Table 1.

Epidemiological studies summarizing association between endogenous estrogen, hormonal replacement therapy, phthalates, polychlorinated biphenyls, cadmium, arsenic and manganese and neurodegenerative diseases—Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and dementia.

Study Reference	EDC	Year	Epidemiological Study Type	Effect on Brain	Brain Disease
Manly et al., 2000	Endogenous estrogen	2000	Case-control	Lower estradiol levels in women associated with greater risk of AD.	AD
Geerlings et al., 2001	Endogenous estrogen	2001	Prospective cohort	Longer exposure to endogenous estrogen associated with AD and dementia.	Dementia and AD
Schupf et al., 2006	Endogenous estrogen	2006	Prospective-cohort	Women with low bioavailable estrogen were more likely to develop AD.	AD
De Jong et al., 2012	Endogenous estrogen	2012	Case-Control	Longer reproductive time-span and exposure to endogenous estrogen decreases ALS risk.	ALS
Fox et al., 2013	Endogenous estrogen	2013	Retrospective cohort study	Longer duration of endogenous estrogen exposure may have a protective effect against AD risk.	AD
Cereda et al., 2013	Endogenous estrogen	2013	Cross-sectional	Age of PD onset was positively associated with duration of exposure to endogenous estrogens.	PD
Shumaker et al., 2003	Hormonal replacement therapy	2003	Clinical trial	Estrogen progestin HRT increased risk for dementia and did not prevent cognitive impairment.	Dementia
Shumaker et al., 2004	Hormonal replacement therapy	2004	Clinical trial	Estrogen only HRT increased risk of dementia and cognitive impairment.	Dementia
Shao et al., 2012	Hormonal replacement therapy	2012	Cohort study	Increased Alzheimer’s disease risk amongst women who used HRT more than five years after menopause, but observed a decreased risk of AD if used within five years of menopause.	AD
Lundin et al., 2014	Hormonal replacement therapy	2014	Cohort study	Increased in PD risk observed depending on type of hormonal therapy.	PD
Weisskopf et al., 2012	Polychlorinated biphenyls	2012	Nested case-control	PCB exposure not associated with PD development.	PD
Steenland et al., 2006	Polychlorinated biphenyls	2006	Retrospective mortality study	In PCB exposed plant workers, higher death rates from PD were observed in women.	PD
Hatcher-Martin et al., 2012	Polychlorinated biphenyls	2012	Case-control	In post-mortem brain tissue from PD, AD, and controls, PCB levels were higher in PD brain tissue.	PD
Roos et al., 2013	Cadmium	2013	Cross-sectional	Elevated heavy metals, including cadmium, were higher in ALS patients.	ALS
Komatsu et al., 2011	Cadmium	2011	Case-control	Elevated cadmium hair levels were associated with Parkinson-like symptoms.	PD
Park et al., 2014	Arsenic	2014	Cross-sectional	No difference in serum arsenic levels in AD patients and controls.	AD
Hozumi et al., 2011	Manganese	2011	Cross-sectional	Higher levels of manganese found among PD patients.	PD
Koc et al., 2015	Manganese	2015	Cross-sectional	Higher manganese levels found in hair samples of AD patients compared to controls.	AD
Miyake et al., 2011	Manganese	2011	Case-control	In PD patients, no association found with increased manganese intake.	PD
Roos et al., 2013	Manganese	2013	Case-control	Elevated manganese levels observed in ALS patients.	ALS
Kumudini et al., 2014	Manganese	2014	Case-control	No association between blood manganese levels in PD patients’ vs. controls.	PD
Garzillo et al., 2014	Manganese	2014	Case-control	No association between blood manganese levels in ALS patients’ vs. controls.	ALS
Kihira et al., 2015	Manganese	2015	Case-control	Elevated manganese levels in hair observed in ALS patients’ vs. controls.	ALS
Arain et al., 2015	Manganese	2015	Case-control	Higher levels of manganese and aluminum in those suffering from neurodegenerative disease.	Neurodegenerative disease.
Baker et al., 2015	Manganese	2015	Prospective cohort	Low level manganese exposure causes sub-clinical brain changes before symptoms occur.	Neurodegenerative disease