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

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 preventable neurodegenerative lethal diseases, thus characterizing air particulate pollutants’ chemical composition, emission sources, and cumulative exposure concentrations are strongly recommended.

APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM2.5 Polluted Cities

“…Critical to this Review is the Arnsten et al [ 86 ] hypothesis that tau pathology within select projection neurons with susceptible microenvironments can initiate sporadic AD (sAD) and the equally remarkable observation by Braak and Del Tredeci [ 85 ] supporting the idea that axons of cortico-cortical top-down neurons in neocortical fields involved in AD are key for carrying and spreading abnormal tau trans synaptically into the distal dendritic segments of nerve cells following directly into the neuronal chain. The important documentation of tau seeding frequently preceding NFT pathology, e.g., in the substantia nigra pars compacta, and Bergmann glia, and the involvement of the intermediate reticular zone, dorsal raphe nucleus, and olfactory bulb [ 87 ] are of great relevance to our findings in Metropolitan Mexico City children and young adults [ 26 , 27 , 39 , 42 , 89 , 90 ].…”

“…Remarkably, FeNPs 4 ± 1 nm and Hg NPs 8 ± 2 nm were seen predominantly in the LC and substantia nigra (SN) [ 27 , 89 ]. NP damage to the substantia nigrae and cerebellum is outstanding and translates to autonomic dysfunction, gait and balance alterations, and cerebellar MRI atrophy in young MMC residents [ 41 , 89 , 90 , 101 , 198 ].…”

“…MMC young residents also have a significant risk of falling due to alterations in gait and equilibrium [ 90 , 198 ]. Central and peripheral auditory system dysfunction with abnormal brainstem auditory-evoked potentials starting in children 8.52 ± 3.3 y, young adults (21.08 ± 3.0 y), and middle-aged subjects 42.48 ± 8.5 y is likely related to the presence of P-tau, Aβ 42 , and α-synuclein within auditory and vestibular nuclei, along with the marked dysmorphology in the ventral cochlear nucleus and superior olivary complex [ 204 , 205 , 206 ].…”

“…Remarkably, FeNPs 4 ± 1 nm and Hg NPs 8 ± 2 nm were seen predominantly in the LC and substantia nigra (SN) [27,89]. NP damage to the substantia nigrae and cerebellum is outstanding and translates to autonomic dysfunction, gait and balance alterations, and cerebellar MRI atrophy in young MMC residents [41,89,90,101,198]. All children in the first decade of life had P-tau pre-tangle stages, and by the second decade, we documented neurofibrillary (NFT) tangles I-V [26,191].…”