Midlife milk consumption and substantia nigra neuron density at death

Abbott, Robert D.; Ross, G. Webster; Petrovitch, Helen; Masaki, Kamal; Launer, Lenore J.; Nelson, James S.; White, Lon R.; Tanner, Caroline M.

doi:10.1212/wnl.0000000000002254

Cited by 41 publications

(36 citation statements)

References 37 publications

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“…The contamination was traced to the use of chopped pineapple leaves from the plantations where heptachlor was in use to create a “wholesome” diet for the Hawaiian dairy herd . Earlier reports from the HAAS found a higher risk of clinical PD and lower substantia nigra neuron density at death in nonsmokers who were heavy consumers of milk . Heptachlor epoxide was also more commonly found in the brains of heavy milk consumers than in nondrinkers …”

Section: Discussionmentioning

confidence: 99%

“…Altogether, the evidence is persuasive that certain organochlorine pesticides may contribute to the cause of PD. In particular, heptachlor epoxide may be especially important in increasing the accumulation of α‐synuclein deposits in the brain in the form of Lewy pathology and in lowering substantia nigra neuron density . Although further validation is needed, it is important to avoid exposure to suspected compounds, especially heptachlor epoxide in the instances when it continues to be used, most commonly in developing countries .…”

Section: Discussionmentioning

confidence: 99%

“…3,24 Earlier reports from the HAAS found a higher risk of clinical PD and lower substantia nigra neuron density at death in nonsmokers who were heavy consumers of milk. 5,6 Heptachlor epoxide was also more commonly found in the brains of heavy milk consumers than in nondrinkers. 6 In addition to heptachlor epoxide, α-chlordane, and hexachlorobenzene were also important in Hawaiian agriculture.…”

Section: Discussionmentioning

confidence: 99%

“…Given that dairy products have been linked to clinical PD, documentation of the contamination of the milk supply in Hawaii with heptachlor epoxide is both unique and important. Recent findings from the HAAS also suggest that milk consumption is associated with early nigral neurodegeneration in nonsmoking men without PD and that the relationship is partly attributed to the coexistence of brain residues of heptachlor epoxide . Based on an expanded survey of brain organochlorine residues in the HAAS, using larger amounts of brain tissue and improved analytical procedures, the purpose of this study was to better characterize the association of heptachlor epoxide with Lewy pathology.…”

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confidence: 99%

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Association of brain heptachlor epoxide and other organochlorine compounds with lewy pathology

et al. 2018

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Background: Organochlorine pesticides are associated with an increased risk of Parkinson’s disease. A preliminary analysis from the Honolulu-Asia Aging Study suggested that heptachlor epoxide, a metabolite from an organochlorine pesticide extensively used in Hawaii, may be especially important. This was a cross sectional analysis to evaluate the association of heptachlor epoxide and other organochlorine compounds with Lewy pathology in an expanded survey of brain organochlorine residues from the longitudinal Honolulu-Asia Aging Study. Methods: Organochlorines were measured in frozen occipital or temporal lobes in 705 brains using gas chromatography with mass spectrometry. Lewy pathology was identified using hematoxylin and eosin- and α-synuclein immunochemistry-stained sections from multiple brain regions. Results: The prevalence of Lewy pathology was nearly doubled in the presence versus the absence of heptachlor epoxide (30.1% versus 16.3%, P < 0.001). Although associations with other compounds were weaker, hexachlorobenzene (P = 0.003) and α-chlordane (P = 0.007) were also related to Lewy pathology. Most of the latter associations, however, were a result of confounding from heptachlor epoxide. Neither compound was significantly related to Lewy pathology after adjustment for heptachlor epoxide. In contrast, the association of heptachlor epoxide with Lewy pathology remained significant after adjustments for hexachlorobenzene (P = 0.013) or α-chlordane (P = 0.005). Findings were unchanged after removal of cases of PD and adjustment for age and other characteristics. Conclusions: Organochlorine pesticides are associated with the presence of Lewy pathology in the brain, even after exclusion of PD cases. Although most of the association is through heptachlor epoxide, the role of other organochlorine compounds is in need of clarification.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Association of brain heptachlor epoxide and other organochlorine compounds with lewy pathology

et al. 2018

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“…Much research has gone into obtaining new prospectively-collected data (e.g., The Parkinson Progression Marker Initiative Marek, 2011), as well as examining archived biofluid and tissue specimens [e.g., Honolulu Asian Aging Study (Abbott et al, 2016)]. However, much still remains to be desired.…”

Section: Future Directionsmentioning

confidence: 99%

Commentary: Aiming for Study Comparability in Parkinson's Disease: Proposal for a Modular Set of Biomarker Assessments to be Used in Longitudinal Studies

Alamri

MacAskill

Anderson

2017

Front. Aging Neurosci.

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Environment, lifestyle, and Parkinson's disease: Implications for prevention in the next decade

2019

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There is evidence from observational studies for a role of a number of environmental exposures and lifestyle habits in modulating the risk for Parkinson's disease. Environmental and lifestyle associations, if causal, represent opportunities for Parkinson's disease prevention or disease modification at individual and population levels. In the past decade, additional evidence has been published that improves causal inference and/or enhances our understanding of the complexity of these associations. A number of gene–environment interactions have been elucidated, and our understanding of the roles of physical activity, pesticide and other chemical exposures, dietary habits, emotional stress, head injury, and smoking has been refined. In the next decade, better techniques will help us to close the gaps in our knowledge, including taking into account Parkinson's disease heterogeneity and gene and risk factor interactions in observational studies. To do this, larger datasets, global consortia, genomewide environment interaction studies, prospective studies throughout the lifespan, and improvements in the methodology of clinical trials of physical activity will be key. Despite the caveats of observational studies, a number of low‐risk and potentially high‐yield recommendations for lifestyle modification could be made to minimize the individual and societal burdens of Parkinson's disease, including dietary modifications, increasing physical activity, and head injury avoidance. Furthermore, a reduction in pesticide use could have a major impact on global health related to and beyond Parkinson's disease. Given the increasing prevalence of this disorder, formulating and promoting these recommendations should be a high priority. © 2019 International Parkinson and Movement Disorder Society

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Midlife milk consumption and substantia nigra neuron density at death

Abstract: Milk intake is associated with SN neuron loss in decedent brains unaffected by PD. Whether contamination of milk with organochlorine pesticides has a role in SN neurodegeneration warrants further study.

Cited by 41 publications

References 37 publications

Association of brain heptachlor epoxide and other organochlorine compounds with lewy pathology

Association of brain heptachlor epoxide and other organochlorine compounds with lewy pathology

Commentary: Aiming for Study Comparability in Parkinson's Disease: Proposal for a Modular Set of Biomarker Assessments to be Used in Longitudinal Studies

Environment, lifestyle, and Parkinson's disease: Implications for prevention in the next decade

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