Brain metabolites are associated with sleep architecture and cognitive functioning in older adults.

Sleep deficits are a possible risk factor for development of cognitive decline and dementia in older age. Research suggests that neuroinflammation may be a link between the two. This observational, cross-sectional study evaluated relationships between sleep architecture, neuroinflammation and cognitive functioning in healthy older adults. Twenty-two adults aged ≥60 years underwent whole-brain magnetic resonance spectroscopic imaging ( in vivo method of visualizing increased brain temperatures as a proxy for neuroinflammation), supervised laboratory-based polysomnography, and comprehensive neurocognitive testing. Multiple regressions were used to assess relationships between magnetic resonance spectroscopic imaging-derived brain temperature and metabolites related to inflammation (choline; myo -inositol; N -acetylaspartate), sleep efficiency, time and % N3 sleep and cognitive performance. Choline, myo -inositol and N -acetylaspartate were associated with sleep efficiency and cognitive performance. Higher choline and myo -inositol in the bilateral frontal lobes were associated with slower processing speed and lower sleep efficiency. Higher choline and myo -inositol in bilateral frontoparietal regions were associated with better cognitive performance. Higher N -acetylaspartate around the temporoparietal junction and adjacent white matter was associated with better visuospatial function. Brain temperature was not related to cognitive or sleep outcomes. Our findings are consistent with the limited literature regarding neuroinflammation and its relationships with sleep and cognition in older age, which has implicated ageing microglia and astrocytes in circadian dysregulation, impaired glymphatic clearance and increased blood-brain barrier integrity, with downstream effects of neurodegeneration and cognitive decline. Inflammatory processes remain difficult to measure in the clinical setting, but magnetic resonance spectroscopic imaging may serve as a marker of the relationship between neuroinflammation, sleep and cognitive decline in older adults.
Competing Interests: A.W.A. received grant funding from the NIH NICHD and serves as an investigator for studies sponsored by the Michael J Fox Foundation for Parkinson’s Research, Aligning Science Across Parkinson’s (ASAP) Initiative, NIH NINDS, Eli Lilly and Company, Bial R&D Investments, S.A. She is a consultant for PhotoPharmics, Inc., and Grey Matter Technologies, a subsidiary of Modality.ai. J.P.S. was funded by the National Institutes of Health, National Science Foundation, Department of Defense, the State of Alabama, Shor Foundation for Epilepsy Research, UCB Pharma Inc., NeuroPace Inc., Greenwich Biosciences Inc., Biogen Inc., Xenon Pharmaceuticals, Serina Therapeutics Inc. and Eisai, Inc. He participates in the following consulting activities/advisory Boards: Greenwich Biosciences Inc., Pure Tech Health Inc., NeuroPace, Inc., Serina Therapeutics Inc., AdCel Biopharma Inc., iFovea Inc., LivaNova Inc., UCB Pharma Inc., SK Lifesciences Inc. and medico-legal services. He receives remuneration for editorial work as Editor-in-Chief for Epilepsy and Behavior Reports. He served as a member on the Alabama State Medical Cannabis Study Commission (nominated by Gov. Kay Ivey). He also serves on the Alabama Medical Cannabis Commission (2021–25; nominated by Dr. Scott Harris, State Health Officer). The remaining authors declare no conflicts of interest with this study.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)