Abstract Background Mitochondrial dysfunction has been proposed as a therapeutic target to improve muscle strength and endurance, but the contribution that mitochondrial dysfunction makes to impaired skeletal muscle performance in older people remains unclear. We studied the relationship between phosphocreatine recovery rate (a measure of skeletal muscle mitochondrial function) and physical performance in older people. Methods We analysed data from the Allopurinol in Functional Impairment (ALFIE) trial. Participants aged 65 and over, who were unable to walk 400 m in six minutes, underwent 31P magnetic resonance spectroscopy of the calf after exercise at baseline and at 20 weeks follow up. The phosphocreatine recovery half-life time (t-half) was derived as a measure of mitochondrial function. Participants also undertook the 6-minute walk distance, the Short Physical Performance Battery test (SPPB), and had muscle mass measured using bio-impedance analysis. Bivariate correlations and multivariable regression analyses were conducted to determine associations between t-half and baseline factors. Results One hundred and seventeen people underwent baseline 31P magnetic resonance spectroscopy, mean age 80.4 years (SD 6.0); 56 (48%) were female. Mean 6-minute walk was 291 m (SD 80) and mean SPPB score was 8.4 (SD 1.9). T-half was significantly correlated with SPPB score (r = 0.22, p = 0.02) but not with 6-minute walk distance (r = 0.10, p = 0.29). In multivariable linear regression, muscle mass and weight, but not t-half, were independently associated with SPPB score and with 6-minute walk distance. The change in t-half between baseline and 20 weeks was not significantly associated with the change in SPPB (r = 0.03, p = 0.79) or with the change in 6-minute walk distance (r = −0.11, p = 0.28). Conclusion Muscle mass, but not phosphocreatine recovery time, was associated with Short Physical Performance Battery score and 6-minute walk distance in this cohort of older people with functional impairment.

Abstract Background Mitochondrial dysfunction is a potential therapeutic target to improve skeletal muscle function, but the contribution of mitochondrial dysfunction to impaired skeletal muscle performance in older people remains unclear. The aim of this analysis was to test the association between measures of skeletal muscle mitochondrial function and physical performance in older people. Methods We analysed data from the Allopurinol in Functional Impairment trial. Participants aged 65 and over, who were unable to walk 400 m in 6 min, underwent 31P magnetic resonance spectroscopy of the calf after exercise at baseline and at 20 weeks follow up. The phosphocreatine recovery half‐life time (t1/2) was derived as a measure of mitochondrial function. Participants undertook the 6‐min walk test and the Short Physical Performance Battery. Muscle mass measured using the Akern 101 bio‐impedance analysis system. Bivariate correlations and multivariable regression analyses were conducted to determine associations between t1/2 and baseline factors. Results One hundred and seventeen participants underwent baseline 31P magnetic resonance spectroscopy, mean age 80.4 years (SD 6.0); 56 (48%) were female. Mean 6‐min walk was 291 m (SD 80), mean SPPB score was 8.4 (SD 1.9); t1/2 correlated significantly with Short Physical Performance Battery score (r = 0.22, P = 0.02) but not with 6‐min walk distance (r = 0.10, P = 0.29). In multivariable linear regression, muscle mass and total body weight, but not t1/2, were independently associated with Short Physical Performance Battery score and with 6‐min walk distance. Change in t1/2 was not significantly associated with change in Short Physical Performance Battery score (r = 0.03, P = 0.79) or with change in 6‐min walk distance (r = −0.11, P = 0.28). Conclusions Muscle mass, but not phosphocreatine recovery time, was consistently associated with Short Physical Performance Battery score and 6‐min walk distance in older people with functional impairment.

BACKGROUND:Allopurinol has vascular antioxidant effects and participates in purinergic signalling within muscle. We tested whether allopurinol could improve skeletal muscle energetics and physical function in older people with impaired physical performance. METHODS:We conducted a randomised, double blind, parallel group, placebo-controlled trial, comparing 20 weeks of allopurinol 600 mg once daily versus placebo. We recruited community-dwelling participants aged 65 and over with baseline 6-min walk distance of <400 m and no contraindications to magnetic resonance imaging scanning. Outcomes were measured at baseline and 20 weeks. The primary outcome was post-exercise phosphocreatine (PCr) recovery rate measured using 31P magnetic resonance spectroscopy of the calf. Secondary outcomes included 6-min walk distance, short physical performance battery (SPPB), lean body mass measured by bioimpedance, endothelial function and quality of life. RESULTS:In total, 124 participants were randomised, mean age 80 (SD 6) years. A total of 59 (48%) were female, baseline 6-min walk distance was 293 m (SD 80 m) and baseline SPPB was 8.5 (SD 2.0). Allopurinol did not significantly improve PCr recovery rate (treatment effect 0.10 units [95% CI, -0.07 to 0.27], P = 0.25). No significant changes were seen in endothelial function, quality of life, lean body mass or SPPB. Allopurinol improved 6-min walk distance (treatment effect 25 m [95% 4-46, P = 0.02]). This was more pronounced in those with high baseline oxidative stress and urate. CONCLUSION:Allopurinol improved 6-min walk distance but not PCr recovery rate in older people with impaired physical function. Antioxidant strategies to improve muscle function for older people may need to be targeted at subgroups with high baseline oxidative stress.

Viewing a real scene or a stereoscopic image (e.g., 3D movies) with both eyes yields a vivid subjective impression of object solidity, tangibility, immersive negative space and sense of realness; something that is not experienced when viewing single pictures of 3D scenes normally with both eyes. This phenomenology, sometimes referred to as stereopsis, is conventionally ascribed to the derivation of depth from the differences in the two eye's images (binocular disparity). Here we report on a pilot study designed to explore if dissociable neural activity associated with the phenomenology of realness can be localized in the cortex. In order to dissociate subjective impression from disparity processing, we capitalized on the finding that the impression of realness associated with stereoscopic viewing can also be generated when viewing a single picture of a 3D scene with one eye through an aperture. Under a blocked fMRI design, subjects viewed intact and scrambled images of natural 3-D objects, and scenes under three viewing conditions: (1) single pictures viewed normally with both eyes (binocular); (2) single pictures viewed with one eye through an aperture (monocular-aperture); and (3) stereoscopic anaglyph images of the same scenes viewed with both eyes (binocular stereopsis). Fixed-effects GLM contrasts aimed at isolating the phenomenology of stereopsis demonstrated a selective recruitment of similar posterior parietal regions for both monocular and binocular stereopsis conditions. Our findings provide preliminary evidence that the cortical processing underlying the subjective impression of realness may be dissociable and distinct from the derivation of depth from disparity.

Arteriosclerosis (arterial stiffening) is associated with future cardiovascular events, with this effect postulated to be due to its effect on cardiac afterload, atherosclerosis (plaque formation) progression or both, but with limited evidence examining these early in disease formation. The aim of the current study is to examine the association between arteriosclerosis, atherosclerosis and ventricular remodelling in a population at low-intermediate cardiovascular risk.

Purpose To quantify the burden and distribution of asymptomatic atherosclerosis in a population with a low to intermediate risk of cardiovascular disease. Materials and Methods Between June 2008 and February 2013, 1528 participants with 10-year risk of cardiovascular disease less than 20% were prospectively enrolled. They underwent whole-body magnetic resonance (MR) angiography at 3.0 T by using a two-injection, four-station acquisition technique. Thirty-one arterial segments were scored according to maximum stenosis. Scores were summed and normalized for the number of assessable arterial segments to provide a standardized atheroma score (SAS). Multiple linear regression was performed to assess effects of risk factors on atheroma burden. Results A total of 1513 participants (577 [37.9%] men; median age, 53.5 years; range, 40-83 years) completed the study protocol. Among 46 903 potentially analyzable segments, 46 601 (99.4%) were interpretable. Among these, 2468 segments (5%) demonstrated stenoses, of which 1649 (3.5%) showed stenosis less than 50% and 484 (1.0%) showed stenosis greater than or equal to 50%. Vascular stenoses were distributed throughout the body with no localized distribution. Seven hundred forty-seven (49.4%) participants had at least one stenotic vessel, and 408 (27.0%) participants had multiple stenotic vessels. At multivariable linear regression, SAS correlated with age (B = 3.4; 95% confidence interval: 2.61, 4.20), heart rate (B = 1.23; 95% confidence interval: 0.51, 1.95), systolic blood pressure (B = 0.02; 95% confidence interval: 0.01, 0.03), smoking status (B = 0.79; 95% confidence interval: 0.44, 1.15), and socioeconomic status (B = -0.06; 95% confidence interval: -0.10, -0.02) (P < .01 for all). Conclusion Whole-body MR angiography identifies early vascular disease at a population level. Although disease prevalence is low on a per-vessel level, vascular disease is common on a per-participant level, even in this low- to intermediate-risk cohort. © RSNA, 2018 Online supplemental material is available for this article.

Introduction Arteriosclerosis (arterial stiffening) and atherosclerosis (plaque formation) are pathophysiological processes afflicting the vasculature, both of which are associated with future cardiovascular events. However the degree to which they overlap or simply co-exist is poorly understood. The aim of the current study is to determine if these two processes are significantly associated with one another. Methods 1651 volunteers with no clinical manifestation of cardiovascular disease and <20% 10-year cardiovascular risk underwent a cardiac MRI and whole body MR angiogram as part of the TASCFORCE study. Systemic arterial stiffness was measured using total arterial compliance (TAC) – calculated as the indexed stroke volume divided by the pulse pressure. Systemic atheroma burden (AB) was calculated by scoring 30 arterial segments within the body based on the degree of stenosis, summating these scores and normalising it to the number of assessable segments. Results 1515 (574 male, 53.8±8.2 years-old) completed the study.?On multiple linear regression age (B=–0.001 (95%CI –?0.002–−0.000), p=0.004), heart rate (B=–0.003 (95%CI –?0.003–−0.002), p<0.001) and blood pressure (B=–0.008 (95%CI –0.009–−0.008), p<0.001) were independently associated with TAC, while age (B=0.061 (95%CI 0.04–0.08), p<0.001), and smoking pack-year history (B=0.003 (95%CI 0.005), p=0.022) were independently associated with AB. TAC and AB?demonstrated a significant correlation with each other (Spearman rho=–0.12, p<0.001), however on multivariable analysis accounting for age, blood pressure, sex, BMI, smoking status and cholesterol no significant association persisted (B=–?0.001 (95%CI –0.004–0.002), p=0.62). Conclusion Systemic arteriosclerosis and atherosclerosis are separate entities with each determined by different risk factors. Future efforts in cardiovascular risk prevention should seek to address both of these pathophysiological entities.

We thank Drs. Stollberger and Finsterer for their interest in our paper on left ventricular noncompaction (LVNC) in which we report that a significant proportion of an asymptomatic healthy population meet current diagnostic criteria [(1)][1]. As they quite rightly state cardiac magnetic resonance

Aims Unrecognized myocardial infarctions (UMIs) have been described in 19-30% of the general population using late gadolinium enhancement (LGE) on cardiac magnetic resonance. However, these studies have focused on an unselected cohort including those with known cardiovascular disease (CVD). The aim of the current study was to ascertain the prevalence of UMIs in a non-high-risk population using magnetic resonance imaging (MRI).Methods and results A total of 5000 volunteers aged.40 years with no history of CVD and a 10-year risk of CVD of,20%, as assessed by the ATP-III risk score, were recruited to the Tayside Screening for Cardiac Events study. Those with a B-type natriuretic peptide (BNP) level greater than their gender-specific median were invited for a whole-body MR angiogram and cardiac MR including LGE assessment. LGE was classed as absent, UMI, or non-specific. A total of 1529 volunteers completed the imaging study; of these, 53 (3.6%) were excluded because of either missing data or inadequate LGE image quality. Ten of the remaining 1476 (0.67%) displayed LGE. Of these, three (0.2%) were consistent with UMI, whereas seven were non-specific occurring in the mid-myocardium (n=4), epicardium (n=1), or right ventricular insertion points (n=2). Those with UMI had a significantly higher BNP [median 116 (range 31-133) vs. 22.6 (5-175) pg/mL, P=0.015], lower ejection fraction [54.6 (36-62) vs. 68.9 (38-89)%, P=0.007], and larger end-systolic volume [36.3 (27-61) vs. 21.7 (5-65) mL/m(2), P=0.014]. Those with non-specific LGE had lower diastolic blood pressure [68 (54-70) vs. 72 (46-98) mmHg, P= 0.013] but no differences in their cardiac function.Conclusion Despite previous reports describing high prevalence of UMI in older populations, in a predominantly middle-aged cohort, those who are of intermediate or low cardiovascular risk have a very low risk of having an unrecognized myocardial infarct.

BACKGROUND:Depression is a disabling disorder that significantly impacts on the interpersonal functioning of individuals. However, little is known about the neural substrates of such difficulties. In the last few years neuroeconomics, which combines imaging with multiplayer behavioural economic paradigms, has been used to study the neural substrates of normal and abnormal interpersonal interactions.METHOD:This study used functional magnetic resonance imaging to investigate neural activity in unmedicated depressed participants (n = 25) and matched healthy controls (n = 25). During scanning, participants played a behavioural economic game, the Prisoner's Dilemma. In this game, the participant and a co-player independently choose either to cooperate or not cooperate with each other.RESULTS:Depressed participants reported higher levels of negative feelings (betrayal, guilt) during the game than did controls. Neural activation was compared between 'imbalanced' events [when one of the players cooperated and the other defected ('CD' and 'DC')] and 'draw' events [when both players either cooperated or defected ('CC' and 'DD')]. Participants preferentially activated the anterior insula and the dorsolateral prefrontal cortex (DLPFC), a region implicated in cognitive control and regulation of emotions. Importantly, compared to controls depressed participants showed reduced activation in the left DLPFC, with the extent of signal reduction correlating with increased self-report feelings of guilt associated with DC outcomes.CONCLUSIONS:Our findings suggest that depression is associated with reduced activation of the DLPFC during social events that involve unreciprocated cooperation. This abnormality may underlie anomalies in cognitive control and top-down regulation of emotions during challenging social exchanges.

Citation for published version (APA): Gandy, S. J., Lambert, M., Belch, J., Cavin, I., Crowe, E., Littleford, R., ... Houston, J. G. (2016). 3T MRI investigation of cardiac left ventricular structure and function in a UK population: The tayside screening for the prevention of cardiac events (TASCFORCE) study. Journal of Magnetic Resonance Imaging, 44(5), 1186-1196. [25267]. https://doi.org/10.1002/jmri.25267

BACKGROUND There is considerable overlap between left ventricular noncompaction (LVNC) and other cardiomyopathies. LVNC has been reported in up to 40% of the general population, raising questions about whether it is a distinct pathological entity, a remodeling epiphenomenon, or merely an anatomical phenotype.OBJECTIVES The authors determined the prevalence and predictors of LVNC in a healthy population using 4 cardiac magnetic resonance imaging diagnostic criteria.METHODS Volunteers >40 years of age (N = 1,651) with no history of cardiovascular disease (CVD), a 10-year risk of CVD < 20%, and a B-type natriuretic peptide level greater than their gender-specific median underwent magnetic resonance imaging scan as part of the TASCFORCE (Tayside Screening for Cardiac Events) study. LVNC ratios were measured on the horizontal and vertical long axis cine sequences. All individuals with a noncompaction ratio of >= 2 underwent short axis systolic and diastolic LVNC ratio measurements, and quantification of noncompacted and compacted myocardial mass ratios. Those who met all 4 criteria were considered to have LVNC.RESULTS Of 1,480 participants analyzed, 219 (14.8%) met >= 1 diagnostic criterion for LVNC, 117 (7.9%) met 2 criteria, 63 (4.3%) met 3 criteria, and 19 (1.3%) met all 4 diagnostic criteria. There was no difference in demographic or allometric measures between those with and without LVNC. Long axis noncompaction ratios were the least specific, with current diagnostic criteria positive in 219 (14.8%), whereas the noncompacted to compacted myocardial mass ratio was the most specific, only being met in 61 (4.4%).CONCLUSIONS A significant proportion of an asymptomatic population free from CVD satisfy all currently used cardiac magnetic resonance imaging diagnostic criteria for LVNC, suggesting that those criteria have poor specificity for LVNC, or that LVNC is an anatomical phenotype rather than a distinct cardiomyopathy. (C) 2016 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Introduction Unrecognised myocardial infarctions (UMIs) have been described in 19–30% of the population using late gadolinium enhancement (LGE). However these studies have focussed on unselected cohorts including those with known cardiovascular disease. The aim of the current study was to ascertain the prevalence of UMIs in a non-high risk population and their physiological significance. Methods 5,000 volunteers >40 years with no history of cardiovascular disease (CVD) and a 10 year risk of CVD of less than 20% were recruited to the Tayside Screening for Cardiac Events (TASCFORCE) study. Those with a BNP level greater than their gender-specific median were invited for a whole-body MR angiogram and cardiac MR including LGE. LGE was classed as absent, UMI, or non-specific. Results 1,529 completed the imaging study with 53 (3.6%) excluded due to missing data or inadequate LGE image quality. 10 of the remaining 1476 (0.67%) displayed LGE. Of these, 3 (0.2%) were consistent with UMI, while 7 were non-specific occurring in the mid-myocardium (n = 4), epicardium (n = 1) or right ventricular insertion points (n = 2). Those with UMI had significantly higher BNP(median 116 (range 31–133) vs 22.6 (5–175) pg/ml, p = 0.015), lower ejection fraction (54.6 (36–62) vs 68.9 (38–89) %, p = 0.007) and larger end systolic volume (36.3 (27–61) vs 21.7 (5–65) ml/m2, p = 0.014). Those with non-specific LGE had lower diastolic blood pressure (68 (54–70) vs 72 (46–98) mmHg, p = 0.013), but no differences in their cardiac function. Conclusion Despite previous reports describing high prevalence of UMI, those who are of low-intermediate cardiovascular risk have a very low prevalence of UMI. LGE typical of UMI is associated with significantly impaired cardiac function, while LGE atypical of UMI has no adverse effect on function.

PurposeTo scan a volunteer population using 3.0T magnetic resonance imaging (MRI). MRI of the left ventricular (LV) structure and function in healthy volunteers has been reported extensively at 1.5T.Materials and MethodsA population of 1528 volunteers was scanned. A standardized approach was taken to acquire steady‐state free precession (SSFP) LV data in the short‐axis plane, and images were quantified using commercial software. Six observers undertook the segmentation analysis.ResultsMean values (±standard deviation, SD) were: ejection fraction (EF) = 69 ± 6%, end diastolic volume index (EDVI) = 71 ± 13 ml/m2, end systolic volume index (ESVI) = 22 ± 7 ml/m2, stroke volume index (SVI) = 49 ± 8 ml/m2, and LV mass index (LVMI) = 55 ± 12 g/m2. The mean EF was slightly larger for females (69%) than for males (68%), but all other variables were smaller for females (EDVI 68v77 ml/m2, ESVI 21v25 ml/m2, SVI 46v52 ml/m2, LVMI 49v64 g/m2, all P < 0.05). The mean LV volume data mostly decreased with each age decade (EDVI males: –2.9 ± 1.3 ml/m2, females: –3.1 ± 0.8 ml/m2; ESVI males: –1.3 ± 0.7 ml/m2, females: –1.7 ± 0.5 ml/m2; SVI males: –1.7 ± 0.9 ml/m2, females: –1.4 ± 0.6 ml/m2; LVMI males: –1.6 ± 1.1 g/m2, females: –0.2 ± 0.6 g/m2) but the mean EF was virtually stable in males (0.6 ± 0.6%) and rose slightly in females (1.2 ± 0.5%) with age.ConclusionLV reference ranges are provided in this population‐based MR study at 3.0T. The variables are similar to those described at 1.5T, including variations with age and gender. These data may help to support future population‐based MR research studies that involve the use of 3.0T MRI scanners. J. Magn. Reson. Imaging 2016;44:1186–1196.

Neural substrates of memory control are engaged when participants encounter unexpected mnemonic stimuli (e.g., a new word when told to expect an old word). The present fMRI study (n = 18) employed the likelihood cueing recognition task to elucidate the role of functional connectivity (fcMRI) networks in supporting memory control processes engaged by these unexpected events. Conventional task-evoked BOLD analyses recovered a memory control network similar to that previously reported, comprising medial prefrontal, lateral prefrontal, and inferior parietal regions. These were split by their differential affiliation to distinct fcMRI networks (“conflict detection” and “confirmatory retrieval” networks). Subsequent ROI analyses clarified the functional significance of this connectivity differentiation, with “conflict” network-affiliated regions specifically sensitive to cue strength, but not to response confidence, and “retrieval” network-affiliated regions showing the opposite pattern. BOLD time course analyses corroborated the segregation of memory control regions into “early” conflict detection and “late” retrieval analysis, with both processes underlying the allocation of memory control. Response specificity and time course findings were generalized beyond task-recruited ROIs to clusters within the large-scale fcMRI networks, suggesting that this connectivity architecture could underlie efficient processing of distinct processes within cognitive tasks. The findings raise important parallels between prevailing theories of memory and cognitive control.

AIM: To evaluate a combined protocol for simultaneous cardiac MRI (CMR) and contrast-enhanced (CE) whole-body MR angiography (WB-MRA) techniques within a single examination.MATERIALS AND METHODS: Asymptomatic volunteers (n = 48) with low-moderate risk of cardiovascular disease (CVD) were recruited. The protocol was divided into four sections: (1) CMR of left ventricle (LV) structure and function; (2) CE-MRA of the head, neck, and thorax followed by the distal lower limbs; (3) CMR LV "late gadolinium enhancement" assessment; and (4) CE-MRA of the abdomen and pelvis followed by the proximal lower limbs. Multiple observers undertook the image analysis.RESULTS: For CMR, the mean ejection fraction (EF) was 67.3 +/- 4.8% and mean left ventricular mass (LVM) was 100.3 +/- 22.8 g. The intra-observer repeatability for EF ranged from 2.1-4.7% and from 9-12 g for LVM. Interobserver repeatability was 8.1% for EF and 19.1 g for LVM. No LV delayed myocardial enhancement was observed. For WB-MRA, some degree of luminal narrowing or stenosis was seen at 3.6% of the vessel segments (involving n = 29 of 48 volunteers) and interobserver radiological opinion was consistent in 96.7% of 1488 vessel segments assessed.CONCLUSION: Combined assessment of WB-MRA and CMR can be undertaken within a single examination on a clinical MRI system. The associated analysis techniques are repeatable and may be suitable for larger-scale cardiovascular MRI studies. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of The Royal College of Radiologists.