Repeated exposure to pesticides increases Alzheimers disease risk

Repeated exposure to pesticides, such as occurs with occupational use, is associated with an increase in the risk for Alzheimers disease (AD) in late life, according to an observational study published in the May issue of Neurology.

The researchers, led by Kathleen M. Hayden, PhD, from Duke University Medical Center, Durham, North Carolina, used data from the Cache County Study of Memory Health and Aging and found associations between occupational pesticide exposure and both dementia and AD.

Dr. Hayden told Medscape Neurology that the clinical implications of the study are not yet clear. "This is an observational study and it suggests an association from repeated pesticide use. Further study is needed to determine if there is a causal link," she noted. "Ideally, pesticides should be studied in a setting where they are routinely used and the exact exposures can be verified, such as in an agricultural study."

Pesticides and Dementia

Commonly used organophosphate and organochlorine pesticides inhibit acetylcholinesterase at synapses in the somatic, autonomic, and central nervous systems and therefore may have lasting effects on the nervous system, the study authors write. Few studies, though, have examined the relationship of pesticide exposure and risk for dementia or AD, they note.

Dr. Hayden and her team sought to examine this relationship by studying residents of an agricultural community in Cache County, Utah.

"The Cache County Study of Memory Health and Aging is a longitudinal population-based cohort study designed to study environmental and genetic risk factors for Alzheimers disease," Dr. Hayden told Medscape Neurology in an interview.

During the 14 plus years of the study, information was collected from participants regarding a wide range of factors that potentially modify the risk for AD, she said. "We were prompted by a colleague at Duke interested in organophosphates, and so we decided to look at the effects of occupational exposures to pesticides in the cohort."

Individuals 65 years and older as of January 1995 were invited to participate in the study. The participants completed detailed occupational history questionnaires that included information about exposures to various types of pesticides. The participants cognitive status was assessed at study entry and at 3, 7, and 10 years. The average duration of follow-up was 7.2 years.

Of the 3084 individuals without dementia at baseline, 572 reported some pesticide exposure. Significantly more men than women reported pesticide exposure (P < .0001), and more than 40% of those exposed reported farming as the primary occupation for most of their working lives.

Those with pesticide exposure had more years of education (P < .01) but were similar in age.

Of the 572 individuals reporting pesticide exposure, 316 were exposed to organophosphates, 256 were exposed to organochlorines, 25 were exposed to carbamates, and 28 reported exposure to methyl bromides.

The investigators found that 500 individuals developed incident dementia, and of these, 344 had a primary or secondary diagnosis of AD. They also found that 108 individuals who reported exposure to pesticides were later diagnosed as having dementia.

After adjusting for baseline age (centered at 65 years of age), education, and APOE ε4 status, the study showed an increased risk for dementia in those exposed to any pesticide (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.09 – 1.76). The risk for AD was similar (HR, 1.42; 95% CI, 1.06 – 1.91).

When the investigators looked at the association between risk for incident dementia or AD and specific pesticides, they found that the risk for dementia associated with exposure to organophosphates was increased among those exposed (HR, 1.31; 95% CI, 0.96 – 1.78), although this finding was nonsignificant by a narrow margin (P = .09). The risk for AD was 53% higher (HR, 1.53; 95% CI, 1.05 – 2.23).

The study found similarly marginal increased risks for dementia with exposure to organochlorines (HR, 1.33; 95% CI, 0.96 – 1.85) and for AD (HR, 1.49; 95% CI, 0.99 – 2.24).

Dr. Hayden added that no recommendations about avoiding use of pesticides can be made based on this observational study.

"Conclusions about causality cannot be drawn," she said. "The effect was relatively small and was associated with occupational exposures." However, she added, "We would certainly recommend that any individuals using pesticides follow all stated safety instructions and precautions whether they are used in an occupational setting or otherwise."

Reduced Acetylcholine

Invited to comment on this study by Medscape Neurology, Ronald Peterson, MD, PhD, chair of the Alzheimers Association Medical and Scientific Advisory Council and professor of neurology and Cora Kanow Professor of Alzheimers Disease Research at the Mayo Clinic in Rochester, Minnesota, lauded the study authors for their efforts.

"This is a well done study by a very accomplished group of researchers," Dr. Peterson said. "They are well trained and not an inexperienced group. They are scholars in the field."

Little research has been done on environmental causes of AD, he said. This study sheds important light on causes related to the environment.

Dr. Peterson also pointed out that organophosphate compounds, which are the most commonly used pesticides, are known to reduce acetylcholine, which is important for learning, memory, and concentration functions in the human brain.

"Acetylcholine goes down in AD. The pharmacokinetic action of 3 of the 4 drugs on the market for Alzheimers disease counteract that and increase the amount of acetylcholine, so it is curious that the action of these pesticide chemicals works against that of acetylcholine," he added. "This may be a clue as to why they are associated with an increased risk of the disease."

The study was supported by the National Institutes of Health/National Institute on Aging. Dr. Hayden disclosed that she serves as senior editor of Alzheimers & Dementia and that she receives research support from the National Institutes of Health. Dr. Peterson has disclosed no relevant financial relationships.