Jeremiah Peiffer

Background
Sarcopenia, an age-related loss of skeletal muscle strength, mass and function, is linked with dementia and Alzheimer's disease (AD). Current guideline-recommended tools to diagnose sarcopenia, such as appendicular skeletal muscle mass (ASM), calculated as the sum of lean muscle mass in the arms and legs via dual-energy X-ray absorptiometry (DXA), are not commonly done in AD studies. However, brain magnetic resonance imaging (MRI) is regularly performed in AD studies, and temporalis muscle thickness (TMT) has been suggested as a potential sarcopenia biomarker. As a first step in evaluating whether TMT could be a useful sarcopenia diagnostic tool, we aimed to ascertain if TMT correlates with ASM in healthy older adults.

Method
We conducted a retrospective study of healthy cognitively-unimpaired older adults in the Intense Physical Activity and Cognition study, in whom MRI and DXA had been performed on the same visit. TMT was measured on axial T1-weighted MRIs bilaterally perpendicular to the long-axis of the temporalis muscle using the orbital roof and Sylvian fissure as anatomical landmarks, and average TMT used for analysis. ASM was adjusted for body size (height2). Sarcopenia was defined as ASM< 7.0 kg/m2 for males and <5.5 kg/m2 for females as per the 2019 European working group on sarcopenia in older people criteria. Pearson correlation assessed the relationship between TMT and ASM or age.

Result
There were 95 participants (mean±standard deviation [SD] age 69.1±5.2 years, 53% female, median Montreal Cognitive Assessment score 27 [Interquartile range 25 – 28],11% had sarcopenia). The mean±SD ASM was 7.0±1.2 kg/m2 and TMT was 7.3±1.2 mm. TMT and ASM were moderately correlated (r = 0.41, 95% confidence interval 0.23 – 0.56). TMT did not correlate with age but differed significantly between those with (mean±SD 7.4±1.2) and without sarcopenia (mean±SD 6.2±0.8, p = 0.004).

Conclusion
Among a cohort of cognitively-unimpaired older adults, TMT demonstrated moderate correlation with ASM. While futher studies are needed, these findings suggest that MRI-based assessement of TMT could be a practical tool to diagnose sarcopenia in AD studies. Future studies in AD patients should explore the relationship between TMT and long-term clinical and functional outcomes.

Project Description: Identification of lifestyle and dietary modifications which prevent or delay cognitive decline and Alzheimer's disease (AD) onset would confer significant social and economic benefit. However, there is a relative lack of large-scale investigations of lifestyle-related factors impacting cognitive decline and AD-related pathology. There is a critical need for longitudinal data collected from well-characterised ageing cohorts, and assessment of lifestyle in the context of Apolipoprotein E (APOE) genotype to facilitate development of strategies tailored to the needs of APOE ε4 allele carriers for whom prognosis is currently poorest. We report on dietary and physical activity data collected from healthy control participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing. The Cancer Council of Victoria Food Frequency Questionnaire was used to evaluate dietary pattern adherence (n=527), and physical activity levels were determined by self-report using the International Physical Activity Questionnaire (n=124). These measures were subsequently analysed in conjunction with APOE genotype, Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, neuroimaging and comprehensive neuropsychological assessment data. Linear mixed model analyses revealed that higher baseline adherence to a 'healthy' Mediterranean diet pattern was associated with reduced decline in the executive function cognitive domain after 36 months amongst APOE Ɛ4 allele carriers (p<0.01). Conversely, higher adherence to an 'unhealthy' western diet pattern at baseline was associated with greater decline after 36 months in the visuospatial cognitive domain in APOE Ɛ4 allele non-carriers (p<0.01).Hierarchical regressions demonstrated an association between higher levels of physical activity and larger hippocampal volume as determined by Magnetic Resonance Imaging (β=0.19;p<0.05). When stratified by BDNF Val66Met polymorphism and APOE Ɛ4 allele, physical activity was associated with larger hippocampal and temporal lobe volumes in the Val/Val homozygote group for the BDNF Val66Met polymorphism, and the relationship between physical activity and temporal lobe volume amongst Val/Val homozygotes was dependent on APOE ε4 allele carriage (β=-0.38;p<0.05). We have previously reported that brain and blood Aβ levels are modulated by physical activity by APOE genotype-dependent mechanisms. Taken together, our results are suggestive of differential effects of lifestyle factors on aspects of cognitive decline and AD-related pathology that are contingent on APOE Ɛ4 allele carriage.