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

Abstract 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 aging 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.