Nocturnal Hypoxemia Is Associated with Altered Parahippocampal Functional Brain Connectivity in Older Adults at Risk for Dementia

Article type: Research Article

Authors: Naismith, Sharon L.^{a; b; c; f; *} | Duffy, Shantel L.^{a; b; c; f} | Cross, Nathan^{a; c; d} | Grunstein, Ron^{d; f} | Terpening, Zoe^{a; g} | Hoyos, Camilla^{a; c; d; f} | D’Rozario, Angela^{a; c; d; f} | Lagopoulos, Jim^e | Osorio, Ricardo S.^{h; i} | Shine, James M.^c | McKinnon, Andrew C.^{a; c; f}

Affiliations: [a] Healthy Brain Ageing Program, School of Psychology, University of Sydney, Sydney, Australia | [b] Charles Perkins Centre, University of Sydney, Sydney, Australia | [c] Brain & Mind Centre, University of Sydney, Sydney, Australia | [d] Sleep and Circadian Group, Woolcock Institute of Medical Research, Sydney Health Partners, Sydney, Australia | [e] Sunshine Coast Mind and Neuroscience Thompson Institute University of Sunshine Coast, Queensland, Australia | [f] NHMRC Centre of Research Excellence to Optimise Sleep in Brain Ageing and Neurodegeneration (CogSleep), Australia | [g] Faculty of Medicine, University of New South Wales, Sydney, Australia | [h] Department of Psychiatry, Sleep Aging and Memory Lab, NYU School of Medicine, New York, NY, USA | [i] Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA

Correspondence: [*] Correspondence to: Professor Sharon Naismith, Healthy Brain Ageing Program, University of Sydney, 100 Mallett St, Camperdown NSW 2050, Australia. Tel.: +612 9351 0781; Fax: +612 9351 0551; E-mail: [email protected].

Abstract: Background:Obstructive sleep apnea is associated with an increased risk of developing mild cognitive impairment and dementia. Intermittent nocturnal hypoxemia in obstructive sleep apnea is associated with brain changes in key regions that underpin memory. Objective:To determine whether older adults with severe nocturnal hypoxemia would exhibit reduced functional connectivity within these regions, with associated deficits in memory. Methods:Seventy-two participants 51 years and over underwent polysomnography with continuous blood oxygen saturation recorded via oximetry. The oxygen desaturation index (ODI, 3% dips in oxygen levels per hour) was the primary outcome measure. ODI was split into tertiles, with analyses comparing the lowest and highest tertiles (N = 48). Thirty-five of the 48 participants from these two tertiles had mild cognitive impairment. Participants also underwent resting-state fMRI and comprehensive neuropsychological, medical, and psychiatric assessment. Results:The highest ODI tertile group demonstrated significantly reduced connectivity between the left and right parahippocampal cortex, relative to the lowest ODI tertile group (t(42) = –3.26, p = 0.041, beta = –1.99).The highest ODI tertile group also had poorer working memory performance. In the highest ODI tertile group only, higher left-right parahippocampal functional connectivity was associated with poorer visual memory recall (between-groups z = –2.93, p = 0.0034). Conclusions:Older adults with severe nocturnal hypoxemia demonstrate impaired functional connectivity in medial temporal structures, key regions involved in sleep memory processing and implicated in dementia pathophysiology. Oxygen desaturation and functional connectivity in these individuals each relate to cognitive performance. Research is now required to further elucidate these findings.

Keywords: Alzheimer’s disease, default mode network, memory, mild cognitive impairment, obstructive sleep apnea

DOI: 10.3233/JAD-190747

Journal: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 571-584, 2020