Association between Sleep Disturbances and Medial Temporal Lobe Volume in Older Adults with Mild Cognitive Impairment Free of Lifetime History of Depression

Article type: Research Article

Authors: Yuen, Kimberley^{a; 1} | Rashidi-Ranjbar, Neda^{d; e} | Verhoeff, Nicolaas Paul L.G.^{b; c} | Kumar, Sanjeev^{c; e} | Gallagher, Damien^{c; g} | Flint, Alastair J.^{c; h} | Herrmann, Nathan^{c; g} | Pollock, Bruce G.^{c; e} | Mulsant, Benoit H.^{c; e} | Rajji, Tarek K.^{c; e} | Voineskos, Aristotle N.^{c; e} | Fischer, Corinne E.^{c; f; 2} | Mah, Linda^{a; b; c; *} | for the PACt-MD Study Group

Affiliations: [a] Rotman Research Institute, Baycrest Health Sciences, North York, Ontario, Canada | [b] Baycrest Health Sciences Department of Psychiatry, North York, Ontario, Canada | [c] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada | [d] Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada | [e] Centre for Addiction and Mental Health, Toronto, Ontario, Canada | [f] Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada | [g] Sunnybrook Health Sciences, Toronto, Ontario, Canada | [h] University Health Network, Toronto, Ontario, Canada

Correspondence: [*] Correspondence to: Linda Mah, MD, MHSc, Rotman Research Institute, Baycrest Health Sciences, 3560 Bathurst Street, North York, Ontario, M6A 2E Canada. Tel.: +1 416 785 2500/Ext. 3365; Fax: +1 416 785 4230; E-mail: [email protected].

Note: [1] Present address: Queen’s University School of Medicine, Kingston, Ontario, Canada.

Note: [2] Co-senior author.

Abstract: Background:Previous studies examining the link between neuropsychiatric symptoms (NPS) and biomarkers of Alzheimer’s disease (AD) may be confounded by remitted or past history of psychiatric illness, which in itself is associated with AD biomarkers such as reduced medial temporal lobe (MTL) volume. Objective:We examined associations between mood and anxiety-related NPS and MTL in older adults with mild cognitive impairment (MCI) free of lifetime history of depression. We hypothesized an inverse relationship between NPS severity and MTL. Methods:Forty-two MCI participants without current or past history of depression or other major psychiatric illness were assessed using the Neuropsychiatric Inventory-Questionnaire (NPI-Q). Correlation and regression analyses were performed between selected NPI-Q items and regional MTL volumes from structural magnetic resonance imaging. Results:Sleep disturbances were inversely associated with several regional volumes within the MTL. Sleep disturbances remained significantly correlated with left hippocampal and amygdala volume following correction for multiple comparisons. In contrast, depression and anxiety were not correlated with MTL. Conclusions:The relationship between reduced MTL and sleep, but not with depressed or anxious states, in MCI free of lifetime history of depression, suggests a potential mechanism for sleep as a risk factor for AD. The current findings highlight the importance of accounting for remitted psychiatric conditions in studies of the link between NPS and AD biomarkers and support the need for further research on sleep as clinical biomarker of AD and target for AD prevention.

Keywords: Alzheimer’s disease, depression, medial temporal lobe, mild cognitive impairment, neuroimaging biomarkers, neuropsychiatric symptoms, sleep

DOI: 10.3233/JAD-190160

Journal: Journal of Alzheimer's Disease, vol. 69, no. 2, pp. 413-421, 2019