Functional Connectivity in the Default Mode Network is Reduced in Association with Nocturnal Awakening in Mild Cognitive Impairment

Article type: Research Article

Authors: McKinnon, Andrew C.^{a; d} | Duffy, Shantel L.^{a; c} | Cross, Nathan E.^{a; e} | Terpening, Zoe^a | Grunstein, Ron R.^e | Lagopoulos, Jim^a | Batchelor, Jennifer^d | Hickie, Ian B.^a | Lewis, Simon J.G.^a | Shine, James M.^a | Naismith, Sharon L.^{a; b; c; *}

Affiliations: [a] Healthy Brain Ageing Program, The University of Sydney, Camperdown NSW, Australia | [b] School of Psychology, The University of Sydney, Camperdown NSW, Australia | [c] Charles Perkins Centre and Brain and Mind Centre, The University of Sydney, Camperdown NSW, Australia | [d] Department of Psychology, Macquarie University, Sydney NSW, Australia | [e] Woolcock Institute of Medical Research, Glebe NSW, Australia

Correspondence: [*] Correspondence to: Prof. Sharon Naismith, Head, Healthy Brain Ageing Program, 100 Mallett Street, Camperdown NSW 2050, Australia. Tel.: +612 9351 0781; Fax: +612 9351 0855; E-mail: sharon.naismith@sydney.edu.au.

Abstract: Background: Sleep disturbance is prevalent in MCI, and is a risk factor for cognitive deterioration. Objective: To identify functional connectivity deficits in the default mode network (DMN) in patients with mild cognitive impairment (MCI) and sleep disturbance, relative to MCIs with intact sleep. Methods: Participants comprised 47 adults aged 55 years and over, recruited from the Healthy Brain Ageing Clinic at the Brain and Mind Centre, Sydney, Australia. This sample contained 15 controls and 32 participants meeting criteria for MCI. Participants underwent resting-state fMRI and actigraphy, along with comprehensive neuropsychological, medical and psychiatric assessment. MCIs were split into two groups according to average wake after sleep onset (WASO) per night. WASO equal to or greater than 1 standard deviation (SD) above the control mean was deemed to reflect disturbed sleep. There were 11 patients in the MCI sleep-disturbed group, and 21 in the MCI sleep-intact group. Results: Relative to controls, MCIs demonstrated significant connectivity reductions between parietal and temporoparietal regions, and between temporal regions. Relative to MCIs with intact sleep, MCIs with sleep disturbance demonstrated reductions in functional connectivity between temporal and parietal regions, and between temporal and temporoparietal regions. Conclusions: MCIs with nocturnal awakenings demonstrate reductions in DMN connectivity. These reductions comprise brain regions that are crucially involved in sleep and memory processes. These results strengthen our previous findings, which found reduced connectivity in MCIs with self-reported sleep disturbances. Future studies may build on these findings through incorporating complementary neuroimaging techniques and experimental manipulations of sleep.

Keywords: Actigraphy, default mode network, memory, mild cognitive impairment, sleep

DOI: 10.3233/JAD-160922

Journal: Journal of Alzheimer's Disease, vol. 56, no. 4, pp. 1373-1384, 2017