Fall Risk, Sleep Behavior, and Sleep-Related Movement Disorders in Young Urbanites Exposed to Air Pollution

Article type: Research Article

Authors: Calderón-Garcidueñas, Lilian^{a; b; *} | Kulesza, Randy^c | Greenough, Glen P.^d | García-Rojas, Edgar^b | Revueltas-Ficachi, Paula^b | Rico-Villanueva, Adriana^b | Flores-Vázquez, Jorge Orlando^b | Brito-Aguilar, Rafael^b | Ramírez-Sánchez, Silvia^b | Vacaseydel-Aceves, Nora^e | Cortes-Flores, Ana Paulina^b | Mansour, Yusra^f | Torres-Jardón, Ricardo^g | Villarreal-Ríos, Rodolfo^h | Koseoglu, Emelⁱ | Stommel, Elijah W.^d | Mukherjee, Partha S.^j

Affiliations: [a] The University of Montana, Missoula, MT, USA | [b] Universidad del Valle de México, Mexico City, México | [c] Auditory Research Center, Lake Erie College of Osteopathic Medicine, Erie, PA, USA | [d] Department of Neurology, Geisel School of Medicine at Dartmouth, Hanover NH, USA | [e] Emergency Department, Hospital San Angel Inn Sur, Mexico City, Mexico | [f] Department of Otolaryngology –Head and Neck Surgery, Henry Ford Macomb Hospital, Clinton Township, MI, USA | [g] Instituto de Ciencias de la Atmósfera y Cambio Climático, Universidad Nacional, Autónoma de México, México | [h] Universidad Autónoma de Piedras Negras, Piedras Negras, Coahuila, México | [i] Neurology Department, Erciyes University, Kayseri, Turkey | [j] Interdisciplinary Statistical Research Unit, Indian Statistical Institute, Kolkata, India

Correspondence: [*] Correspondence to: Professor Lilian Calderón-Garcidueñas, MA, MD, PhD, University of Montana, 32 Campus Drive, 287 Skaggs Building, Missoula, MT 59812, USA. Tel.: +1 406 243 4785; E-mail: [email protected].

Abstract: Background:Quadruple aberrant hyperphosphorylated tau, amyloid-β, α-synuclein, and TDP-43 pathology had been documented in 202/203 forensic autopsies in Metropolitan Mexico City ≤40-year-olds with high exposures to ultrafine particulate matter and engineered nanoparticles. Cognition deficits, gait, equilibrium abnormalities, and MRI frontal, temporal, caudate, and cerebellar atrophy are documented in young adults. Objective:This study aimed to identify an association between falls, probable Rapid Eye Movement Sleep Behavior Disorder (pRBD), restless leg syndrome (RLS), and insomnia in 2,466 Mexican, college-educated volunteers (32.5±12.4 years). Methods:The anonymous, online study applied the pRBD and RLS Single-Questions and self-reported night-time sleep duration, excessive daytime sleepiness, insomnia, and falls. Results:Fall risk was strongly associated with pRBD and RLS. Subjects who fell at least once in the last year have an OR = 1.8137 [1.5352, 2.1426] of answering yes to pRBD and/or RLS questions, documented in 29% and 24% of volunteers, respectively. Subjects fell mostly outdoors (12:01 pm to 6:00 pm), 43% complained of early wake up hours, and 35% complained of sleep onset insomnia (EOI). EOI individuals have an OR of 2.5971 [2.1408, 3.1506] of answering yes to the RLS question. Conclusion:There is a robust association between falls, pRBD, and RLS, strongly suggesting misfolded proteinopathies involving critical brainstem arousal and motor hubs might play a crucial role. Nanoparticles are likely a significant risk for falls, sleep disorders, insomnia, and neurodegenerative lethal diseases, thus characterizing air particulate pollutants’ chemical composition, emission sources, and cumulative exposure concentrations are strongly recommended.

Keywords: Air pollution, Alzheimer’s disease, falls, Mexico City young urbanites, nanoparticles, PM_2.5 , possible REM sleep behavior disorder, quadruple proteinopathies, restless leg syndrome, TDP-43 proteinopathies

DOI: 10.3233/JAD-220850

Journal: Journal of Alzheimer's Disease, vol. 91, no. 2, pp. 847-862, 2023