Participants for whom religion was “not at all important” in their lives had a tenfold risk of developing Parkinson's disease (vs. very important); plus there was a dose–response relationship between decreasing religiosity & more PD risk

Religiosity and Risk of Parkinson’s Disease in England and the USA. Abidemi I. Otaiku. Journal of Religion and Health, Jun 28 2022. https://rd.springer.com/article/10.1007/s10943-022-01603-8

Abstract: Parkinson’s disease (PD) is associated with low religiosity cross-sectionally. Whether low religiosity might be associated with an increased risk for developing PD is unknown. This study investigated whether low religiosity in adulthood is associated with increased risk for developing PD. A population-based prospective cohort study was conducted. Participants from the English Longitudinal Study of Aging and the Midlife in the United States study who were free from PD at baseline (2004–2011) and completed questionnaires on self-reported religiosity, were included in a pooled analysis. Incident PD was based on self-report. Multivariable logistic regression was used to estimate odds ratios (OR) for developing PD according to baseline religiosity, with adjustment for sociodemographic characteristics, health and lifestyle factors and engagement in religious practices. Among 9,796 participants in the pooled dataset, 74 (0.8%) cases of incident PD were identified during a median follow-up of 8.1 years. In the fully adjusted model, compared with participants who considered religion very important in their lives at baseline, it was found that participants who considered religion “not at all important” in their lives had a tenfold risk of developing PD during follow-up (OR, 9.99; 95% CI 3.28–30.36). Moreover, there was a dose–response relationship between decreasing religiosity and increasing PD risk (P < 0.001 for trend). These associations were similar when adjusting for religious upbringing and when cases occurring within the first two years of follow-up were excluded from the analysis. The association was somewhat attenuated when religious practices were removed from the model as covariates, though it remained statistically significant (OR for “not at all important” vs. “very important”, 2.26; 95% CI 1.03–4.95) (P < 0.029 for trend). This longitudinal study provides evidence for the first time that low religiosity in adulthood may be a strong risk factor for developing PD.

Discussion

Using prospective data from two population-based cohort studies in England and the USA, the current study shows for the first time that low religiosity in adulthood may be associated with an increased risk for developing PD, accounting for a wide range of potential confounders.

The findings of this longitudinal study are consistent with previous cross-sectional studies, which showed a robust association between PD and low religiosity (Boussac et al., 2021; Butler et al., 2010; Butler et al., 2011; Giaquinto et al., 2011; Kéri & Kelemen, 2016; McNamara et al., 2006; Pham et al., 2021), case-reports showing improvement of parkinsonism after intense religious experiences (Moreno & de Yebenes, 2009) and theoretical work, that has offered biologically plausible mechanisms by which religiosity could confer neuroprotection in PD (Yulug et al., 2015). The results are also in keeping with a recent neuroimaging study (Ferguson et al., 2022), which showed that brain lesions causing parkinsonism, intersect brain regions associated with religiosity.

It is noteworthy that participants who considered spirituality very important in their lives but not religion, had a higher risk for developing PD than participants who considered religion very important, and also participants who considered neither spirituality nor religion very important. This finding is consistent with an earlier study, which showed that individuals with PD, though less likely to have religious beliefs than matched controls, are on the other hand more likely than controls to have spiritual beliefs (Giaquinto et al., 2011). As such, this study corroborates previous research which suggests that individuals who have a spiritual understanding of life in the absence of a religious framework, may be more vulnerable to developing neuropsychiatric disorders (King et al., 2013; Vitorino et al., 2018).

These results are also in agreement with previous studies, which found higher religiosity to be associated with lower risk of developing a wide range of physical (Ahrenfeldt et al., 2017, 2019; Li et al., 2016), mental (Edlund et al., 2010; Miller et al., 2012; Opsahl et al., 2019) and cognitive disorders (Lin et al., 2015). However, the magnitude of the association found in this study is considerably higher than for any physical health condition previously reported, and therefore requires explanation. A recent study identified that individuals with high self-reported intrinsic religiosity may have significantly higher levels of brain-derived neurotrophic factor (BDNF) than individuals with low self-reported intrinsic religiosity (Mosqueiro et al., 2019). Given that BDNF has been shown to enhance the survival of dopaminergic neurons in animal models of PD (Palasz et al., 2020) and BDNF levels are significantly reduced in patients diagnosed with PD (Jiang et al., 2019), it is plausible that differences in BDNF levels among healthy adults with different levels of religiosity, could partially explain the dose–response relationship with PD risk observed in this study. In addition, there is accumulating evidence that dopaminergic pathways play a central role in mediating religious experience (Previc, 2006; van Elk & Aleman., 2017). A recent SPECT study found significant changes in dopamine transporter binding in the basal ganglia after attendance at a one-week Christian retreat (Newberg et al., 2018). Earlier studies showed increased dopamine release in the ventral striatum during certain forms of meditation (Kjaer, et al., 2002) and increased blood flow to the caudate nucleus during silent religious prayer (Schjødt et al., 2008). These studies suggest that habitual engagement in religious activities could modify dopamine levels in brain regions linked to PD pathology. Therefore, given strong preclinical evidence that enhancing dopamine neurotransmission with dopamine agonists confers neuroprotection in PD (Schapira & Olanow, 2003); it is plausible that individuals with higher religiosity, also have higher midbrain dopamine levels, and consequently have more protection against developing PD.

It is important to note however, that these results do not necessarily imply that religious participation should now be promoted by public health agencies as a preventative measure for PD; given that people’s religious beliefs and commitments are highly personal, and are not usually arrived at based on health concerns. Moreover, further studies are still required to confirm the exact biological mechanisms linking lower religiosity and PD.

Also, seemingly in contrast to the present findings, previous studies have repeatedly shown that clergy and religious workers—who are presumably high in religiosity—have a higher risk for developing PD compared to adults in the general population (Park et al., 2005; Schulte et al., 1996; Tanner et al., 2009). Although, this association is attenuated when the total number of years having worked in a religious occupation is adjusted for (Tanner et al., 2009). The most parsimonious explanation for this observation, would be that the increased risk for PD is confined to individuals with a religious occupation who subsequently experience a decline in religiosity. However, this suggestion is speculative and future studies will be required to confirm this hypothesis.

In addition, future studies are warranted to determine which aspects of religiosity are most associated with the risk of PD, especially given the striking change in the estimates when religious practices (particularly religious service attendance) were included as covariates in this analysis. On the surface, this would seem to imply that religious practices were harmful, i.e., participants with higher religiosity had a lower risk of developing PD despite engaging in more frequent religious practices. However, this would contradict the previously mentioned literature which seems to suggest that religious practices might be protective. Alternatively, it is possible that participants who engaged in more frequent religious practices, but considered religion relatively unimportant in their daily lives, may have exhibited low intrinsic religiosity—but high extrinsic religiosity. If so, it may be the case that having high extrinsic religiosity in the presence of low intrinsic religiosity, is an even stronger risk factor for developing PD than having consistently low religiosity (i.e., low intrinsic and extrinsic religiosity). Accordingly, adjusting for religious practices might have made the association more apparent—by isolating the effects of intrinsic religiosity on PD. Intriguingly, this theory may be in line with a recent cross-sectional study, which showed that newly diagnosed people with PD had lower intrinsic religiosity than age-and sex- matched healthy controls, despite the two groups being similar for frequency of religious practices (Kéri & Kelemen, 2016). Thus, if this theory is confirmed to be true, this might further explain why some clergy and religious workers are at higher risk of developing PD.

Strengths and Limitations

This study has several strengths, including the prospective design, long follow-up period, use of two large and well-documented population-representative cohorts, inclusion of a wide range of potential confounders, measurement of religiosity at two different time periods in two different continents and employment of a variety of sensitivity analyses. Furthermore, the participants were not selected on the basis of religiosity or PD diagnosis. Several limitations also warrant discussion. Following previous published studies (Kamel et al., 2007; Leng et al., 2018, 2020) this study relied on self-reporting to determine incident PD and therefore may have missed or misclassified some cases. Second, the small number of cases within each level of religiosity led to wide confidence intervals. It is also difficult to fully exclude the possibility of reverse causality, as low religiosity might be an early sign of undiagnosed PD, rather than a risk factor for developing PD (given that PD often has a long latency from motor symptom onset to diagnosis) (Breen et al., 2013). However, the long follow-up period coupled with the findings from the 2-year time lag analysis, suggest that low religiosity preceded the development of clinical PD. This would also be consistent with a recent longitudinal study, which showed that PD does not cause religiosity to decline (Redfern et al., 2020). Moreover, the analysis using 10-year changes in religiosity showed that becoming more religious over time reduced the subsequent risk of developing PD, which implies that low religiosity may cause PD. Previous studies have shown that PD patients with symptoms beginning on the left-side of their body, are less religious on average than PD patients whose symptoms begin on their right-side (Butler et al., 2011; Giaquinto et al., 2011). As information on PD characteristics were not available in this study, it was not possible to confirm whether individuals with low religiosity were more likely to develop left-onset PD. Finally, the findings from this study might not be generalizable to predominantly non-Christian populations (Lin et al., 2015).