Neurocognitive correlates of cerebral mitochondrial function and energy metabolism using phosphorus magnetic resonance spectroscopy in older adults

Francesca V Lopez; Andrew O'Shea; Zhiguang Huo; Steven T DeKosky; Theodore P Trouard; Gene E Alexander; Adam J Woods; Dawn Bowers

doi:10.1007/s11357-024-01403-w

Neurocognitive correlates of cerebral mitochondrial function and energy metabolism using phosphorus magnetic resonance spectroscopy in older adults

Geroscience. 2024 Oct 31. doi: 10.1007/s11357-024-01403-w. Online ahead of print.

Authors

Francesca V Lopez¹, Andrew O'Shea², Zhiguang Huo³, Steven T DeKosky⁴, Theodore P Trouard⁵, Gene E Alexander^{6

7}, Adam J Woods^{8

2}, Dawn Bowers^{8

9}

Affiliations

¹ Department of Clinical and Health Psychology, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA. frl001@health.ucsd.edu.
² Center for Cognitive Aging and Memory, Evelyn F. McKnight Brain Institute, University of Florida, Gainesville, Gainesville, FL, USA.
³ Department of Biostatistics, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA.
⁴ Department of Neurology and Fixel Center for Neurological Diseases, College of Medicine, University of Florida and Evelyn F. McKnight Brain Institute, Gainesville, FL, USA.
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.
⁶ Department of Psychology and Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, AZ, USA.
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.
⁸ Department of Clinical and Health Psychology, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA.
⁹ Department of Neurology, Fixel Center of Neurological Diseases, College of Medicine, University of Florida, Gainesville, FL, USA.

PMID: 39477865
DOI: 10.1007/s11357-024-01403-w

Abstract

The goal of the current study was to learn about the role of cerebral mitochondrial function on cognition. Based on established cognitive neuroscience, clinical neuropsychology, and cognitive aging literature, we hypothesized mitochondrial function within a focal brain region would map onto cognitive behaviors linked to that brain region. To test this hypothesis, we used phosphorous (³¹P) magnetic resonance spectroscopy (MRS) to derive indirect markers of mitochondrial function and energy metabolism across two regions of the brain (bifrontal, left temporal). We administered cognitive tasks sensitive to frontal-executive or temporal-hippocampal systems to a sample of 70 cognitively unimpaired older adults with subjective memory complaints and a first-degree family history of Alzheimer's disease and predicted better executive function and recent memory performance would be related to greater frontal and temporal ³¹P MRS indirect markers, respectively. Results of separate hierarchical linear regressions indicated better recent memory scores were related to ³¹P MRS indirect markers of lower static energy and higher energy reserve within the left temporal voxel; these findings were associated with moderate effect sizes. Contrary to predictions, executive function performance was unrelated to ³¹P MRS indirect markers within the bilateral frontal voxel, which may reflect a combination of theoretical and/or methodological issues. Findings represent a snapshot of the relationship between cognition and ³¹P MRS indirect markers of mitochondrial function, providing potential avenues for future work investigating mitochondrial underpinnings of cognition. ³¹P MRS may provide a sensitive neuroimaging marker for differences in aspects of memory among persons at-risk for mild cognitive impairment or dementia.

Keywords: Executive function; Mitochondria; Older adults; Phosphate brain energy metabolism; Phosphorus magnetic resonance spectroscopy; Recent memory.

Abstract

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