal/min) was not different from prepregnancy or postpartum values but was significantly higher than at 12 wk (2.28 +/- 0.39 kcal/min) and 24 wk (2.28 +/- 0.37 kcal/min) gestation. In eight women the energy cost of self-paced walking on a treadmill was measured. The absolute and net energy cost decreased sharply from 6 to 12 wk gestation (by 8% and 11%, respectively) but remained unchanged afterwards. The data suggest that in the energy requirements for pregnant women no additional allowance need be made for physical activity, even if a woman's activity pattern includes a substantial amount of externally paced work.

Energy Metabolism

Age-related changes in speed of walking.

Self-paced walking was used as a measure of the neuromuscular slowing observed with aging. The effects of age on the choice of speed of walking, stride length, and step frequency were described for 289 males and 149 females aged 19 to 102 yr. These subjects were asked to walk at three self-selected paces (slow, normal, and fast) over an 80-m indoor course. Sixty-two years coincided with an accelerated decline in speed of walking. Before 62 yr, there was a 1 to 2% per decade decline in normal walking speed. After 63 yr, females showed a 12.4% per decade decrease and males showed a 16.1% per decade decrease. The eldest group (63 yr and older) had a significantly slower speed of walking and smaller step length than the younger groups (19 to 39 and 40 to 62 yr) for all paces. Heart rate at the three paces was not changed across age. In a multiple regression analysis, the only significant independent variable for walking speed at all three paces was (age), which accounted for 19 to 38% of the variance. When the population was divided into two age ranges (19 to 62 and 63 to 102 yr), walking speed was associated with height before 62 yr and with height and age after 62 yr.

Adult

Disentangling the association between chronic pain and sarcopenia-related traits: A bidirectional Mendelian randomization study.

ObjectiveThis study aimed to investigate the potential causal relationships between chronic pain and three key sarcopenia-related quantitative traits: (a) hand grip strength; (b) usual walking pace; and (c) appendicular lean mass, using bidirectional two-sample Mendelian randomization.MethodsWe conducted bidirectional two-sample Mendelian randomization using summary-level data from large-scale genome-wide association studies to assess the genetically predicted associations between chronic pain, including multisite chronic pain and chronic widespread musculoskeletal pain, and the aforementioned sarcopenia-related traits.ResultsMendelian randomization revealed that multisite chronic pain was significantly associated with an increased risk of low hand grip strength (odds ratio = 1.70; p&#x2009;<&#x2009;0.001) and decreased usual walking pace (odds ratio = 0.81; p&#x2009;<&#x2009;0.001); chronic widespread musculoskeletal pain was also significantly associated with decreased usual walking pace (odds ratio = 0.15; p&#x2009;<&#x2009;0.001). Additionally, higher left hand grip strength was significantly associated with a lower risk of multisite chronic pain (odds ratio = 0.90; p<&#x2009;0.001) and chronic widespread musculoskeletal pain (odds ratio = 0.99; p&#x2009;=&#x2009;0.002); higher right hand grip strength was significantly associated with a lower risk of multisite chronic pain (odds ratio = 0.91; p&#x2009;=&#x2009;0.002); and higher usual walking pace was significantly associated with a lower risk of multisite chronic pain (odds ratio = 0.49; p&#x2009;<&#x2009;0.001) and chronic widespread musculoskeletal pain (odds ratio = 0.92; p&#x2009;<&#x2009;0.001). No significant causal associations were detected for appendicular lean mass in either direction (all p&#x2009;>&#x2009;0.05).ConclusionThis study provides genetic evidence supporting potential causal links between chronic pain and key phenotypic components of sarcopenia.

Humans

A bi-directional Mendelian randomization study of&#xa0;sarcopenia-related traits and&#xa0;renal function.

The association between sarcopenia and renal function has been reported in observational studies; however, the directionality and potential causal nature of these associations remain uncertain. We assessed whether genetically predicted sarcopenia-related traits are associated with renal function and vice versa using bidirectional Mendelian randomization (MR). We conducted a bidirectional two-sample MR analysis using publicly available European-ancestry GWAS summary statistics for appendicular lean mass (ALM), hand-grip strength (left and right), and walking pace, and for renal function (cystatin C-based estimated glomerular filtration rate [eGFRcystatin C] and urinary albumin excretion [UAE]). Causal estimates were primarily obtained using inverse-variance weighted (IVW) models, complemented by sensitivity analyses (MR-Egger intercept, weighted median/mode, MR-PRESSO, Radial MR, and leave-one-out). In forward MR, genetically predicted walking pace was positively associated with eGFRcystatin C. Genetically predicted ALM and grip strength (right and left) were inversely associated with UAE. In reverse MR, genetically predicted UAE was inversely associated with ALM and right-hand grip strength. Estimates were broadly consistent across sensitivity analyses, and outlier-robust analyses (MR-PRESSO/Radial MR) yielded similar results. These findings provide genetic evidence consistent with bidirectional relationships between sarcopenia-related traits and renal function (particularly UAE), under standard MR assumptions. Given potential limitations (e.g., heterogeneity, pleiotropy, and possible sample overlap), the results should be interpreted cautiously and complemented by other lines of evidence.

Humans

Polygenic Associations between Motor Behaviour, Neuromotor Traits, and Active Music Engagement in Four Cohorts.

Phenotypic investigations have shown that actively engaging with music, i.e., playing a musical instrument or singing may be protective of motor decline in aging. For example, music training associated with enhanced sensorimotor skills accompanied by changes in brain structure and function. Although it is possible that the benefits of active music engagement "transfer" to benefits in the motor domain, it is also possible that the genetic architecture of motor behaviour and the motor system structure may influence active music engagement. This study investigated whether polygenic scores (PGS) for five behavioural motor traits, 12 neuromotor structural brain traits, and seven rates of change in brain structure traits trained from existing discovery genome-wide association studies (GWAS) predict active music engagement outcomes in four independent cohorts of unrelated individuals of European ancestry: the Canadian Longitudinal Study on Aging (CLSA; N=22,198), Wisconsin Longitudinal Study (WLS; N=4,605), Vanderbilt's BioVU Repository (BioVU; N=6,150), and Vanderbilt's Online Musicality study (OM; N=1,559). Results were meta-analyzed for each PGS main effect across outcomes and cohorts, revealing that PGS for a faster walking pace was associated with higher amounts of active music engagement. Within CLSA, a higher PGS for walking pace was associated with greater odds of engaging with music. Findings suggest a shared genetic architecture between motor function and active music engagement. Future intervention-based research should consider the genetic underpinnings of motor behavior when evaluating the effects of music engagement on motor function across the lifespan.

BioVU

The physiological cost of carrying light and heavy loads.

Nine subjects walked on a treadmill with load weights equal to 10% and 40% of body weight carried on the back. Although the speed of the treadmill was selected so that the measured oxygen consumption (VO2) was the same for both load conditions, the heavier load placed an extra strain on the cardiopulmonary system and was perceived by all subjects as harder work than the lighter load. When the subjects worked at their own pace, walking on a level road or climbing stairs with load weights equal to 10% and 40% of body weight, they compensated for the heavier load by decreasing walking speed or climbing rate. Although the energy costs calculated from walking speed, body and load weight for self-paced walking and the external work of stair climbing were the same for both load conditions, the heavier load was again perceived as harder work. These findings are discussed as they relate to the definition of acceptable load weights.

Adult

The contribution of psychological features to the symptoms of treated hypertensive patients.

Twenty-seven symptoms of 859 treated hypertensive patients were evaluated using a self-administered questionnaire and correlated with the depression (DEP), free-floating anxiety (FFA), phobic anxiety (PHO), obsessionality (OBS) and extraversion (HYS) scores of the Middlesex Hospital Questionnaire. The psychological features were associated with 24 of the 27 symptoms, and the extent to which these measurements determined the presence of a symptom was calculated. DEP and FFA were correlated with most of the symptoms, PHO with weak limbs, blurred vision, slow walking pace, nocturia and a lessened interest in sex. HYS was positively associated with the frequency of sexual intercourse in men and negatively with complaints of dyspnoea, tingling in the limbs and a slow walking pace. OBS was only associated with diarrhoea.

Aged

Genetically Predicted Muscle Mass and Function in Relation to Deep Vein Thrombosis: A Two-step Mendelian Randomization Study Highlighting the Mediating Role of BMI.

BackgroundSarcopenia is observationally linked to venous thromboembolism, but the causal architecture and underlying biological pathways remain largely unclear. This study investigated the causal effects of sarcopenia-related traits on lower extremity deep vein thrombosis (DVT) and quantified potential mediating mechanisms.MethodsWe performed two-sample bidirectional Mendelian randomization (MR) and two-step mediation MR using large-scale GWAS data from UK Biobank, EMBL-EBI, and FinnGen. Exposures included appendicular lean mass (ALM), leg fat-free mass (LFM), hand grip strength, and walking pace. Eighteen candidate mediators were screened for indirect pathways.ResultsGenetically predicted higher ALM was significantly associated with increased DVT risk (FinnGen: OR = 1.288, 95% CI: 1.215-1.365, P < 0.001). Similar positive associations were observed for LFM (OR = 1.920-1.954, P < 0.001). By contrast, muscle functional traits - grip strength and walking pace - demonstrated no consistent causal effects. Reverse MR confirmed a unidirectional relationship. Body mass index (BMI) emerged as a pivotal mediator, accounting for 7.58% - 10.50% of the ALM-DVT effect and 52.74% - 62.73% of the LFM-DVT effect. Notably, the independent effect of ALM was largely attenuated after adjusting for metabolic confounders in multivariable MR.ConclusionGenetic predisposition to high muscle mass, rather than functional strength, increases DVT risk. This relationship appears to be significantly driven by metabolic adiposity, suggesting that the "muscle-vascular-coagulation" interaction is partly explained by body-size-related metabolic burden. Risk stratification should integrate muscle mass evaluation with comprehensive metabolic health assessments.

Humans

Usefulness of a branching treadmill protocol for evaluation of cardiac functional capacity.

A branching treadmill protocol was designed to measure functional capacity in patients with low work capacity and varying ability to walk at speeds used in traditional protocols. A comfortable walking pace is first selected (2.0 to 3.5 mph, 0.25 mph increments) and the workload is then increased every 2 minutes in 1 MET increments (a multiple of the resting oxygen uptake [1 MET = 3.5 ml O2/kg/min]) by adjusting grade. Nine trained (maximal MET = 7.6 +/- 1.6, mean +/- standard deviation) male subjects (age 59 +/- 7 years) with previous myocardial infarction and 9 trained (maximal MET = 11.7 +/- 2.5) male control subjects (age 56 +/- 8 years) completed submaximal and maximal workloads without handrail support. The measured oxygen consumption, volume of oxygen in ml/kg/min (VO2), was compared with the predicted VO2 cost of treadmill walking calculated from speed and grade. A linear regression analysis of predicted versus measured VO2 was performed. There were no significant differences between myocardial infarction and control regression lines. Therefore, a simplified prediction equation for estimated VO2 in myocardial infarction and control subjects is proposed. Overall VO2 prediction = 1.61 + 0.99 x. The main advantage of the branching protocol format is the selection of a stable, brisk walking pace compatible with age and gait, which may improve mechanical efficiency through impedance matching. The protocol is adaptable enough in design so that most patients can complete the exercise test without use of handrails, which is essential for an accurate estimate of VO2 from treadmill speed and grade.

Aged

Walking while using a sensory tactile feedback system: potential use with a functional electrical stimulation orthosis.

A major limitation in the utilization of a functional electrical stimulation (FES) orthosis for routine, daily standing and walking of the spinal-cord-injured person is that visual monitoring is required to maintain balance and the walking pace. For standing and walking to be continuous and automatic with such an orthosis, a closed-loop sensory feedback system is proposed and evaluated; it provides vibrotactile feedback as a substitute to one's own visual sensation. Eight blindfolded experimental subjects were utilized as 'imitators' to interpret the footfalls of a second person (the pace setter). The experimental objective was to test the hypothesis that sufficient information could be transferred by way of the sensory (tactile) feedback system to the 'imitator' and to determine effectively foot position and anticipate the next step of the pacesetter. Quantitative analysis evaluated the effect of three different levels of training, under two different levels of cognitive load. The results disclosed a significant improvement in subject performance at the higher training levels compared with the 'no training' level (P = 0.01). Neither the cognitive load nor the interaction of training and cognitive load altered significantly the effect of training on subject performance. The experimental hypothesis is therefore satisfied that sufficient information was indeed transferred using the apparatus described. Such information (when utilized in conjunction with a thorough training programme) could be used in a practical sense by a paraplegic individual to interpret his own foot steps. Through continued use and training, it is likely that this information could become subconscious and automatic.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult