Introduction: Bone loss, fractures, and declining physical performance are associated with muscle atrophy and fat infiltration. Muscle structure and composition differences may be apparent between women with and without osteoporosis (OP). Purpose: To: 1) evaluate the effect of a time period spent in supine on magnetic resonance imaging (MRI) measures of muscle size and diffusion properties in young and older women; 2) assess the feasibility of applying three MRI scanning methods to evaluate macrostructural and microstructural properties of leg muscles in older women; and 3) compare musculoskeletal tissue structure and composition between older women with and without OP, and to determine the relationships between bone, muscle, fat, and physical performance. Methods: Sixteen young and older women had their legs scanned with MRI at baseline and after 30 and 60 minutes of supine resting. Feasibility of recruitment, participant tolerance to scanning, and image acquisition and analysis protocols were assessed. Thirty-five moderately active, older women with and without OP underwent MRI and peripheral quantitative computed tomography scanning of the leg and performed physical performance tests. Results: In young and older women, muscle size did not change with time spent supine, but water diffusivity decreased in some muscle regions. It is feasible to perform a single session of three MRI scanning techniques in older women. Women with and without OP had similar musculoskeletal structure that showed fat infiltration is associated with reduced bone strength and slower gait speed. Conclusions: In young and older women, muscle size is unaffected by a period of supine rest, but time spent in supine may modify water diffusivity measures. It is feasible to use a combination of MRI scanning techniques to evaluate leg muscle structure in older women. MRI improves our understanding of the relationships among muscle, fat, bone, and physical performance. / Dissertation / Doctor of Science (PhD)

Falls and their consequences among older people are a serious medical and public health problem. Identifying individuals at risk of falling is therefore a major concern. The purpose of this thesis was to evaluate measurement tools of balance control and their predictive value when screening for fall risk in physically dependent individuals ≥65 years old living in residential care facilities, and physically independent individuals ≥75 years old living in the community. Following baseline assessments falls were monitored during six months in physically dependent individuals based on staff reports, and during one year in physically independent individuals based on self reports. In physically dependent individuals test-retest reliability of the Timed Up&Go test (TUG) was established in relation to cognitive impairment. Absolute reliability measures exposed substantial day-to-day variability in mobility performance at an individual level despite excellent relative reliability (ICC 1.1 >0.90) regardless of cognitive function (MMSE ≥10). Fifty-three percent of the participants fell at least once during follow-up. Staff judgement of their residents’ fall risk had the best prognostic value for ruling in a fall risk in individuals judged with ‘high risk’ (positive Likelihood ratio, LR+ 2.8). Timed, and subjective rating of fall risk (modified Get Up&Go test, GUG-m) were useful for ruling out a high fall risk in individuals with TUG scores <15 seconds (negative LR, LR- 0.1) and GUG-m scores of ‘no fall risk’ (LR- 0.4), however few participants achieved such scores. In physically independent individuals balance control was challenged by dual-task performances. Subsequent dual-task costs in gait (DTC), i.e. the difference between single walking and walking with a simultaneous second task, were registered using an electronic mat. Forty-eight percent of the participants fell at least once during follow-up. A small prognostic guidance for ruling in a high fall risk was found for DTC in mean step width of ≤3.7 mm with a manual task (LR+ 2.3), and a small guidance for ruling out a high fall risk with DTC in mean step width of ≤3.6 mm with a cognitive task (LR- 0.5). In cross-sectional evaluations DTC related to an increased fall risk were associated with: sub-maximal physical performance stance scores (Odds Ratio, OR, 3.2 to 3.8), lower self-reported balance confidence (OR 2.6), higher activity avoidance (OR 2.1), mobility disability (OR 4.0), and cautious walking out-door (OR 3.0). However, these other measures of physical function failed to provide any guidance to fall risk in this population of seemingly able older persons. In conclusion – Fall risk assessments may guide clinicians in two directions, either in ruling in or in ruling out a high fall risk. A single cut-off score, however, does not necessarily give guidance in both directions. Staff experienced knowledge is superior to a single assessment of mobility performance for ruling in a high fall risk. Clinicians need to consider the day-to-day variability in mobility when interpreting the TUG score of a physically dependent individual. DTC of gait can, depending on the type of secondary task, indicate a functional limitation related to an increased fall risk or a flexible capacity related to a decreased fall risk. DTC in mean step width seems to be a valid measure of balance control in physically independent older people and may be a valuable part of the physical examination of balance and gait when screening for fall risk as other measures of balance control may fail to provide any guidance of fall risk in this population.

Decreased skeletal muscle function (MF) is ubiquitous in hemodialysis (HD) patients and linked to functional decline. Serum vitamin D (25-OHD) and habitual physical activity (PA) are decreased in HD and linked to reduced MF in other populations. The associations between 25-OHD, PA, and MF were investigated in 81 stable HD patients. PA intensity was quantified using accelerometery, MF using handgrip strength dynamometery, 25-OHD via serum measures, and dietary and supplementation of vitamin D intake via three-day food records. MF correlated with PA (r =0.411, p = 0.003) when controlled for body mass (BM) and with 25-OHD (r =0.298, p = 0.023) when controlled for BM, age, and sex. Both MF (r=0.285, p=0.025) and 25-OHD (r=0.314, p=0.005) correlated with vitamin D supplementation. MF remained correlated with supplementation after controlling for 25-OHD (r=0.269, p=0.037). These findings should be further explored in interventional studies to assess how their manipulation influences MF in HD.

Decreased skeletal muscle function (MF) is ubiquitous in hemodialysis (HD) patients and linked to functional decline. Serum vitamin D (25-OHD) and habitual physical activity (PA) are decreased in HD and linked to reduced MF in other populations. The associations between 25-OHD, PA, and MF were investigated in 81 stable HD patients. PA intensity was quantified using accelerometery, MF using handgrip strength dynamometery, 25-OHD via serum measures, and dietary and supplementation of vitamin D intake via three-day food records. MF correlated with PA (r =0.411, p = 0.003) when controlled for body mass (BM) and with 25-OHD (r =0.298, p = 0.023) when controlled for BM, age, and sex. Both MF (r=0.285, p=0.025) and 25-OHD (r=0.314, p=0.005) correlated with vitamin D supplementation. MF remained correlated with supplementation after controlling for 25-OHD (r=0.269, p=0.037). These findings should be further explored in interventional studies to assess how their manipulation influences MF in HD.

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<p>Hintergrund: Es gibt nur begrenzte Kenntnisse über Surrogat-Parameter für eine Verschlechterung der körperlichen Funktionsfähigkeit (SF-36) im Verlauf bei Patienten mit diastolischer Dysfunktion/Herzinsuffizienz bzw. mit Risikofaktoren hierfür. Diese Arbeit untersuchte die Assoziation neurohumoraler Aktivierung mit physischer Lebensqualität (SF-36) im Ein-Jahres-Verlauf.</p> <p> Methoden: In der bevölkerungsbasierten Diast-CHF-Studie wurden n=1937 Patienten mit Risikofaktoren für eine diastolische Herzinsuffizienz oder bereits diagnostizierter Herzinsuffizienz eingeschlossen. Für die Fragestellung wurden n=855 Patienten analysiert (Einschlusskriterien: LVEF≥50%, vorhandene Daten für LQ zu beiden Messzeitpunkten im Ein-Jahres-Verlauf (SF-36)). Alle Patienten wurden dichotomisiert in eine Gruppe mit unveränderter/verbesserter (PhF+) vs. verschlechterter körperlicher Funktionsfähigkeit (PhF-) nach einem Jahr (1-FU) im Vergleich zu den erhobenen Baseline-Werten. Verschlechterte körperliche Lebensqualität (PhF-) wurde definiert als eine Verschlechterung um mindestens eine halbe Standardabweichung gegenüber den Werten aus der Baseline. Bei allen Patienten wurden Blutentnahmen, detaillierte echokardiographische Untersuchungen sowie ein 6-Minuten-Gehtest (6-MWD) durchgeführt.</p><p> Ergebnisse: Die analysierte Population (n=855) setzte sich aus n=718 (84%) mit PhF+ sowie n=137 (16%) mit PhF- zusammen. PhF+/PhF-: Alter: 65,6±7,3/69,4±7,7 (p<0,001), BMI: 28,6±4,6/30,4±5,1 (p<0,001), LVEF: 61,6±6,2/61,9±5,8% (p=0,646), 6-MWD: 524,4±109,5/486,0±86,8 (p<0,001), NT-proBNP: 129,8/220,3 (p=0,030), MR-proADM: 0,58/0,69 (p=0,001), MR-proANP: 95,1/121,5 (p=0,009), CT-proET1: 54,6/62,4 (p=0.001). E/é: 9,8/10,9 (p=0,003), LAVI: 23,9/26,3 (p=0,007) und LVMI: 115,1/120,2 (p=0,045). Aus den Ergebnissen der linearen und logistischen Regression ging hervor, dass insbesondere das MR-proADM eine signifikante Assoziation zum Ein-Jahres-Verlauf körperlichen Funktionsfähigkeit (p<0,001) zeigte. Diese Assoziation war unabhängig von Parametern wie Alter, BMI und E/é.</p><p> Fazit: Neurohormone scheinen sich als Surrogat-Parameter für eine Verschlechterung der physischen Lebensqualität im Verlauf bei Patienten mit diastolischer Dysfunktion/Herzinsuffizienz oder kardiovaskulären Risikofaktoren hierfür zu eignen.

Although the female menopause has been extensively characterized as a well-defined symptomatic state of oestrogen deficiency, which responds relatively well to oestrogen replacement therapy, the symptomatic state of androgen deficiency in men is poorly defined and uncertainty exists whether it responds to testosterone replacement. It has been proposed that hypothalamic-pituitary-testicular (HPT)-axis function (responsible for the production of androgens) and regulation could be viewed as a ‘barometer’ of health status in older men and that potential alterations in HPT-axis function and regulation reflect subclinical and clinical deficits in function and health, which may result in an aged phenotype of human health and disease in older men. The HPT-axis constitutes a well-defined, tractable, clinically-relevant, biological system, which may permit insight into the mechanisms underlying the expression of ageing-related phenotypes of human health and disease. By using a different lens – such as the genetic background; the compensatory responses within the HPT-axis; the syndromes of androgen deficiency; the ethnic background of an individual or the life course trajectory of function and health from conception into older age – to magnify potential dysregulation in the HPT-axis will it be possible to visualize and understand the phenotypic expression of human male ageing as a gradient of functional and health outcomes. This will allow for a better understanding of the physiological mechanics underlying symptomatic expression of dysregulation in the HPT-axis.