Dissociation of Arousal Index Between REM and NREM Sleep in Elderly Adults with Cognitive Impairment, No Dementia: A Pilot Study

Article type: Research Article

Authors: Rosales-Lagarde, Alejandra^{a; b} | Cubero-Rego, Lourdes^{c; *} | Menéndez-Conde, Federico^d | Rodríguez-Torres, Erika E.^d | Itzá-Ortiz, Benjamín^d | Martínez-Alcalá, Claudia^{a; e} | Vázquez-Tagle, Génesis^e | Vázquez-Mendoza, Enrique^d | Eraña Díaz, Marta L.^f

Affiliations: [a] CONACyT Chairs, National Council of Science and Technology, Mexico | [b] National Institute of Psychiatry Ramón de la Fuente Muñiz, Mexico | [c] Neurodevelopmental Research Unit, Institute of Neurobiology, National Autonomous University of Mexico, Campus Juriquilla-Queretaro, Querétaro, México | [d] Mathematics Research Center, Autonomous University of the State of Hidalgo, Mexico | [e] Institute of Health Sciences, Autonomous University of the State of Hidalgo, Mexico | [f] Center for Research in Engineering and Applied Sciences, Autonomous University of the State of Morelos, Mexico

Correspondence: [*] Correspondence to: Lourdes Cubero-Rego, MD, PhD, Neurodevelopmental Research Unit Institute of Neurobiology, UNAM, Campus Juriquilla-Queretaro, Boulevard Juriquilla 3001, Querétaro 76230, México. Tel.: +52 442 1926101; E-mail: [email protected].

Abstract: Background:Sleep disruption in elderly has been associated with an increased risk of cognitive impairment and its transition into Alzheimer’s disease (AD). High arousal indices (AIs) during sleep may serve as an early-stage biomarker of cognitive impairment non-dementia (CIND). Objective:Using full-night polysomnography (PSG), we investigated whether CIND is related to different AIs between NREM and REM sleep stages. Methods:Fourteen older adults voluntarily participated in this population-based study that included Mini-Mental State Examination, Neuropsi battery, Katz Index of Independence in Activities of Daily Living, and single-night PSG. Subjects were divided into two groups (n = 7 each) according to their results in Neuropsi memory and attention subtests: cognitively unimpaired (CU), with normal results; and CIND, with –2.5 standard deviations in memory and/or attention subtests. AIs per hour of sleep during N1, N2, N3, and REM stages were obtained and correlated with Neuropsi total score (NTS). Results:AI (REM)  was significantly higher in CU group than in CIND group. For the total sample, a positive correlation between AI (REM)  and NTS was found (r = 0.68, p = 0.006), which remained significant when controlling for the effect of age and education. In CIND group, the AI (N2)  was significantly higher than the AI (REM) . Conclusion:In CIND older adults, this attenuation of normal arousal mechanisms in REM sleep are dissociated from the relative excess of arousals observed in stage N2. We propose as probable etiology an early hypoactivity at the locus coeruleus noradrenergic system, associated to its early pathological damage, present in the AD continuum.

Keywords: Alzheimer’s disease, arousals, locus coeruleus, mild cognitive impairment, neuropsychological testing, polysomnography, REM sleep

DOI: 10.3233/JAD-230101

Journal: Journal of Alzheimer's Disease, vol. 95, no. 2, pp. 477-491, 2023