A systematic review of the evidence that brain structure is related to muscle structure and their relationship to brain and muscle function in humans over the lifecourse

BACKGROUND: An association between cognition and physical function has been shown to exist but the roles of muscle and brain structure in this relationship are not fully understood. A greater understanding of these relationships may lead to identification of the underlying mechanisms in this important area of research. This systematic review examines the evidence for whether: a) brain structure is related to muscle structure; b) brain structure is related to muscle function; and c) brain function is related to muscle structure in healthy children and adults. METHODS: Medline, Embase, CINAHL and PsycINFO were searched on March 6th 2014. A grey literature search was performed using Google and Google Scholar. Hand searching through citations and references of relevant articles was also undertaken. RESULTS: 53 articles were included in the review; mean age of the subjects ranged from 8.8 to 85.5 years old. There is evidence of a positive association between both whole brain volume and white matter (WM) volume and muscle size. Total grey matter (GM) volume was not associated with muscle size but some areas of regional GM volume were associated with muscle size (right temporal pole and bilateral ventromedial prefrontal cortex). No evidence was found of a relationship between grip strength and whole brain volume however there was some evidence of a positive association with WM volume. Conversely, there is evidence that gait speed is positively associated with whole brain volume; this relationship may be driven by total WM volume or regional GM volumes, specifically the hippocampus. Markers of brain ageing, that is brain atrophy and greater accumulation of white matter hyperintensities (WMH), were associated with grip strength and gait speed. The location of WMH is important for gait speed; periventricular hyperintensities and brainstem WMH are associated with gait speed but subcortical WMH play less of a role. Cognitive function does not appear to be associated with muscle size. CONCLUSION: There is evidence that brain structure is associated with muscle structure and function. Future studies need to follow these interactions longitudinally to understand potential causal relationships

Increased Skeletal Muscle 11bHSD1 mRNA Is Associated with Lower Muscle Strength in Ageing

Abstract Background: Sarcopenia, the loss of muscle mass and function with age, is associated with increased morbidity and mortality. Current understanding of the underlying mechanisms is limited. Glucocorticoids (GC) in excess cause muscle weakness and atrophy. We hypothesized that GC may contribute to sarcopenia through elevated circulating levels or increased glucocorticoid receptor (GR) signaling by increased expression of either GR or the GC-amplifying enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11bHSD1) in muscle

Design and Validation of a Novel Method to Measure Cross-Sectional Area of Neck Muscles Included during Routine MR Brain Volume Imaging

Low muscle mass secondary to disease and ageing is an important cause of excess mortality and morbidity. Many studies include a MR brain scan but no peripheral measure of muscle mass. We developed a technique to measure posterior neck muscle cross-sectional area (CSA) on volumetric MR brain scans enabling brain and muscle size to be measured simultaneously.We performed four studies to develop and test: feasibility, inter-rater reliability, repeatability and external validity. We used T1-weighted MR brain imaging from young and older subjects, obtained on different scanners, and collected mid-thigh MR data.After developing the technique and demonstrating feasibility, we tested it for inter-rater reliability in 40 subjects. Intraclass correlation coefficients (ICC) between raters were 0.99 (95% confidence intervals (CI) 0.98-1.00) for the combined group (trapezius, splenius and semispinalis), 0.92 (CI 0.85-0.96) for obliquus and 0.92 (CI 0.85-0.96) for sternocleidomastoid. The first unrotated principal component explained 72.2% of total neck muscle CSA variance and correlated positively with both right (r = 0.52, p = .001) and left (r = 0.50, p = .002) grip strength. The 14 subjects in the repeatability study had had two MR brain scans on three different scanners. The ICC for between scanner variation for total neck muscle CSA was high at 0.94 (CI 0.86-0.98). The ICCs for within scanner variations were also high, with values of 0.95 (CI 0.86-0.98), 0.97 (CI 0.92-0.99) and 0.96 (CI 0.86-0.99) for the three scanners. The external validity study found a correlation coefficient for total thigh CSA and total neck CSA of 0.88.We present a feasible, valid and reliable method for measuring neck muscle CSA on T1-weighted MR brain scans. Larger studies are needed to validate and apply our technique with subjects differing in age, ethnicity and geographical location

Neck muscle cross-sectional area, brain volume and cognition in healthy older men; A cohort study

BACKGROUND: Two important consequences of the normal ageing process are sarcopenia (the age-related loss of muscle mass and function) and age-related cognitive decline. Existing data support positive relationships between muscle function, cognition and brain structure. However, studies investigating these relationships at older ages are lacking and rarely include a measure of muscle size. Here we test whether neck muscle size is positively associated with cognition and brain structure in older men. METHODS: We studied 51 healthy older men with mean age 73.8 (sd 1.5) years. Neck muscle cross-sectional area (CSA) was measured from T1-weighted MR-brain scans using a validated technique. We measured multiple cognitive domains including verbal and visuospatial memory, executive functioning and estimated prior cognitive ability. Whole brain, ventricular, hippocampal and cerebellar volumes were measured with MRI. General linear models (ANCOVA) were performed. RESULTS: Larger neck muscle CSA was associated with less whole brain atrophy (t = 2.86, p = 0.01, partial eta squared 17%). Neck muscle CSA was not associated with other neuroimaging variables or current cognitive ability. Smaller neck muscle CSA was unexpectedly associated with higher prior cognition (t = −2.12, p < 0.05, partial eta squared 10%). CONCLUSIONS: In healthy older men, preservation of whole brain volume (i.e. less atrophy) is associated with larger muscle size. Longitudinal ageing studies are now required to investigate these relationships further

Increased Skeletal Muscle 11βHSD1 mRNA Is Associated with Lower Muscle Strength in Ageing

Background: Sarcopenia, the loss of muscle mass and function with age, is associated with increased morbidity and mortality. Current understanding of the underlying mechanisms is limited. Glucocorticoids (GC) in excess cause muscle weakness and atrophy. We hypothesized that GC may contribute to sarcopenia through elevated circulating levels or increased glucocorticoid receptor (GR) signaling by increased expression of either GR or the GC-amplifying enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11βHSD1) in muscle. Methods: There were 82 participants; group 1 comprised 33 older men (mean age 70.2years, SD 4.4) and 19 younger men (22.2years, 1.7) and group 2 comprised 16 older men (79.1years, 3.4) and 14 older women (80.1years, 3.7). We measured muscle strength, mid-thigh cross-sectional area, fasting morning plasma cortisol, quadriceps muscle GR and 11βHSD1 mRNA, and urinary glucocorticoid metabolites. Data were analysed using multiple linear regression adjusting for age, gender and body size. Results: Muscle strength and size were not associated with plasma cortisol, total urinary glucocorticoids or the ratio of urinary 5β-tetrahydrocortisol +5α-tetrahydrocortisol to tetrahydrocortisone (an index of systemic 11βHSD activity). Muscle strength was associated with 11βHSD1 mRNA levels (β -0.35, p = 0.04), but GR mRNA levels were not significantly associated with muscle strength or size. Conclusion: Although circulating levels of GC are not associated with muscle strength or size in either gender, increased cortisol generation within muscle by 11βHSD1 may contribute to loss of muscle strength with age, a key component of sarcopenia. Inhibition of 11βHSD1 may have therapeutic potential in sarcopenia

A case report of hepatic and renal dysfunction complicating midgut malrotation in an adult

A 39-year-old man had an unusual presentation of jaundice and acute renal dysfunction complicating midgut malrotation. Diagnosis by computed tomography scan enabled prompt surgery and functional correction of the malrotation, with a full return to normal life

Intra-class correlation coefficients for the second technique trialled in the feasibility study (Study 1).

<p>Intra-class correlation coefficients for the second technique trialled in the feasibility study (Study 1).</p

Figure of the posterior neck muscles and diagram demonstrating how the measurement plane was selected.

<p>A. Non-contrast T1-weighted MR of transverse plane of the neck at mid-infero-superior-C2 level. B. Outline diagram showing the neck muscles whose cross-sectional areas were measured. C. Outline diagram demonstrating how measurement plane is selected with an example C2 height of 42 mm.</p

Diagram summarizing the methods for the four studies.

<p>Diagram summarizing the methods for the four studies.</p