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Frontal–temporal regional differences in brain energy metabolism and mitochondrial function using 31P MRS in older adults

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Abstract

Aging is a major risk for cognitive decline and transition to dementia. One well-known age-related change involves decreased brain efficiency and energy production, mediated in part by changes in mitochondrial function. Damaged or dysfunctional mitochondria have been implicated in the pathogenesis of age-related neurodegenerative conditions like Alzheimer’s disease (AD). The aim of the current study was to investigate mitochondrial function over frontal and temporal regions in a sample of 70 cognitively normal older adults with subjective memory complaints and a first-degree family history of AD. We hypothesized cerebral mitochondrial function and energy metabolism would be greater in temporal as compared to frontal regions based on the high energy consumption in the temporal lobes (i.e., hippocampus). To test this hypothesis, we used phosphorous (31P) magnetic resonance spectroscopy (MRS) which is a non-invasive and powerful method for investigating in vivo mitochondrial function via high energy phosphates and phospholipid metabolism ratios. We used a single voxel method (left temporal and bilateral prefrontal) to achieve optimal sensitivity. Results of separate repeated measures analyses of variance showed 31P MRS ratios of static energy, energy reserve, energy consumption, energy demand, and phospholipid membrane metabolism were greater in the left temporal than bilateral prefrontal voxels. Our findings that all 31P MRS ratios were greater in temporal than bifrontal regions support our hypothesis. Future studies are needed to determine whether findings are related to cognition in older adults.

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Data Availability

Data are managed under the data sharing agreement established with NIA and the parent R01 clinical trial Data Safety and Monitoring Board (DSMB) in the context of a phase II clinical trial (REVITALIZE, R01AG064587). All trial data will be made publicly available 2 years after completion of the parent clinical trial, per NIA and DSMB agreement.

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Acknowledgements

We would like to thank all the research participants at the McKnight Brain Institutes of the Universities of Florida (UF) and Arizona (UA), who generously volunteered their time and effort to help make this manuscript possible. We want to also thank to all research team members at the UF-Cognitive Neuroscience Lab and UA-Brain Imaging, Behavior and Aging Lab for their contributions to this project.

Funding

This study was supported by the National Institutes of Health (R01AG64587, F31AG071264, T32NS082168), the University of Florida and Arizona Evelyn F. McKnight Brain Institute, and University of Florida Norman Fixel Institute for Neurological Diseases.

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Authors and Affiliations

  1. Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, PO Box 100165, Gainesville, FL, 32610, USA

    Francesca V. Lopez, Adam J. Woods & Dawn Bowers

  2. Center for Cognitive Aging and Memory, Evelyn F. McKnight Brain Institute, University of Florida, Gainesville, FL, USA

    Andrew O’Shea & Adam J. Woods

  3. Department of Biostatistics, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA

    Zhiguang Huo

  4. Department of Neurology, Fixel Center for Neurological Diseases, College of Medicine, and Evelyn F. McKnight Brain Institute, University of Florida, Gainesville, FL, USA

    Steven T. DeKosky

  5. Department of Biomedical Engineering, College of Engineering, and Evelyn F. McKnight Brain Institute, University of Arizona and Alzheimer’s Disease Consortium, Tucson, AZ, USA

    Theodore P. Trouard

  6. Department of Psychology and Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, AZ, USA

    Gene E. Alexander

  7. Department of Psychiatry, Neuroscience and Physiological Sciences Graduate Interdisciplinary Programs, and BIO5 Institute, University of Arizona and Arizona Alzheimer’s Disease Consortium, Tucson, AZ, USA

    Gene E. Alexander

  8. Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA

    Adam J. Woods

  9. Department of Neurology, Fixel Center of Neurological Diseases, College of Medicine, University of Florida, Gainesville, FL, USA

    Dawn Bowers

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  1. Francesca V. Lopez
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Correspondence to Francesca V. Lopez.

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Lopez, F.V., O’Shea, A., Huo, Z. et al. Frontal–temporal regional differences in brain energy metabolism and mitochondrial function using 31P MRS in older adults. GeroScience 46, 3185–3195 (2024). https://doi.org/10.1007/s11357-023-01046-3

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  • DOI: https://doi.org/10.1007/s11357-023-01046-3

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