Increased Gain in the Auditory Pathway, Alzheimer’s Disease Continuum, and Air Pollution: Peripheral and Central Auditory System Dysfunction Evolves Across Pediatric and Adult Urbanites

2019 ◽  
Vol 70 (4) ◽  
pp. 1275-1286 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Randy J. Kulesza ◽  
Yusra Mansour ◽  
Mario Aiello-Mora ◽  
Partha S. Mukherjee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Auditory System ◽  
Auditory Pathway ◽  
Central Auditory System

Increased Gain in the Auditory Pathway, Alzheimer’s Disease Continuum, and Air Pollution: Peripheral and Central Auditory System Dysfunction Evolves Across Pediatric and Adult Urbanites

2021 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Randy J. Kulesza ◽  
Yusra Mansour ◽  
Mario Aiello-Mora ◽  
Partha S. Mukherjee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Young Adults ◽  
Evoked Potentials ◽  
Auditory Evoked Potentials ◽  
Auditory Pathway ◽  
Conduction Time ◽  
Brainstem Auditory Evoked Potentials ◽  
Noninvasive Biomarkers

A major impediment in early diagnosis of Alzheimer’s disease (AD) is the lack of robust non-invasive biomarkers of early brain dysfunction. Metropolitan Mexico City (MMC) children and young adults show hyperphosphorylated tau, amyloid-β, and α-synuclein within auditory and vestibular nuclei and marked dysmorphology in the ventral cochlear nucleus and superior olivary complex. Based on early involvement of auditory brainstem centers, we believe brainstem auditory evoked potentials can provide early AD biomarkers in MMC young residents. We measured brainstem auditory evoked potentials in MMC clinically healthy children (8.52 ± 3.3 years) and adults (21.08 ± 3.0 years, 42.48 ± 8.5 years, and 71.2 ± 6.4 years) compared to clean air controls (6.5 ± 0.7 years) and used multivariate analysis adjusting for age, gender, and residency. MMC children had decreased latency to wave I, delays in waves III and V, and longer latencies for interwave intervals, consistent with delayed central conduction time of brainstem neural transmission. In sharp contrast, young adults have significantly shortened interwave intervals I–III and I–V. By the 5th decade, wave V and interval I–V were significantly shorter, while the elderly cohort had significant delay in mean latencies and interwave intervals. Compensatory plasticity, increased auditory gain, cochlear synaptopathy, neuroinflammation, and AD continuum likely play a role in the evolving distinct auditory pathology in megacity urbanites. Understanding auditory central and peripheral dysfunction in the AD continuum evolving and progressing in pediatric and young adult populations may shed light on the complex mechanisms of AD development and help identify strong noninvasive biomarkers. AD evolving from childhood in air pollution environments ought to be preventable.

Auditory Brainstem Dysfunction, Non-Invasive Biomarkers for Early Diagnosis and Monitoring of Alzheimer’s Disease in Young Urban Residents Exposed to Air Pollution

2021 ◽  
Author(s):  
Yusra Mansour ◽  
Kaitlyn Blackburn ◽  
Luis Oscar González-González ◽  
Lilian Calderón-Garcidueñas ◽  
Randy J. Kulesza
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Early Diagnosis ◽  
Auditory Evoked Potentials ◽  
Strong Association ◽  
Amyloid Β ◽  
Auditory Pathway ◽  
Auditory Brainstem ◽  
Complex Sounds

Alzheimer’s disease (AD) is a biological construct defined by abnormal deposits of hyperphosphorylated tau and amyloid-β. The 2050 projection for AD in the USA is 14 million. There is a strong association between AD, air pollution, and traffic. Early diagnosis is imperative for intervention in the initial disease stages. Hearing and, specifically, the ability to encode complex sounds are impaired in AD. Nuclei in the auditory brainstem appear to be sensitive to neurodevelopmental and neurodegenerative disorders. Specifically, sustained exposure to air pollution is harmful to the brainstem; young residents of Metropolitan Mexico City (MMC) exposed to fine particulate matter and combustion-derived nanoparticles develop AD pathology in infancy. MMC clinically healthy children and teens have significant central delays in brainstem auditory evoked potentials (BAEPs). Herein, we review evidence that the auditory pathway is a key site of AD early pathology associated with air pollution and is significantly involved in AD patients. We strongly suggest electrophysiological screening, including BAEPs, be employed to screen individuals for early delays and to monitor progressive decline in patients diagnosed with mild cognitive impairment and AD. Understanding auditory dysfunction in early AD in pediatric and young adult populations may clarify mechanisms of disease progression. Air pollution is a risk factor for the development of AD and as the number of Americans with AD continues to grow without a cure, we need to focus on preventable, early causes of this fatal disease and intervene appropriately.

Non-Phosphorylated Tau in Cerebrospinal Fluid is a Marker of Alzheimer’s Disease Continuum in Young Urbanites Exposed to Air Pollution

2018 ◽  
Vol 66 (4) ◽  
pp. 1437-1451 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Partha S. Mukherjee ◽  
Katharina Waniek ◽  
Max Holzer ◽  
Chih-kai Chao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Cerebrospinal Fluid ◽  
Phosphorylated Tau

scholarly journals Are noise and air pollution related to the incidence of dementia? A cohort study in London, England

BMJ Open ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. e022404 ◽  
Author(s):  
Iain M Carey ◽  
H Ross Anderson ◽  
Richard W Atkinson ◽  
Sean D Beevers ◽  
Derek G Cook ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Cohort Study ◽  
Vascular Dementia ◽  
Care Home ◽  
Secondary Outcome ◽  
Area Deprivation ◽  
Diagnosis Of Dementia ◽  
Incidence Of Dementia

ObjectiveTo investigate whether the incidence of dementia is related to residential levels of air and noise pollution in London.DesignRetrospective cohort study using primary care data.Setting75 Greater London practices.Participants130 978 adults aged 50–79 years registered with their general practices on 1 January 2005, with no recorded history of dementia or care home residence.Primary and secondary outcome measuresA first recorded diagnosis of dementia and, where specified, subgroups of Alzheimer’s disease and vascular dementia during 2005–2013. The average annual concentrations during 2004 of nitrogen dioxide (NO2), particulate matter with a median aerodynamic diameter ≤2.5 µm (PM2.5) and ozone (O3) were estimated at 20×20 m resolution from dispersion models. Traffic intensity, distance from major road and night-time noise levels (Lnight) were estimated at the postcode level. All exposure measures were linked anonymously to clinical data via residential postcode. HRs from Cox models were adjusted for age, sex, ethnicity, smoking and body mass index, with further adjustments explored for area deprivation and comorbidity.Results2181 subjects (1.7%) received an incident diagnosis of dementia (39% mentioning Alzheimer’s disease, 29% vascular dementia). There was a positive exposure response relationship between dementia and all measures of air pollution except O3, which was not readily explained by further adjustment. Adults living in areas with the highest fifth of NO2concentration (>41.5 µg/m3) versus the lowest fifth (<31.9 µg/m3) were at a higher risk of dementia (HR=1.40, 95% CI 1.12 to 1.74). Increases in dementia risk were also observed with PM2.5, PM2.5specifically from primary traffic sources only and Lnight, but only NO2and PM2.5remained statistically significant in multipollutant models. Associations were more consistent for Alzheimer’s disease than vascular dementia.ConclusionsWe have found evidence of a positive association between residential levels of air pollution across London and being diagnosed with dementia, which is unexplained by known confounding factors.

Effects of air pollution on neurodegenerative diseases (Alzheimer's disease and vascular dementia) over Europe for present and future climate change scenarios

2021 ◽  
Author(s):  
Pedro Jiménez-Guerrero ◽  
Patricia Guzmán ◽  
Patricia Tarín-Carrasco ◽  
María Morales-Suarez-Varela
Keyword(s):  
Climate Change ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Neurodegenerative Diseases ◽  
Vascular Dementia ◽  
Future Climate ◽  
Population Projections ◽  
Future Climate Change ◽  
Climate Change Scenarios

&lt;p&gt;Air pollution has a serious impact on health and this problem will be aggravated under the action of climate change. This climate penalty can play an important role when trying to assess future impacts of air pollution on several pathologies. Among these diseases, the scientific literature is scarce when referring to the influence of atmospheric pollutants on neurodegenerative diseases for future climate change scenarios. Under this framework, this contribution evaluates the incidence of dementia (Alzheimer's disease and vascular dementia) occurring in Europe due to exposure of air pollution (essentially NO&lt;sub&gt;2&lt;/sub&gt; and PM2.5) for the present climatic period (1991-2010) and for a future climate change scenario (RCP8.5, 2031-2050). The GEMM methodology has been applied to climatic air pollution simulations using the chemistry/climate regional model WRF-Chem. Present population data were obtained from NASA's Center for Socioeconomic Data and Applications (SEDAC); while future population projections for the year 2050 were derived from the United Nations (UN) Department of Economic and Social Affairs-Population Dynamics.&lt;/p&gt;&lt;p&gt;Overall, the estimated incidence of Alzheimer's disease and vascular dementia associated to air pollution over Europe is 498,000 [95% confidence interval (95% CI) 348,600-647,400] and 314,000 (95% CI 257,500-401,900) new cases per year, respectively. An important increase in the future incidence is projected (around 72% for both types of dementia) when considering the effect of climate change together with the foreseen changes in the dynamics of population (expected aging of European population). The climate penalty has a limited effect on the total changes of Alzheimer's disease and vascular dementia (approx. 0.5%), since the large increase in new annual cases over southern Europe is offset by the decrease of the incidence associated to these pathologies over more northern countries, favored by an improvement of air pollution caused by the projected enhancement of rainfall.&lt;/p&gt;

Apolipoprotein E4, Gender, Body Mass Index, Inflammation, Insulin Resistance, and Air Pollution Interactions: Recipe for Alzheimer’s Disease Development in Mexico City Young Females

2021 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Suzanne M. de la Monte
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
High Risk ◽  
Mexico City ◽  
Cognitive Deficits ◽  
Central Nervous System Involvement ◽  
High Risk Group ◽  
Polycyclic Aromatic

Given the epidemiological trends of increasing Alzheimer’s disease (AD) and growing evidence that exposure and lifestyle factors contribute to AD risk and pathogenesis, attention should be paid to variables such as air pollution, in order to reduce rates of cognitive decline and dementia. Exposure to fine particulate matter (PM2.5) and ozone (O3) above the US EPA standards is associated with AD risk. Mexico City children experienced pre- and postnatal high exposures to PM2.5, O3, combustion-derived iron-rich nanoparticles, metals, polycyclic aromatic hydrocarbons, and endotoxins. Exposures are associated with early brain gene imbalance in oxidative stress, inflammation, innate and adaptive immune responses, along with epigenetic changes, accumulation of misfolded proteins, cognitive deficits, and brain structural and metabolic changes. The Apolipoprotein E (APOE) 4 allele, the most prevalent genetic risk for AD, plays a key role in the response to air pollution in young girls. APOE 4 heterozygous females with >75% to <94% BMI percentiles are at the highest risk of severe cognitive deficits (1.5–2 SD from average IQ). This review focused on the relationships between gender, BMI, systemic and neural inflammation, insulin resistance, hyperleptinemia, dyslipidemia, vascular risk factors, and central nervous system involvement in APOE4 urbanites exposed to PM2.5 and magnetite combustion-derived iron-rich nanoparticles that can reach the brain. APOE4 young female heterozygous carriers constitute a high-risk group for a fatal disease: AD. Multidisciplinary intervention strategies could be critical for prevention or amelioration of cognitive deficits and long-term AD progression in young individuals at high risk.

A Critical Proton MR Spectroscopy Marker of Alzheimer’s Disease Early Neurodegenerative Change: Low Hippocampal NAA/Cr Ratio Impacts APOE ε4 Mexico City Children and Their Parents

2021 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Antonieta Mora-Tiscareño ◽  
Gastón Melo-Sánchez ◽  
Joel Rodríguez-Díaz ◽  
Ricardo Torres-Jardón ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Mexico City ◽  
Density Functional ◽  
Fine Particulate Matter ◽  
Healthy Children ◽  
1H Mrs ◽  
Apoe Ε4 ◽  
The Right

Severe air pollution exposures produce systemic, respiratory, myocardial, and brain inflammation and Alzheimer’s disease (AD) hallmarks in clinically healthy children. We tested whether hippocampal metabolite ratios are associated with contrasting levels of air pollution, APOE, and body mass index (BMI) in paired healthy children and one parent sharing the same APOE alleles. We used 1H-MRS to interrogate bilateral hippocampal single-voxel in 57 children (12.45 ± 3.4 years) and their 48 parents (37.5 ± 6.78 years) from a low pollution city versus Mexico City (MC). NAA/Cr, Cho/Cr, and mI/Cr metabolite ratios were analyzed. The right hippocampus NAA/Cr ratio was significantly different between cohorts (p = 0.007). The NAA/Cr ratio in right hippocampus in controls versus APOE ε4 MC children and in left hippocampus in MC APOE ε4 parents versus their children was significantly different after adjusting for age, gender, and BMI (p = 0.027 and 0.01, respectively). The NAA/Cr ratio is considered reflective of neuronal density/functional integrity/loss of synapses/higher pTau burden, thus a significant decrease in hippocampal NAA/Cr ratios may constitute a spectral marker of early neurodegeneration in young urbanites. Decreases in NAA/Cr correlate well with cognitive function, behavioral symptoms, and dementia severity; thus, since the progression of AD starts decades before clinical diagnosis, our findings support the hypothesis that under chronic exposures to fine particulate matter and ozone above the standards, neurodegenerative processes start in childhood and APOE ε4 carriers are at higher risk. Gene and environmental factors are critical in the development of AD and the identification and neuroprotection of young urbanites at high risk must become a public health priority.

Air Pollution as Risk Factor for Mental Disorders: In Search for a Possible Link with Alzheimer’s Disease and Schizophrenia

2021 ◽  
Author(s):  
Luigi Attademo ◽  
Francesco Bernardini
Keyword(s):  
Mental Health ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Risk Factor ◽  
Air Pollutants ◽  
Epidemiological Studies ◽  
Increased Risk ◽  
The Central Nervous System

As a global problem that has increasingly been causing worldwide concern, air pollution poses a significant and serious environmental risk to health. Risks of cardiovascular and respiratory diseases, as well as various types of cancer, have been consistently associated with the exposure to air pollutants. More recently, various studies have also shown that the central nervous system is also attacked by air pollution. Air pollution appears to be strongly associated with a higher risk of cognitive defects, neurodevelopmental (e.g., schizophrenia) and neurodegenerative (e.g., Alzheimer’s disease) disorders. Subjects with schizophrenia, as well as subjects with Alzheimer’s disease, experience a variety of neuropsychological deficits and cognitive impairments. This determines an adverse effect on social and professional functioning, and it contributes to the long-term disease burden. However, no final conclusions have been drawn on the matter of the direct relationship between schizophrenia and Alzheimer’s disease. In recent years, the topic of urbanicity and mental health has become increasingly important. Urban exposure to environmental toxins and pollution is currently described as a reliable risk factor for schizophrenia and other psychoses, and it has been demonstrated more and more how exposure to air pollutants is associated with increased risk of dementia. Pathways by which air pollution can target and damage the brain, leading to an increased risk for developing schizophrenia and Alzheimer’s disease, are multiple and complex. Results from epidemiological studies suggest potential associations, but are still insufficient to confirm causality. Further studies are needed in order to verify this hypothesis. And if confirmed, the clinical implications could be of substantial relevance for both public and mental health.

Air Pollution, Combustion and Friction Derived Nanoparticles, and Alzheimer’s Disease in Urban Children and Young Adults

2021 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Angélica González-Maciel ◽  
Randy J. Kulesza ◽  
Luis Oscar González-González ◽  
Rafael Reynoso-Robles ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Young Adults ◽  
Particulate Matter ◽  
Mexico City ◽  
Neurofibrillary Tangle ◽  
Rapid Progression ◽  
Us Epa ◽  
Children And Young Adults

Exposures to fine particulate matter (PM2.5) and ozone (O3)≥US EPA standards are associated with Alzheimer’s disease (AD) risk. The projection of 13.8 million AD cases in the US by the year 2050 obligate us to explore early environmental exposures as contributors to AD risk and pathogenesis. Metropolitan Mexico City children and young adults have lifetime exposures to PM2.5 and O3, and AD starting in the brainstem and olfactory bulb is relentlessly progressing in the first two decades of life. Magnetite combustion and friction-derived nanoparticles reach the brain and are associated with early and progressive damage to the neurovascular unit and to brain cells. In this review: 1) we highlight the interplay environment/genetics in the AD development in young populations; 2) comment upon ApoE ε4 and the rapid progression of neurofibrillary tangle stages and higher suicide risk in youth; and 3) discuss the role of combustion-derived nanoparticles and brain damage. A key aspect of this review is to show the reader that air pollution is complex and that profiles change from city to city with common denominators across countries. We explore and compare particulate matter profiles in Mexico City, Paris, and Santiago in Chile and make the point of why we should invest in decreasing PM2.5 to at least our current US EPA standard. Multidisciplinary intervention strategies are critical for prevention or amelioration of cognitive deficits and AD progression and risk of suicide in young individuals. AD pathology evolving from childhood is threating the wellbeing of future generations.

Ozone, Particulate Matter, and Newly Diagnosed Alzheimer’s Disease: A Population-Based Cohort Study in Taiwan

2021 ◽  
Author(s):  
Chau-Ren Jung ◽  
Yu-Ting Lin ◽  
Bing-Fang Hwang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Cohort Study ◽  
Particulate Matter ◽  
Proportional Hazards ◽  
Newly Diagnosed ◽  
Hazards Model

Several studies with animal research associate air pollution in Alzheimer’s disease (AD) neuropathology, but the actual impact of air pollution on the risk of AD is unknown. Here, this study investigates the association between long-term exposure to ozone (O3) and particulate matter (PM) with an aerodynamic diameter equal to or less than 2.5 μm (PM2.5), and newly diagnosed AD in Taiwan. We conducted a cohort study of 95,690 individuals’ age ≥ 65 during 2001–2010. We obtained PM10 and O3 data from Taiwan Environmental Protection Agency during 2000–2010. Since PM2.5 data is only accessible entirely after 2006, we used the mean ratio between PM2.5 and PM10 during 2006–2010 (0.57) to estimate the PM2.5 concentrations from 2000 to 2005. A Cox proportional hazards model was used to evaluate the associations between O3 and PM2.5 at baseline and changes of O3 and PM2.5 during the follow-up period and AD. The adjusted HR for AD was weakly associated with a raised concentration in O3 at baseline per increase of 9.63 ppb (adjusted HR 1.06, 95% confidence interval (CI) 1.00–1.12). Further, we estimated a 211% risk of increase of AD per increase of 10.91 ppb in O3 over the follow-up period (95% CI 2.92–3.33). We found a 138% risk of increase of AD per increase of 4.34 μg/m3 in PM2.5 over the follow-up period (95% CI 2.21–2.56). These findings suggest long-term exposure to O3 and PM2.5 above the current US EPA standards are associated with increased the risk of AD.

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