Starr, John

Walker, Brian

MacLullich, Alasdair

Kilgour, Alexandra Helen Middleton

Medical Research Council (MRC)

2016-02-26T15:48:58Z

2016-02-26T15:48:58Z

2015-06-29

Background Sarcopenia and age-related cognitive decline (ARCD) are important age-related conditions which significantly impact upon the quality of life of older adults. ARCD is a well-established research area, whereas sarcopenia is a relatively new field. Research into the inter-relationships between them and possible common underlying mechanistic processes is lacking. Methods Several research techniques were used: a large systematic review; the development of an image analysis technique to measure neck muscle size on volumetric MR brain scans; the subsequent use of the technique in elderly cohort studies; statistical modelling to investigate the role of glucocorticoids in sarcopenia; and an invasive clinical study to develop a novel technique to measure the activity of 11beta-hydroxysteroid dehydrogenase (11βHSD1) in the human brain in vivo. Results I consistently found a relationship between: some measures of brain structure and muscle size; markers of brain structure and muscle function, mostly grip strength and gait speed; and cognition and muscle function. However, I found no relationship between current cognition and muscle size in any of the above studies. Cortisol was identified as a possible explanatory factor in the relationship between both cognition and brain volume with gait speed. I found an association between markers of immunosenescence and sarcopenia (neck muscle CSA and grip strength) and an association between expression of the cortisol amplifying enzyme 11βHSD1 and quadriceps strength. I developed a technique to measure 11βHSD1 activity across the human brain, which found that the amount of cortisol produced within the brain was not detectable and highlighted the asymmetries within the cerebrovascular venous system. Conclusions Further longitudinal studies looking at the association between sarcopenia and ARCD are now required to investigate these important relationships further and hopefully this will lead to improved therapeutic options.

http://hdl.handle.net/1842/14231

en

The University of Edinburgh

Design and validation of a novel method to measure cross-sectional area of neck muscles included during routine MR brain volume imaging. Kilgour AH, Subedi D, Gray CD, Deary IJ, Lawrie SM, Wardlaw JM, Starr JM. PLoS One. 2012;7(4):e34444.

Neck muscle cross-sectional area, brain volume and cognition in healthy older men: a cohort study. Kilgour AH, Ferguson KJ, Gray CD, Deary IJ, Wardlaw JM, MacLullich AM, Starr JM. BMC Geriatrics. 2013 Feb 28;13:20.

Seropositivity for CMV and IL-6 levels are associated with grip strength and muscle size in the elderly. Kilgour AH, Firth C, Harrison R, Moss P, Bastin ME, Wardlaw JM, Deary IJ, Starr JM. Immunity and Ageing. 2013 Aug 13;10(1):33.

Increased skeletal muscle 11βHSD1 mRNA is associated with lower muscle strength in ageing. Kilgour AH, Gallagher IJ, MacLullich AM, Andrew R, Gray CD, Hyde P, Wackerhage H, Husi H, Ross JA, Starr JM, Chapman KE, Fearon KC, Walker BR, Greig CA. PLoS One. 2013 Dec 31;8(12):e84057.

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. Kilgour AH, Todd OM, Starr JM. BMC Geriatr. 2014 Jul 10;14:85.

11beta-Hydroxysteroid dehydrogenase activity in brain does not contribute to systemic interconversion of cortisol and cortisone in healthy men. Kilgour AH, Semple S, Marshall I, Andrews P, Andrew R, Walker BR. Journal of Clinical Endocrinology and Metabolism. 2015 Feb;100(2):483-489.

Sarcopenia

age-related cognitive decline

glucocorticoids

Sarcopenia and cognitive ageing: investigating their interrelationship, biological correlates and the role of glucocorticoids

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy