Might Lifetime Exposure to Lead Confound the Association Between Hearing Impairment and Incident Dementia?

Might Lifetime Exposure to Lead Confound the Association Between Hearing Impairment and Incident... Lead exposure, Lead poisoning, Environmental pollutants, Tetraethyl lead, Hearing loss The methodologically rigorous study by Deal and colleagues, “Hearing Impairment and Incident Dementia and Cognitive Decline in Older Adults” (1), is an important contribution to the burgeoning evidence that hearing impairment (HI) is associated with increased risk of incident dementia (2). Deal and colleagues provide three potential mechanisms through which HI may be causally associated with dementia. However, the authors cautiously note that it “may be that both HI and dementia are caused by a common underlying pathology such as vascular disease.” ((1), p. 707) I hypothesize that lifetime exposure to lead may be an important “common underlying pathology” that is causally associated with both HI and dementia. To put the historic levels of lead exposure in context, it is helpful to compare levels found in the recent, well-publicized Flint Michigan drinking water crisis to those found in the 1970s before the complete phase-out of leaded gasoline. In Flint Michigan in 2014, tainted drinking water from corrosion in the lead pipes resulted in unacceptably high blood lead levels (BLL), with 5% of children under 6 years having BLL ≥5 µg/dL and 0.8% having BLL ≥10 µg/dL (3). In comparison, in the late 1970s, 99.8% of U.S. children under 6 years had BLL ≥5 µg/dL, 88.2% had BLL ≥10 µg/dL and 24.7% had BLL ≥20 µg/dL, with a mean for the whole U.S. population of 13.1 μg/dL (4), largely due to pollutants caused by tetraethyl lead additives in gasoline. Hearing loss has been linked to higher levels of blood (5,6) and bone (7) lead. In a population-based study of U.S. adolescents, the odds of high frequency hearing loss was double among those with BLL > 2 μg/dL in comparison to those with BLL < 1 μg/dL, even after many potential confounders were taken into account (5). In a study of lead battery workers in Iran, individuals with BLL between 10 and 19 μg/dL had triple the odds of high frequency hearing loss in comparison to those with BLL < 10 μg/dL (8). In a population-based U.S. sample, an exposure–response relationship was shown between level of BLL and HI, even after adjustments for other important risk factors for hearing loss (6). Cumulative lifetime exposure to lead, as measured by bone lead levels, is associated with higher odds of hearing loss and faster declines in hearing thresholds (7). Lifetime exposure to lead is also associated with accelerated cognitive decline in studies of occupationally exposed workers (9) and in a community cohort of nonoccupationally exposed older men (10,11). An expert panel funded by the National Institute of Health concluded that “sufficient evidence exists to conclude that there is an association between lead dose and decrements in cognitive function in adults.” ((9), p. 489). Experimental studies with animals have demonstrated that lead exposure can damage receptor cells in the inner ear, impair the function of auditory neurons (5–7), and increase amyloidogenesis and senile plaque deposition in primates (12). We have previously proposed that the unexpected substantial decline in the prevalence of HI in the U.S. adult population, aged 20–69, between 1999 and 2012 (13), and the dramatic decline in the incidence and age-adjusted prevalence of dementia in the developed world, may be partially due to lower lifetime lead exposure in later birth cohorts (14,15). A recent Lancet commissioned review (16), drawing upon the study by Deal et al. (1) among others, suggested that hearing loss is the leading preventable cause of dementia. This implies that the relationship between hearing loss and dementia is causal and therefore potentially modifiable with midlife management of hearing loss. An alternate plausible explanation is that lifetime exposure to the formerly ubiquitous neurotoxin, lead, may be causally associated with both hearing loss and dementia. In order to test this hypothesis, future studies examining the association between hearing loss and incident dementia could investigate whether adjustment for cumulative lifetime lead exposure, as measured by tibia bone lead level, substantially attenuates the hearing loss-dementia relationship. Funding The author would like to gratefully acknowledge support received from the Sandra Rotman Endowed Chair in Social Work at the University of Toronto. Conflict of Interest None reported. References 1. Deal JA , Betz J , Jaffe K et al. Hearing impairment and incident dementia and cognitive decline in older adults: the health ABC study . J Gerontol A Biol Sci Med Sci . 2017 ; 72 : 703 – 709 . doi: 10.1093/gerona/glw069 Google Scholar PubMed 2. Thomson RS , Auduong P , Miller AT , Gurgel RK . Hearing loss as a risk factor for dementia: a systematic review . Laryngoscope Investig Otolaryngol . 2017 ; 2 : 69 – 79 . doi: 10.1002/lio2.65 Google Scholar CrossRef Search ADS PubMed 3. Kennedy C , Yard E , Dignam T et al. Blood lead levels among children aged <6 years - Flint, Michigan, 2013–2016 . MMWR Morb Mortal Wkly Rep . 2016;65 . doi: 10.15585/mmwr.mm6525e1 4. Pirkle JL , Brody DJ , Gunter EW et al. The decline in blood lead levels in the United States. The national health and nutrition examination surveys (NHANES) . JAMA . 1994 ; 272 : 284 – 291 .doi:10.1001/jama.1994.03520040046039 Google Scholar CrossRef Search ADS PubMed 5. Shargorodsky J , Curhan SG , Henderson E , Eavey R , Curhan GC . Heavy metals exposure and hearing loss in US adolescents . Arch Otolaryngol Head Neck Surg . 2011 ; 137 : 1183 – 1189 . doi: 10.1001/archoto.2011.202 Google Scholar CrossRef Search ADS PubMed 6. Choi YH , Hu H , Mukherjee B , Miller J , Park SK . Environmental cadmium and lead exposures and hearing loss in U.S. adults: the national health and nutrition examination survey, 1999 to 2004 . Environ Health Perspect . 2012 ; 120 : 1544 – 1550 . doi: 10.1289/ehp.1104863 Google Scholar CrossRef Search ADS PubMed 7. Park SK , Elmarsafawy S , Mukherjee B et al. Cumulative lead exposure and age-related hearing loss: the VA normative aging study . Hear Res . 2010 ; 269 : 48 – 55 . doi: 10.1016/j.heares.2010.07.004 Google Scholar CrossRef Search ADS PubMed 8. Ghiasvand M , Mohammadi S , Roth B , Ranjbar M . The relationship between occupational exposure to lead and hearing loss in a cross-sectional survey of Iranian workers . Front Public Health . 2016 ; 4 : 19 . doi: 10.3389/fpubh.2016.00019 Google Scholar CrossRef Search ADS PubMed 9. Shih RA , Hu H , Weisskopf MG , Schwartz BS . Cumulative lead dose and cognitive function in adults: a review of studies that measured both blood lead and bone lead . Environ Health Perspect . 2007 ; 115 : 483 – 492 . doi: 10.1289/ehp.9786 Google Scholar CrossRef Search ADS PubMed 10. Weisskopf MG , Proctor SP , Wright RO et al. Cumulative lead exposure and cognitive performance among elderly men . Epidemiology . 2007 ; 18 : 59 – 66 . doi: 10.1097/01.ede.0000248237.35363.29 Google Scholar CrossRef Search ADS PubMed 11. Weisskopf MG , Wright RO , Schwartz J et al. Cumulative lead exposure and prospective change in cognition among elderly men: the VA normative aging study . Am J Epidemiol . 2004 ; 160 : 1184 – 1193 . doi: 10.1093/aje/ Google Scholar CrossRef Search ADS PubMed 12. Bakulski KM , Rozek LS , Dolinoy DC , Paulson HL , Hu H . Alzheimer’s disease and environmental exposure to lead: the epidemiologic evidence and potential role of epigenetics . Curr Alzheimer Res . 2012 ; 9 : 563 – 573 .doi:10.2174/156720512800617991 Google Scholar CrossRef Search ADS PubMed 13. Hoffman HJ , Dobie RA , Losonczy KG , Themann CL , Flamme , GA . Declining prevalence of hearing loss in US adults aged 20 to 69 years . JAMA Otolaryngol Head Neck Surg . 2016;143:274–285 . doi: 10.1001/jamaoto.2016.3527 14. Fuller-Thomson E . The reduction in the age-adjusted prevalence of hearing impairment in the USA: an unexpected dividend of phasing out leaded gasoline ? JAMA Otolaryngol Head Neck Surg . 2017;143:956–957 .doi:10.1001/jamaoto.2017.0684 15. Fuller-Thomson E , Jopling SA . Could the adoption of unleaded gasoline in the 1970s play a role in the precipitous decline in dementia prevalence ? JAMA Intern Med . 2017 ; 177 : 892 – 893 . doi: 10.1001/jamainternmed.2017.1074 Google Scholar CrossRef Search ADS PubMed 16. Livingston G , Sommerlad A , Orgeta V et al. Dementia prevention, intervention, and care . Lancet . 2017;390:2673–2734 . doi: 10.1016/ S0140-6736(17)31363–6 © The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences Oxford University Press

Might Lifetime Exposure to Lead Confound the Association Between Hearing Impairment and Incident Dementia?

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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1079-5006
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1758-535X
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10.1093/gerona/glx238
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Abstract

Lead exposure, Lead poisoning, Environmental pollutants, Tetraethyl lead, Hearing loss The methodologically rigorous study by Deal and colleagues, “Hearing Impairment and Incident Dementia and Cognitive Decline in Older Adults” (1), is an important contribution to the burgeoning evidence that hearing impairment (HI) is associated with increased risk of incident dementia (2). Deal and colleagues provide three potential mechanisms through which HI may be causally associated with dementia. However, the authors cautiously note that it “may be that both HI and dementia are caused by a common underlying pathology such as vascular disease.” ((1), p. 707) I hypothesize that lifetime exposure to lead may be an important “common underlying pathology” that is causally associated with both HI and dementia. To put the historic levels of lead exposure in context, it is helpful to compare levels found in the recent, well-publicized Flint Michigan drinking water crisis to those found in the 1970s before the complete phase-out of leaded gasoline. In Flint Michigan in 2014, tainted drinking water from corrosion in the lead pipes resulted in unacceptably high blood lead levels (BLL), with 5% of children under 6 years having BLL ≥5 µg/dL and 0.8% having BLL ≥10 µg/dL (3). In comparison, in the late 1970s, 99.8% of U.S. children under 6 years had BLL ≥5 µg/dL, 88.2% had BLL ≥10 µg/dL and 24.7% had BLL ≥20 µg/dL, with a mean for the whole U.S. population of 13.1 μg/dL (4), largely due to pollutants caused by tetraethyl lead additives in gasoline. Hearing loss has been linked to higher levels of blood (5,6) and bone (7) lead. In a population-based study of U.S. adolescents, the odds of high frequency hearing loss was double among those with BLL > 2 μg/dL in comparison to those with BLL < 1 μg/dL, even after many potential confounders were taken into account (5). In a study of lead battery workers in Iran, individuals with BLL between 10 and 19 μg/dL had triple the odds of high frequency hearing loss in comparison to those with BLL < 10 μg/dL (8). In a population-based U.S. sample, an exposure–response relationship was shown between level of BLL and HI, even after adjustments for other important risk factors for hearing loss (6). Cumulative lifetime exposure to lead, as measured by bone lead levels, is associated with higher odds of hearing loss and faster declines in hearing thresholds (7). Lifetime exposure to lead is also associated with accelerated cognitive decline in studies of occupationally exposed workers (9) and in a community cohort of nonoccupationally exposed older men (10,11). An expert panel funded by the National Institute of Health concluded that “sufficient evidence exists to conclude that there is an association between lead dose and decrements in cognitive function in adults.” ((9), p. 489). Experimental studies with animals have demonstrated that lead exposure can damage receptor cells in the inner ear, impair the function of auditory neurons (5–7), and increase amyloidogenesis and senile plaque deposition in primates (12). We have previously proposed that the unexpected substantial decline in the prevalence of HI in the U.S. adult population, aged 20–69, between 1999 and 2012 (13), and the dramatic decline in the incidence and age-adjusted prevalence of dementia in the developed world, may be partially due to lower lifetime lead exposure in later birth cohorts (14,15). A recent Lancet commissioned review (16), drawing upon the study by Deal et al. (1) among others, suggested that hearing loss is the leading preventable cause of dementia. This implies that the relationship between hearing loss and dementia is causal and therefore potentially modifiable with midlife management of hearing loss. An alternate plausible explanation is that lifetime exposure to the formerly ubiquitous neurotoxin, lead, may be causally associated with both hearing loss and dementia. In order to test this hypothesis, future studies examining the association between hearing loss and incident dementia could investigate whether adjustment for cumulative lifetime lead exposure, as measured by tibia bone lead level, substantially attenuates the hearing loss-dementia relationship. Funding The author would like to gratefully acknowledge support received from the Sandra Rotman Endowed Chair in Social Work at the University of Toronto. Conflict of Interest None reported. References 1. Deal JA , Betz J , Jaffe K et al. Hearing impairment and incident dementia and cognitive decline in older adults: the health ABC study . J Gerontol A Biol Sci Med Sci . 2017 ; 72 : 703 – 709 . doi: 10.1093/gerona/glw069 Google Scholar PubMed 2. Thomson RS , Auduong P , Miller AT , Gurgel RK . Hearing loss as a risk factor for dementia: a systematic review . Laryngoscope Investig Otolaryngol . 2017 ; 2 : 69 – 79 . doi: 10.1002/lio2.65 Google Scholar CrossRef Search ADS PubMed 3. Kennedy C , Yard E , Dignam T et al. Blood lead levels among children aged <6 years - Flint, Michigan, 2013–2016 . MMWR Morb Mortal Wkly Rep . 2016;65 . doi: 10.15585/mmwr.mm6525e1 4. Pirkle JL , Brody DJ , Gunter EW et al. The decline in blood lead levels in the United States. The national health and nutrition examination surveys (NHANES) . JAMA . 1994 ; 272 : 284 – 291 .doi:10.1001/jama.1994.03520040046039 Google Scholar CrossRef Search ADS PubMed 5. Shargorodsky J , Curhan SG , Henderson E , Eavey R , Curhan GC . Heavy metals exposure and hearing loss in US adolescents . Arch Otolaryngol Head Neck Surg . 2011 ; 137 : 1183 – 1189 . doi: 10.1001/archoto.2011.202 Google Scholar CrossRef Search ADS PubMed 6. Choi YH , Hu H , Mukherjee B , Miller J , Park SK . Environmental cadmium and lead exposures and hearing loss in U.S. adults: the national health and nutrition examination survey, 1999 to 2004 . Environ Health Perspect . 2012 ; 120 : 1544 – 1550 . doi: 10.1289/ehp.1104863 Google Scholar CrossRef Search ADS PubMed 7. Park SK , Elmarsafawy S , Mukherjee B et al. Cumulative lead exposure and age-related hearing loss: the VA normative aging study . Hear Res . 2010 ; 269 : 48 – 55 . doi: 10.1016/j.heares.2010.07.004 Google Scholar CrossRef Search ADS PubMed 8. Ghiasvand M , Mohammadi S , Roth B , Ranjbar M . The relationship between occupational exposure to lead and hearing loss in a cross-sectional survey of Iranian workers . Front Public Health . 2016 ; 4 : 19 . doi: 10.3389/fpubh.2016.00019 Google Scholar CrossRef Search ADS PubMed 9. Shih RA , Hu H , Weisskopf MG , Schwartz BS . Cumulative lead dose and cognitive function in adults: a review of studies that measured both blood lead and bone lead . Environ Health Perspect . 2007 ; 115 : 483 – 492 . doi: 10.1289/ehp.9786 Google Scholar CrossRef Search ADS PubMed 10. Weisskopf MG , Proctor SP , Wright RO et al. Cumulative lead exposure and cognitive performance among elderly men . Epidemiology . 2007 ; 18 : 59 – 66 . doi: 10.1097/01.ede.0000248237.35363.29 Google Scholar CrossRef Search ADS PubMed 11. Weisskopf MG , Wright RO , Schwartz J et al. Cumulative lead exposure and prospective change in cognition among elderly men: the VA normative aging study . Am J Epidemiol . 2004 ; 160 : 1184 – 1193 . doi: 10.1093/aje/ Google Scholar CrossRef Search ADS PubMed 12. Bakulski KM , Rozek LS , Dolinoy DC , Paulson HL , Hu H . Alzheimer’s disease and environmental exposure to lead: the epidemiologic evidence and potential role of epigenetics . Curr Alzheimer Res . 2012 ; 9 : 563 – 573 .doi:10.2174/156720512800617991 Google Scholar CrossRef Search ADS PubMed 13. Hoffman HJ , Dobie RA , Losonczy KG , Themann CL , Flamme , GA . Declining prevalence of hearing loss in US adults aged 20 to 69 years . JAMA Otolaryngol Head Neck Surg . 2016;143:274–285 . doi: 10.1001/jamaoto.2016.3527 14. Fuller-Thomson E . The reduction in the age-adjusted prevalence of hearing impairment in the USA: an unexpected dividend of phasing out leaded gasoline ? JAMA Otolaryngol Head Neck Surg . 2017;143:956–957 .doi:10.1001/jamaoto.2017.0684 15. Fuller-Thomson E , Jopling SA . Could the adoption of unleaded gasoline in the 1970s play a role in the precipitous decline in dementia prevalence ? JAMA Intern Med . 2017 ; 177 : 892 – 893 . doi: 10.1001/jamainternmed.2017.1074 Google Scholar CrossRef Search ADS PubMed 16. Livingston G , Sommerlad A , Orgeta V et al. Dementia prevention, intervention, and care . Lancet . 2017;390:2673–2734 . doi: 10.1016/ S0140-6736(17)31363–6 © The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

The Journals of Gerontology Series A: Biomedical Sciences and Medical SciencesOxford University Press

Published: Feb 26, 2018

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