Association of Anterior Cingulate Glutathione with Sleep Apnea in Older Adults At-Risk for Dementia

Abstract

Study objectives: Sleep disordered breathing (SDB) is common in older adults and is strongly associated with cognitive decline, with increasing evidence suggesting that it may represent a risk factor for dementia. Given that SDB is characterized by intermittent episodes of hypoxemia during sleep, it is possible that cognitive impairment may relate to cerebral oxidative stress. This study aimed to examine the relationship between nocturnal markers of hypoxemia and proton magnetic resonance spectroscopy ((1)H-MRS) markers of oxidative stress within the anterior cingulate cortex (ACC) of the brain.

Methods: Twenty-four older adults (mean age = 67.9 y) at-risk for dementia were recruited from our Healthy Brain Ageing Research Clinic. At-risk was defined as participants seeking help for assessment and/or intervention for cognitive decline, including those with subjective and/or objective cognitive complaints. This could occur in the context of prior depression or risk factors (e.g., vascular) for dementia. All participants underwent psychiatric, medical and neuropsychological assessment followed by overnight polysomnography. In addition, participants underwent (1)H-MRS to derive levels of ACC metabolite glutathione (GSH) reported as a ratio to creatine (GSH/Cr).

Results: Increased levels of GSH/Cr were associated with lower oxygen desaturation (r = -0.54, P = 0.007) and more severe apnea-hypopnea index scores during rapid eye movement sleep (r = 0.42, P = 0.050). In addition, ACC GSH/Cr correlated with poorer executive functioning (i.e., response inhibition: r = -0.49, P = 0.015; set shifting: r = -0.43, P = 0.037).

Conclusions: Markers of nocturnal hypoxemia and SDB are associated with cerebral oxidative stress in older people at-risk for dementia, suggesting a potential mechanism by which SDB may contribute to brain degeneration, cognitive decline, and dementia. Further work focused on utilizing this biomarker for the early identification and treatment of this possible modifiable risk factor in older persons is now warranted.

Keywords: anterior cingulate cortex; executive function; glutathione; oxidative stress; oxygen desaturation; proton magnetic resonance spectroscopy; sleep apnea.

Figure 1

Diagram demonstrating the anterior cingulate cortex voxel placement and LCModel output for one participant. The GSH metabolite peak is resolved at 2.95 ppm and is labelled in the water suppressed spectra. GSH, glutathione.

Figure 2

Graphs demonstrating correlations between glutathione (GSH/Cr) and measures of hypoxemia and rapid eye movement sleep apnea-hypopnea index in patients at-risk for dementia. AHI, apnea-hypopnea index; REM, rapid eye movement.