Alzheimer disease starts in childhood in polluted Metropolitan Mexico City. A major health crisis in progress

Calderón‐Garcidueñas, Lilian; Torres‐Jardón, Ricardo; Kulesza, Randy J.; Mansour, Yusra; González‐González, Luis Oscar; González-Maciel, Angélica; Reynoso-Robles, Rafael; Mukherjee, Partha S.

doi:10.1016/j.envres.2020.109137

Cited by 68 publications

(53 citation statements)

References 133 publications

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“…The authors also emphasized the brain substrates supporting dual-task gait performance in amnestic and non-amnestic MCI subtypes were different, a key finding potentially very relevant for our MMC populations with evolving cognitive domain deficits and significant differences in PM 2.5 exposures and portals of entry of fine PM and nanoparticles to the brain. 36 , 37 , 72 , 96 , 105 , 106 Beauchet et al, 107 put forward a biologically plausible explanation for the correlation between greater subvolumes of the somatosensory cortex and hippocampus reported in fallers compared to non-fallers: a possible brain compensatory mechanism involving spatial navigation and integration of sensory information. Indeed, in explaining increased gain in the auditory pathway (measured as brainstem auditory evoked potentials) in MMC residents we strongly supported compensatory plasticity, neuroinflammation, and AD continuum as strong players in MMC residents.…”

Section: Discussionmentioning

confidence: 99%

“…The key question to be asked for Metropolitan Mexico City residents is why are we seen gait and balance dysfunction in seemingly healthy young adults 21.04±5.76y in the setting of cognitive deficits involving 55% of the population age 23.9±2.8y and MoCA dementia scores (≤23) in 22.38±7.7 y olds? 36 , 37 These are MMC residents with abnormal brainstem auditory evoked potentials 38 and those with extensive olfactory bulb neurovascular unit damage with evidence of both Alzheimer and Parkinson’s diseases. 110 , 111 Cognitive deficits in young MMC subjects progressively targeted Visuospatial, Executive, Language, and Memory domains, body mass index (BMI) impacted total scores negatively and age drove down Executive, Visuospatial, and Language index scores.…”

Section: Discussionmentioning

confidence: 99%

“… 110 , 111 Cognitive deficits in young MMC subjects progressively targeted Visuospatial, Executive, Language, and Memory domains, body mass index (BMI) impacted total scores negatively and age drove down Executive, Visuospatial, and Language index scores. 36 , 37 Are the MMC residents gait dysfunction and the cognitive deficits at a young age a surprise? No.…”

Section: Discussionmentioning

confidence: 99%

“…Given these findings we are concerned young Metropolitan Mexico City (MMC) residents exposed to concentrations of fine particulate matter (PM 2.5 ) above the United States Environmental Protection Agency (USEPA) standard and in conjunction with a historical documentation of Alzheimer pathology progressive changes 32 are showing the Montreal Cognitive Assessment (MoCA) scores in the published range of mild cognitive impairment and dementia. 36 , 37 MMC clinically healthy children have shown abnormal findings in phoneme recognition, finger to nose dysmetria, gait deviation, Romberg’s test positivity, fluid and crystallized cognition deficits and prefrontal white matter hyperintense lesions. 42 , 43 …”

Section: Introductionmentioning

confidence: 99%

“… 32 , 34 The Montreal Cognitive Assessment version 7, translated into Spanish, was our selected instrument. 36 , 37 MoCA covers several cognitive domains including episodic memory, language, attention, orientation, visuospatial and executive functions and has been validated in Mexican populations. 49 , 50 , 51 , 52 , 53…”

Section: Introductionmentioning

confidence: 99%

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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

Calderón‐Garcidueñas

Torres-Solorio

Kulesza

et al. 2020

Environmental Research

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

Calderón‐Garcidueñas

Torres-Solorio

Kulesza

et al. 2020

Environmental Research

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Association Between Ambient Air Pollution and Amyloid Positron Emission Tomography Positivity in Older Adults With Cognitive Impairment

et al. 2021

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IMPORTANCE Amyloid-β (Aβ) deposition is a feature of Alzheimer disease (AD) and may be promoted by exogenous factors, such as ambient air quality.OBJECTIVE To examine the association between the likelihood of amyloid positron emission tomography (PET) scan positivity and ambient air quality in individuals with cognitive impairment. DESIGN, SETTING, AND PARTICIPANTSThis cross-sectional study used data from the Imaging Dementia-Evidence for Amyloid Scanning Study, which included more than 18 000 US participants with cognitive impairment who received an amyloid PET scan with 1 of 3 Aβ tracers (fluorine 18 [ 18 F]-labeled florbetapir, 18 F-labeled florbetaben, or 18 F-labeled flutemetamol) between February 16, 2016, and January 10, 2018. A sample of older adults with mild cognitive impairment (MCI) or dementia was selected.EXPOSURES Air pollution was estimated at the patient residence using predicted fine particulate matter (PM 2.5 ) and ground-level ozone (O 3 ) concentrations from the Environmental Protection Agency Downscaler model. Air quality was estimated at 2002 to 2003 (early, or approximately 14 [range, 13-15] years before amyloid PET scan) and 2015 to 2016 (late, or approximately 1 [range, 0-2] years before amyloid PET scan).MAIN OUTCOMES AND MEASURES Primary outcome measure was the association between air pollution and the likelihood of amyloid PET scan positivity, which was measured as odds ratios (ORs) and marginal effects, adjusting for demographic, lifestyle, and socioeconomic factors and medical comorbidities, including respiratory, cardiovascular, cerebrovascular, psychiatric, and neurological conditions. RESULTSThe data set included 18 178 patients, of which 10 991 (60.5%) had MCI and 7187 (39.5%) had dementia (mean [SD] age, 75.8 [6.3] years; 9333 women [51.3%]). Living in areas with higher estimated biennial PM 2.5 concentrations in 2002 to 2003 was associated with a higher likelihood of amyloid PET scan positivity (adjusted OR, 1.10; 95% CI, 1.05-1.15; z score = 3.93; false discovery rate [FDR]-corrected P < .001; per 4-μg/m 3 increments). Results were similar for 2015 to 2016 data (OR, 1.15; 95% CI, 1.05-1.26, z score = 3.14; FDR-corrected P = .003). An average marginal effect (AME) of +0.5% (SE = 0.1%; z score, 3.93; 95% CI, 0.3%-0.7%; FDR-corrected P < .001) probability of amyloid PET scan positivity for each 1-μg/m 3 increase in PM 2.5 was observed for 2002 to 2003, whereas an AME of +0.8% (SE = 0.2%; z score = 3.15; 95% CI, 0.3%-1.2%; FDR-corrected P = .002) probability was observed for 2015 to 2016. Post hoc analyses showed no effect modification by sex (2002-2003: interaction term β = 1.01 [95% CI, 0.99-1.04; z score = 1.13; FDR-corrected P = .56]; 2015-2016: β = 1.02 [95% CI, 0.98-1.07; z score = 0.91; FDR-corrected P = .56]) or clinical stage (2002-2003: interaction term β = 1.01 [95% CI, 0.99-1.03; z score = 0.77; FDR-corrected P = .58]; 2015-2016: β = 1.03; 95% CI, 0.99-1.08; z score = 1.46; FDR-corrected P = .47]). Exposure to higher O 3 concentrations was not associated with amyl...

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Role of the Exposome in Neurodegenerative Disease: Recent Insights and Future Directions

Sakowski,

Koubek,

Chen

et al. 2024

Annals of Neurology

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Neurodegenerative diseases are increasing in prevalence and place a significant burden on society. The causes are multifactorial and complex, and increasing evidence suggests a dynamic interplay between genes and the environment, emphasizing the importance of identifying and understanding the role of lifelong exposures, known as the exposome, on the nervous system. This review provides an overview of recent advances toward defining neurodegenerative disease exposomes, focusing on Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. We present the current state of the field based on emerging data, elaborate on key themes and potential mechanisms, and conclude with limitations and future directions. ANN NEUROL 2024

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Alzheimer disease starts in childhood in polluted Metropolitan Mexico City. A major health crisis in progress

Cited by 68 publications

References 133 publications

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

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

Association Between Ambient Air Pollution and Amyloid Positron Emission Tomography Positivity in Older Adults With Cognitive Impairment

Role of the Exposome in Neurodegenerative Disease: Recent Insights and Future Directions

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