To the Editor:
Gosselin and colleagues conducted a systematic review of the association between obstructive sleep apnea (OSA) and cognitive decline in older adults with special reference to aging, neurodegenerative mechanism in the brain, treatment effect, and future perspective (1). Although the content of this summary report is valid, I would like to add serum insulin and insulin activity in the brain, which seems indispensable for understanding the biological mechanism of cognitive decline in older adults.
Kullmann and colleagues investigated the effect of three doses of insulin as nasal sprays on the central and autonomous nervous systems (2). Although high-dose nasal insulin showed spillover into the bloodstream, nasal insulin dose-dependently modulated regional brain activity and normalized the high-frequency component of heart rate variability. Insulin activity in the brain is inversely related to serum insulin levels (3), and metabolic disorders caused by insulin resistance with hyperinsulinemia would be indirectly related to OSA and cognitive decline.
Rodríguez-Flores and colleagues investigated the association between obesity and the breath-holding index, which was measured by transcranial Doppler as an indicator of vasomotor reactivity of the brain (4). Subjects without diabetes mellitus and hypertension were selected, and there was a linear negative association between obesity and the breath-holding index, which was adjusted by insulin resistance. The authors concluded that insulin resistance made no contribution to the association between obesity and vasomotor reactivity of the brain, although obesity was closely associated with insulin resistance. There is a significant relationship between OSA and vasomotor reactivity of the brain, and the interrelationship among OSA, cognitive impairment, and depression should be comprehensively evaluated (5).
Lal and colleagues explored biomarkers of cognitive impairment in female patients with OSA who were 45–60 years of age (6). Pathway analysis showed that serum insulin was a prominent protein for regulating other significant biomarkers. In addition, advanced stages of cognitive impairment, such as Alzheimer’s disease, presented similar findings. Taken together, serum insulin and insulin in the brain might be one of the predictors of cognitive decline.
Supplementary Material
Footnotes
Originally Published in Press as DOI: 10.1164/rccm.201811-2173LE on January 16, 2019
Author disclosures are available with the text of this letter at www.atsjournals.org.
References
- 1.Gosselin N, Baril AA, Osorio RS, Kaminska M, Carrier J. Obstructive sleep apnea and the risk of cognitive decline in older adults. Am J Respir Crit Care Med. 2019;199:142–148. doi: 10.1164/rccm.201801-0204PP. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Kullmann S, Veit R, Peter A, Pohmann R, Scheffler K, Häring HU, et al. Dose-dependent effects of intranasal insulin on resting-state brain activity. J Clin Endocrinol Metab. 2018;103:253–262. doi: 10.1210/jc.2017-01976. [DOI] [PubMed] [Google Scholar]
- 3.Craft S. Insulin resistance and Alzheimer’s disease pathogenesis: potential mechanisms and implications for treatment. Curr Alzheimer Res. 2007;4:147–152. doi: 10.2174/156720507780362137. [DOI] [PubMed] [Google Scholar]
- 4.Rodríguez-Flores M, García-García E, Cano-Nigenda CV, Cantú-Brito C. Relationship of obesity and insulin resistance with the cerebrovascular reactivity: a case control study. Cardiovasc Diabetol. 2014;13:2. doi: 10.1186/1475-2840-13-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Kerner NA, Roose SP. Obstructive sleep apnea is linked to depression and cognitive impairment: evidence and potential mechanisms. Am J Geriatr Psychiatry. 2016;24:496–508. doi: 10.1016/j.jagp.2016.01.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Lal C, Hardiman G, Kumbhare S, Strange C. Proteomic biomarkers of cognitive impairment in obstructive sleep apnea syndrome. Sleep Breath. doi: 10.1007/s11325-018-1693-8. [online ahead of print] 2 Jul 2018; DOI: 10.1007/s11325-018-1693-8. [DOI] [PubMed] [Google Scholar]
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