Environmental pesticide exposure and Alzheimer's disease in southern Spain: A cross-sectional study, 2024, Ruiz-González et al

[forestglip]

Environmental pesticide exposure and Alzheimer's disease in southern Spain: A cross-sectional study

Cristofer Ruiz-González, Pablo Román, Lola Rueda-Ruzafa, Diana Cardona, Mar Requena, Raquel Alarcón

Abstract
The intensive cultivation under plastic in southern Spain has made the agricultural model highly productive. Although strict regulations on pesticide usage exist, exposure to pesticides in the environment has been associated with an increased appearance of neurodegenerative diseases including Alzheimer's disease (AD).

A cross-sectional study was performed to examine the prevalence and risk of AD related to pesticide exposure in Andalusia (Spain). We utilized the Odds Ratio statistical test to compare the prevalence rate of AD in the exposed and unexposed areas. 40,044 cases were collected from computerized hospital records between 2000 and 2021.

Districts with higher pesticide use showed significantly higher prevalence rates and increased risk of developing AD, compared to those with lower pesticide use.

These findings provide further evidence supporting an increased risk of AD following environmental exposure to pesticides at the level of the general population.

Link | PDF (Psychiatry Research) [Open Access]

 

[forestglip]

They divided Andalusia into two areas based on pesticide use.

The selected areas for the study encompassed the healthcare districts of Andalusia, located in southern Spain, and were divided into areas with high and low pesticide usage, based on the percentage of greenhouse hectares. The high-usage areas accounted for 93.2 % of the total greenhouse surface area in Andalusia and consumed 14,002 tons of pesticides, representing 91.4 % of the total. In contrast, low-usage areas represented only 6.8 % of the greenhouse surface area and consumed 1306 tons, equivalent to 8.6 % of the total.

Case/control criteria

The cases were identified through the Basic Minimum Data Set (BMDS), a computerized registry maintained by the Public Health Service of Andalusia. Criteria for excluding cases included being under 60 years old and not residing in the designated study areas (Prince et al., 2015). The accuracy of the BMDS data is determined by the quality of discharge reports and the completeness of hospital discharge coding.

During the study period, the diagnosis of AD was determined based on the ninth and tenth revisions of the International Classification of Diseases (ICD-9 and ICD-10) as defined by the World Health Organization. The ICD-9 code used for AD was 331.0, while the ICD-10 codes used were G30.0 for early onset AD, G30.1 for late onset AD, G30.8 for other types of AD and G30.9 for unspecified AD.
The comparative group used consisted of patients from the same geographical areas, without mental or cognitive pathology, identified through the BMDS.

No differences in ages.

The mean age of individuals diagnosed with AD in areas of high pesticide use was 81.03 (6.76) years, and in areas of low pesticide use, the mean age was 81.10 (6.29) years. No statistically significant differences were observed (Table 1). The mean age of the control population in areas of high pesticide use was very similar to that in areas of low pesticide use (81.45 (10.47) years vs 81.63 (10.79) years; p > 0.05).

After adjusting for age and sex, they found an odds ratio of 1.64 (1.41-1.89) for having Alzheimer's in the high pesticide areas.

Trend of prevalence over time in the two areas:


Past research on chemical exposure and disease

In line with our discovery, a positive correlation exists between pesticide exposure and neurodegenerative ailments like AD, Parkinson's disease, and multiple sclerosis (Baldi et al., 2003; Parrón et al., 2011; Yan et al., 2016). Nevertheless, certain studies have not established a significant link between pesticide exposure and the likelihood of developing AD (Gauthier et al., 2001; Steenland et al., 2013). Despite these findings, serum levels of specific pesticides or their byproducts have shown a marked increase in AD patients compared to control subjects (Kiani et al., 2022; Richardson et al., 2014). Additionally, numerous studies have suggested that organophosphate pesticides can modify amyloid beta (Aβ) protein levels or promote neuroinflammation (Laksmidewi et al., 2020; Salazar et al., 2011; Winstone et al., 2022).

These findings are consistent with numerous studies indicating that environmental pollutants like heavy metals or acidic substances present in both air and soil might be linked to dementia (Yan et al., 2022; Yang et al., 2018). Prolonged exposure to airborne gaseous pollutants or fine particulate matter heightens the risk of cognitive decline and neurodegenerative ailments (Peters et al., 2019; Tan et al., 2022; Yan et al., 2022). Additionally, elevated levels of heavy metals, such as arsenic found in urine, might be linked to a higher risk of AD (Yang et al., 2018). Furthermore, exposure to heavy metals has been associated with the underlying mechanisms of AD, influencing the aggregation of Aβ protein or causing disturbances in the levels of tau hyperphosphorylation (Fujimura et al., 2009; Gu et al., 2011). Consistent with this, exposure to organochlorines, organophosphates, or bipyridyls has demonstrated the induction of neuronal damage associated with AD in experimental assays (Chen et al., 2012; Richardson et al., 2014; Salazar et al., 2011).

There is discussion about how they found higher prevalence of Alzheimer's in females, including possible mechanisms.

Notably, stratification of the data by sex showed that females living in high-exposure districts had a higher risk of AD than males did. Similarly to our results, an ecological study revealed an elevated risk for women exposed to pesticides compared to men (Parrón et al., 2011). [...] Certain pesticides have been associated with disruptions in the endocrine system in both sexes, potentially affecting the synthesis, secretion, metabolism and transport of sex hormones such as estrogen and androgens (Bretveld et al., 2006; Lemaire et al., 2004). Others may activate or inhibit receptors, and some may affect gene expression through epigenetic modifications, such as DNA methylation or histone modifications (Hoang et al., 2021; Lemaire et al., 2006; Maness et al., 1998; Song et al., 2010).

Evidence gathered from a variety of research studies indicates a potential link between disruptions in sex hormone levels and an increased risk of cognitive decline in both men and women. [...] Along these lines, studies have proposed that postmenopausal women who undergo estrogen hormone replacement therapy may experience a reduced risk of dementia compared to those who do not receive such treatment (Ali et al., 2023; Jamshed et al., 2014). Similarly, there is evidence indicating a potential association between androgen deprivation therapy for prostate cancer in older men and an increased risk of cognitive decline and dementia (Kim et al., 2022).

In terms of limitations - specifically socioeconomic confounders - while the proportion of people working in the primary sector (agriculture and livestock, forestry and fishing) was significantly higher in the high pesticide areas, and proportion working in secondary sector (manufacturing industry and construction) was lower, the average disposable personal income in the two areas was not significantly different.

 

[forestglip]

I'd like to see if the association holds if they split it into further than two areas, stratified by exposure level.

Also, it'd be interesting to do this with all diseases there is data for in the same two areas and see if the diseases most and least correlated to pesticide exposure are consistent with prior research. I wonder how hard that data is to get.