1 Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada.
2 Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
3 Research center of the Hôpital du Sacré-Coeur de Montréal, Montreal, QC, Canada.
4 Division of Neurology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
5 Institut Universitaire de Gériatrie de Montréal and CRIUGM, CIUSSS du Centre-Sud-de-l'Île-de-Montréal, Montreal, QC, Canada.
6 PERFORM Centre, Center for Studies in Behavioral Neurobiology, Department of Health, Kinesiology and Applied Physiology, Concordia University, Montreal, QC, Canada.
7 Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.

Study objectives: To identify the association between insomnia symptoms and signs of prodromal neurodegeneration, including an analysis of potential differences between sleep-onset and sleep-maintenance insomnia.

Methods: We included those aged 45-85 years, living in one of 10 Canadian provinces in between 2012-2015 (at the baseline), recruited via three population-based sampling methods. Insomnia symptoms were assessed using questions adapted/modified from the Pittsburgh Sleep Quality Index. A panel of potential prodromal neurodegenerative markers including self-reported symptoms and objective gait motor, cognitive, and autonomic variables were assessed cross-sectionally. We compared those who endorsed insomnia symptoms =3 times per week to controls, adjusting for age, sex and education via logistic regression.

Results: Overall, 2,051/30,097 people screened positive for sleep-onset insomnia alone and 4,333 for sleep-maintenance insomnia alone, while 2,371 endorsed both subtypes. On objective gait tests, participants with sleep-onset insomnia, but not sleep-maintenance insomnia, had worse balance (OR = 1.33[1.16,1.52]) and slower gait speed (OR = 1.52[1.34,1.73]). Although participants with any insomnia subtype endorsed more motor symptoms, these were more severe in those with sleep-onset insomnia (OR onset vs. maintenance = 1.13 [1.07,1.18]). On objective cognitive tests, those with sleep-maintenance insomnia scored normally. However, participants with sleep-onset insomnia performed worse on tests of verbal fluency (OR = 1.24[1.06,1.43]) immediate memory (OR = 1.23[1.08,1.41]), and prospective memory task (OR = 1.29[1.11,1.50]). The sleep-onset insomnia group also had lower heart rate variability (OR = 1.23[1.07,1.43]). Secondary analyses found generally similar results in young vs. older age of insomnia development.

Conclusions: Compared to maintenance insomnia, those with sleep-onset insomnia have more motor, cognitive and autonomic signs/symptoms. When evaluating neurodegenerative risk, differentiating insomnia subtypes may increase precision.