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There is mounting evidence of a positive association between musical training and cognitive ability in older age (often defined as 60 years or older); for reviews see Chan and Alain, (2020); Roman-Caballero et al., (2018); Schneider et al., (2018). This observation has led researchers to suggest that musical training (which can include formal and informal musical training, practice and performance) might provide an effective means of supporting cognitive health in later life. However, little is currently known regarding the neurobiological mechanisms that might underlie behavioural associations between musical training and cognitive function in older age. The relationship between brain structure and cognitive ability remains an active topic of investigation. Currently, it is known that cognitive ability is correlated with multiple measures of global brain properties including total brain volume, grey matter volume, normal appearing white matter volume and white matter tract integrity. There are also regional differences in the magnitude of these correlations. A recent study with 29,004 middle-aged and older adult participants reported that the strongest regional correlates of cognitive ability were volumes of the frontal, insula, anterior and medial temporal, lateral occipital and paracingulate cortices, the volume of subcortical structures (particularly thalamic volume), and the white matter microstructure of thalamic and association fibres, and of the forceps minor (Cox et al., 2019). Brain resilience to age related cognitive decline could reflect at least two different processes: brain reserve and brain maintenance (Stern et al., 2020). The former is described as a passive process whereby individuals with a higher brain capacity (i.e. larger brains with more synapses and neurons) can withstand more neuronal loss and pathology before reaching a clinical threshold for cognitive impairment. Brain maintenance, on the other hand, describes a slower rate of age-related brain changes or slower development of pathology over time (Nyberg et al., 2012; Stern, 2002; Stern et al., 2020). These global measures have been found to correlate positively, and reliably with cognitive ability in older age (Cox et al., 2019; Penke et al., 2010; Royle et al., 2013) and are commonly treated as markers of brain reserve. Less decline in these brain tissue volumes, and slower progression of white matter hyperintensities reflect brain maintenance and there is some evidence that this slower pattern of change is moderately, positively correlated with healthier cognitive ageing (Cox et al., 2021; Nyberg et al., 2012; Ritchie et al., 2015). Cross-sectional neuroimaging studies with samples of adults have documented structural brain differences between musically-naïve and musically-trained individuals. This latter group includes amateur musicians (often defined as individuals who make music regularly but not as part of their profession or education) and professional musicians (often defined as performing artists, music students and music teachers). Findings from such studies suggest that (amateur and professional) musicians’ brains are characterised by structural differences across a widely distributed network of brain regions including those supporting musically-relevant sensorimotor and auditory processes (e.g. de Manzano & Ullén, 2018; Gaser & Schlaug, 2003; Habibi et al., 2018; P. Schneider et al., 2002) and higher-order cognitive functions (e.g. Bermudez et al., 2009; Gaser & Schlaug, 2003; James et al., 2014). In a recent meta-analysis of MRI studies with adult musicians and non-musicians, Criscuolo et al. (2021) found that musicians had greater grey matter volume in the superior temporal gyrus, postcentral gyrus, supramarginal gyrus, insula, hippocampus, thalamus, cerebellum and brainstem; and greater white matter volume of the internal capsule bundle, corona radiata, corpus callosum, optic radiation and anterior thalamic radiations (note that this analysis did not control for the potentially confounding effects of participant characteristics). It is possible that such structural brain differences are maintained in older age and, potentially, contribute to brain reserve or maintenance in later life. However, very few studies have examined the brain MRI correlates of musical training in older adults. One previous cross-sectional study of 73 older adults with varying levels of musical training experience (defined as extent of musical training and practice and level of self-assessed musicianship) found that musical training was positively correlated with volume of the inferior frontal gyrus and parahippocampus (Chaddock-Heyman et al., 2021). The authors did not control the analysis for age, sex or years of education; however, these variables were not significantly correlated with musical training in this sample. Findings from two other cross-sectional studies with younger and older adult participants indicate that musical training could be associated with greater resilience to age-related brain changes. Sluming et al. (2002) found a significant negative correlation between hemisphere volumes and age (range 26-66 years) in 26 non-musicians but no correlation between these variables in 26 professional musicians (matched for sex, cognitive ability and handedness). Similar results were reported in another cross-sectional study with 125 participants (Rogenmoser et al., 2018) albeit with a younger age range (17-39 years); musicians (amateur and professional) had younger appearing brains (as indexed by a “BrainAge” score) than non-musicians. These participant groups were matched for age, sex, education and engagement in other leisure activities. While these studies indicate that musical training could be associated with markers of brain reserve or maintenance in older age, this evidence base is still limited as few studies have examined the MRI correlated of musical training in older adults specifically (with the exception of Chaddock-Heyman et al., 2021). Consequently, it is unknown whether musical training is associated with global brain macro- or micro-structural properties, differences in specific cortical and subcortical regions, or the integrity of specific white matter tracts in older age. Furthermore, there have been no longitudinal studies examining the potential association between musical training and changes in brain MRI measures with ageing. This limitation is important as only longitudinal analysis can differentiate between processes related to brain reserve and brain maintenance (Tucker-Drob & Salthouse, 2011). The present study will address each of the limitations outlined above using longitudinal data from the Lothian Birth Cohort 1936 (LBC1936). Participants have already completed four MRI assessments, between ages 73 and 82 (Taylor et al., 2018), and recently reported their lifetime experience of playing a musical instrument, at age 82 (Okely et al., 2021). In this participant sample, 40% reported some experience of playing a musical instrument; most of these participants reached a beginner or intermediate level of performance and practiced mostly in childhood. Experience of playing a musical instrument (indexed by number of musical instruments played, years of formal training, years of regular practice, hours of practice per week, and ability level) will be treated as a continuous variable with those with the most experience at one end of the continuum and participants with no experience of playing a musical instrument at the other. We will firstly test whether experience of playing a musical instrument is associated with global MRI measures including total brain volume, grey and normal-appearing white matter volumes, white matter hyperintensity volume, and white matter microstructure (from diffusion MRI) at age 73 or less decline in these brain MRI measures between ages 73 and 82. Secondly we will test whether musical experience playing a musical instrument is associated with level or change in the volume of specific cortical and sub cortical regions or the integrity of specific white matter tracts. Because very few studies have examined the MRI correlates of musical training in older adults or among individuals with former or lower levels of musical training (i.e. beginner or intermediated levels of performance) we will not limit this analysis to specific regions or white matter tracts based on previous findings; rather, we will apply an exploratory approach testing for associations with all available cortical and subcortical regions and white matter tracts in the LBC1936 dataset. We will test for associations between experience playing a musical instrument and 1) the volume of 34 cortical and 7 subcortical regions of interest at age 73; 2) declines in these regional volumes between ages 73 and 82; 3) the microstructure of 12 white matter tracts at age 73; and 4) microstructural changes in these tracts between ages 73 and 82. These analyses will be controlled for potentially confounding variables including childhood cognitive ability, years of education, socio-economic status, health behaviours and disease history. |
