title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Room F2, 7 George Square, Edinburgh EH8 9JZ, UK. a.kilgour@ed.ac.uk.
authors.forename: Alixe H M
authors.initials: AH
authors.lastname: Kilgour
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Todd
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000033:anatomy & histology* / Q000473:pathology / Q000502:physiology*; D005684:Gait / Q000502:physiology; D006801:Humans; D008136:Longevity / Q000502:physiology*; D053580:Muscle Strength / Q000502:physiology*; D018482:Muscle, Skeletal / Q000033:anatomy & histology* / Q000473:pathology / Q000502:physiology*; D009929:Organ Size