Gait and balance disturbances are common in young urbanites and associated with cognitive impairment. Air pollution and the historical development of Alzheimer's disease in the young

Abstract

To determine whether gait and balance dysfunction are present in young urbanites exposed to fine particular matter PM 2.5 ≥ annual USEPA standard, we tested gait and balance with Tinetti and Berg tests in 575 clinically healthy subjects, age 21.0±5.7y who were residents in Metropolitan Mexico City, Villahermosa and Reynosa. The Montreal Cognitive Assessment was also applied to an independent cohort n:76, age 23.3± 9.1y. In the 575 cohort, 75.4% and 34.4% had abnormal total Tinetti and Berg scores and high risk of falls in 17.2% and 5.7% respectively. BMI impacted negatively Tinetti and Berg performance. Gait dysfunction worsen with age and males performed worse than females. Gait and balance dysfunction were associated with mild cognitive impairment MCI (19.73%) and dementia (55.26%) in 57/76 and 19 cognitively intact subjects had gait and balance dysfunction. Seventy-five percent of urbanites exposed to PM 2.5 had gait and balance dysfunction. For MMC residents-with historical documented Alzheimer disease (AD) and CSF abnormalities, these findings suggest Alzheimer Continuum is in progress. Early development of a Motoric Cognitive Risk Syndrome ought to be considered in city dwellers with normal cognition and gait dysfunction. The AD research frame in PM 2.5 exposed young urbanites should include gait and balance measurements. Multicity teens and young adult cohorts are warranted for quantitative gait and balance measurements and neuropsychological and brain imaging studies in high vs low PM 2.5 exposures. Early identification of gait and balance impairment in young air pollution-exposed urbanites would facilitate multidisciplinary prevention efforts for modifying the course of AD.

Quadruple abnormal protein aggregates in brainstem pathology and exogenous metal-rich magnetic nanoparticles (and engineered Ti-rich nanorods). The substantia nigrae is a very early target in young urbanites and the gastrointestinal tract a key brainstem portal

“…The brainstem and cerebellum are critical not only because they host key networks modulating autonomic function, arousal, motor control and emotions, [64][65][66][67]97 but because damage to specific nuclei and network connections shed light on associated early clinical manifestations and critical portals of entry of our culprit: metal-rich exogenous nanoparticles. 98 The dominant presence of Fe, Al and Ti in the NPs present in substantia nigrae (SN) mitochondria, points unequivocally to their exogenous sources -including engineered Ti-rich nanorods-, and raising serious concerns. TiO2 NPs are widely manufactured for use in both domestic (e.g.…”

Brainstem Quadruple Aberrant Hyperphosphorylated Tau, Beta-Amyloid, Alpha-Synuclein and TDP-43 Pathology, Stress and Sleep Behavior Disorders

“…We open the discussion by emphasizing that this study explores a group of young, educated, middle-class and mostly female Mexican subjects, with significant published documentation of AD, PD and TDP-43 pathology, using forensic autopsy cases and extensive published cognitive, olfaction, gait and equilibrium and brainstem auditory evoked potentials (BAEPs) studies in matching populations—a situation that makes this study very different from the average PTSD and sleep behavior disorder cases in the literature: the average case focuses on individuals who are male, significantly older, of low socioeconomic status, and possess extensive co-morbidities [ 6 , 7 , 8 , 9 , 10 , 12 , 13 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 42 , 43 , 44 , 45 , 46 , 47 ].…”

“…(b) Olfactory bulb AD and PD pathology, along with olfaction deficits, are reported in MMC children and young adults and remarkably, Apolipoprotein E allele 4 carriers (APOE4) are 4.57 times more likely to die by suicide versus APOE 3 carriers, and have higher chances of exhibiting olfactory bulb neuronal alpha-synuclein aggregates and hyperphosphorylated tau neurites and tangles [ 8 , 47 ]. (c) Significant cognition deficits, gait, equilibrium and BAEPs abnormalities are present in seemingly MMC healthy children and young adults [ 13 , 45 , 46 ].…”

“… Distribution of misfolded proteins and neuropathological hallmarks in the brainstem and frontal cortex in Metropolitan Mexico City (MMC) individuals younger than 40 years [ 6 , 7 , 8 , 9 , 10 , 45 , 46 ]. The brainstem is an early target (motor, depression, arousal dysfunction and Autonomic Nervous System (ANS) dysfunction) [ 56 , 57 , 58 , 59 , 60 , 61 ] of misfolded proteins in Alzheimer, Parkinson and transactive response DNA-binding protein TDP-43 pathology in children and young adult residents in MMC [ 6 ].…”

The Relationship Between Four Measures of Religiosity and Cross-National Variations in the Burden of Dementia

“…A significant proportion of the risk for dementia, and particularly for AD, is determined by genetic factors [ 2 ]. However, the development and subsequent progression of dementia is influenced by several environmental factors, some of which, such as diet, exposure to environmental pollutants, and comorbid conditions such as depression or diabetes mellitus, are amenable to modification [ 3 , 4 ]. Likewise, certain factors have been identified as potentially protective against the development of dementia, including specific dietary patterns, levels of specific nutrients such as folate, and involvement in physical or cognitive activity [ 5 , 6 ].…”