Insomnia Symptoms and Biomarkers of Alzheimer’s Disease in the Community

Article type: Research Article

Authors: Nicolazzo, Jessica^a | Cavuoto, Marina^a | Rowsthorn, Ella^a | Cribb, Lachlan^a | Bransby, Lisa^a | Gibson, Madeline^a | Wall, Prudence^a | Velakoulis, Dennis^{b; c} | Eratne, Dhamidhu^{b; c} | Buckley, Rachel^{d; e; f} | Yassi, Nawaf^{g; h} | Yiallourou, Stephanie^a | Brodtmann, Amy^{i; j; k} | Hamilton, Garun S.^{l; m} | Naughton, Matthew T.ⁿ | Lim, Yen Ying^a | Pase, Matthew P.^{a; o; *}

Affiliations: [a] The Turner Institute for Brain and Mental Health, Monash University, Clayton, VIC, Australia | [b] Neuropsychiatry at The Royal Melbourne Hospital, Parkville, VIC, Australia | [c] Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia | [d] Melbourne School of Psychological Sciences, University of Melbourne, Parkville, VIC, Australia | [e] Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA | [f] Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA | [g] Department of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia | [h] Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia | [i] The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia | [j] Department of Neurology, Austin Health, Melbourne, VIC, Australia | [k] Eastern Cognitive Disorders Clinic, Eastern Health, Monash University, Clayton, VIC, Australia | [l] Monash Lung, Sleep, Allergy and Immunology, Monash Health, Clayton, VIC, Australia | [m] School of Clinical Sciences, Monash University, Clayton, VIC, Australia | [n] Department of Respiratory Medicine, Alfred Health and Monash University, Melbourne, VIC, Australia | [o] Harvard T.H. Chan School of Public Health, Boston, MA, USA

Correspondence: [*] Correspondence to: A/Prof Matthew Pase, PhD, 18 Innovation Walk, Monash University, Clayton, Australia, 3800. Tel.: +61 401 267 924; E-mail: matthewpase@gmail.com.

Abstract: Background:Insomnia is one of the most common sleep disorders yet its relationship to the biology of Alzheimer’s disease remains equivocal. Objective:We investigated the cross-sectional relationship between insomnia symptom severity and cerebrospinal fluid (CSF) concentrations of Alzheimer’s disease biomarkers in a cognitively unimpaired middle-aged community sample. Methods:A total of 63 participants from the Healthy Brain Project (age = 59±7 years; 67% women) completed a lumbar puncture and two weeks of actigraphy to measure two of insomnia’s core features: difficulty initiating sleep (prolonged sleep onset latency) and difficulty maintaining sleep (wake after sleep onset [WASO] and number of awakenings). Additionally, the Insomnia Severity Index (ISI) was completed by 58 participants. Linear and Tobit regression were used to estimate the associations between each insomnia variable and CSF Aβ42, phosphorylated tau 181 (p-tau181), total-tau, and neurofilament light chain protein (NfL), adjusting for age, sex, and APOE ɛ4 genotype. Results:Higher ISI score was associated with greater average levels of CSF Aβ42 (per point: 30.7 pg/mL, 95% CI: 4.17–57.3, p = 0.023), as was higher WASO (per 10 min: 136 pg/mL, 95% CI: 48–223, p = 0.002) and more awakenings (per 5:123 pg/mL, 95% CI = 55–192, p < 0.001). Difficulty initiating sleep was not associated with CSF Aβ42, nor were insomnia features associated with p-tau181, total-tau, or NfL levels. Conclusion:Insomnia symptoms were associated with higher CSF Aβ42 levels in this relatively young, cognitively unimpaired sample. These findings may reflect increased amyloid production due to acute sleep disruption.

Keywords: Alzheimer’s disease, amyloid, dementia, insomnia, sleep

DOI: 10.3233/JAD-220924

Journal: Journal of Alzheimer's Disease, vol. 91, no. 4, pp. 1423-1434, 2023