Sleep matters: Neurodegeneration spectrum heterogeneity, combustion and friction ultrafine particles, industrial nanoparticle pollution, and sleep disorders—Denial is not an option

Sustained exposures to ubiquitous outdoor/indoor fine particulate matter (PM2.5), including combustion and friction ultrafine PM (UFPM) and industrial nanoparticles (NPs) starting in utero, are linked to early pediatric and young adulthood aberrant neural protein accumulation, including hyperphosphorylated tau (p-tau), beta-amyloid (Aβ1 − 42), α-synuclein (α syn) and TAR DNA-binding protein 43 (TDP-43), hallmarks of Alzheimer's (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). UFPM from anthropogenic and natural sources and NPs enter the brain through the nasal/olfactory pathway, lung, gastrointestinal (GI) tract, skin, and placental barriers. On a global scale, the most important sources of outdoor UFPM are motor traffic emissions. This study focuses on the neuropathology heterogeneity and overlap of AD, PD, FTLD, and ALS in older adults, their similarities with the neuropathology of young, highly exposed urbanites, and their strong link with sleep disorders. Critical information includes how this UFPM and NPs cross all biological barriers, interact with brain soluble proteins and key organelles, and result in the oxidative, endoplasmic reticulum, and mitochondrial stress, neuroinflammation, DNA damage, protein aggregation and misfolding, and faulty complex protein quality control. The brain toxicity of UFPM and NPs makes them powerful candidates for early development and progression of fatal common neurodegenerative diseases, all having sleep disturbances. A detailed residential history, proximity to high-traffic roads, occupational histories, exposures to high-emission sources (i.e., factories, burning pits, forest fires, and airports), indoor PM sources (tobacco, wood burning in winter, cooking fumes, and microplastics in house dust), and consumption of industrial NPs, along with neurocognitive and neuropsychiatric histories, are critical. Environmental pollution is a ubiquitous, early, and cumulative risk factor for neurodegeneration and sleep disorders. Prevention of deadly neurological diseases associated with air pollution should be a public health priority

Ethical Considerations in REM Sleep Behavior Disorder Ethical Perspectives

ABSTRACT A patient diagnosed with REM behavior sleep disorder (RBD) has as much as a 65% risk of developing an !-synucleinopathy. Currently, it is not possible to predict whether an individual will develop a disease, or, if so, which disease.The neurologist treating the patient must consider (1) the difference between disclosing a diagnosis and disclosing the risk of a diagnosis; (2) whether to disclose this risk to patients; and (3) if deciding to disclose the risk, the appropriate timing of such a conversation. Case Note: This is a hypothetical case. A 70-year-old man presented to the clinic at the insistence of his wife, who noted the gradual development of strange behaviors at night, including shouting, swearing, kicking, and punching. Her husband had been a sleeptalker and restless sleeper for many years. More recently, the episodes had become more violent, and his wife had bruises on her left arm and leg as a result of his nocturnal movements. She now slept in a different room. The patient was somewhat embarrassed. He was aware of nightmares and reported dreaming of muggers attacking him and his wife. In the dream, he would fight the assailants. Much to his chagrin, when he would awaken he would find he had been punching his wife. He had also injured himself, recently falling out of bed and sustaining a laceration over his eyebrow. Polysomnography revealed frequent periodic limb movements in non-REM sleep and elevated motor tone in REM sleep, which in conjunction with the history were consistent with the diagnosis of REM sleep behavior disorder (RBD). Because RBD is associated with an increased risk of developing a neurodegenerative disease, the neurologist felt that the risk should be disclosed to the patient and his wife, but a colleague advised that this would be unwarranted as it would only cause worry for them. This case raises the following ethical questions: 1. Should the physician disclose the risk of neurodegenerative disease in patients with RBD? If so, how? If not, why? 2. Does the disclosure of a diagnosis differ from the disclosure of a risk

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

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