Neurology: Scientists have found that obese women have a significantly lower risk of Parkinson's disease!

*For medical professionals only

As the saying goes: one fat and a hundred sick people
.

Obesity not only leads to body anxiety, but is also associated with the occurrence and development of various health problems such as type 2 diabetes and cardiovascular disease [1-2].

However, some studies have found that obese patients may have better clinical outcomes in the study of chronic heart failure, cancer and other diseases [3-4], an unexpected association also known as the "obesity paradox", and the role of obesity in the disease does not seem to be so black
and white.

Interestingly, obesity may even be significantly associated with a reduced risk of developing certain diseases, as evidenced by Parkinson's disease studies
.

Recently, Alexis Elbaz's research team from the University of Paris Saclay published an important research result in the journal Neurology [5].

The researchers analyzed a cohort of 96,702 women and found that obese participants (BMI ≥ 30kg/㎡) were associated with a 24% lower risk of Parkinson's disease than participants with a normal BMI, and even with a longer diagnostic lag time to rule out the possibility of causal inversion, the association between obesity and Parkinson's disease risk did not change
.

In addition, their analysis of waist circumference and waist circumference/height ratio reached similar conclusions, with a trajectory analysis of BMI suggesting that the proportion of obesity in Parkinson's disease patients was significantly lower than that of control people 29 years before diagnosis, and further decreased
5-10 years before diagnosis.

This study uses long-term follow-up cohort and a variety of repeated measured weight indexes to overcome the shortcomings in previous studies and confirm the interesting inverse association between body mass index and Parkinson's disease risk, which provides ideas and references
for future research design and development.

Article title picture

The relationship between the risk of Parkinson's disease and body mass index has always been confusing
.
Different meta-analyses have also reached very different conclusions
.
Some studies have suggested that body mass index is not associated with the risk of developing Parkinson's disease [6], but the results of other studies suggest that there is an association between low body weight and an increased risk of developing Parkinson's disease [7].

Differences in different follow-up times, number of measurements, and indicators may contribute to these heterogeneities
.

Consider that Parkinson's disease may have a long prodromal phase [8], and the prodromal symptoms associated with Parkinson's disease can affect
diet, physical activity, etc.
Studies have suggested that patients with Parkinson's disease may experience weight loss 2 to 7 years before diagnosis [9-10].

How to overcome the causal inversion of the association between body weight and the risk of Parkinson's disease, and how to increase the convincing conclusion with more detailed weight measurement indicators and multiple repeated measurements, became the research topic
that Elbaz's team wanted to solve.
To do this, they analyzed
a large long-term cohort.

Elbaz's team selected data from 96,702 women who completed follow-up between 1990 and 2018 in the E3N cohort in France, and the participants' height, weight, lifestyle, and medication history were collected at baseline and at 2-3 years of follow-up in the later 2-3 years, while medication and medical visits were updated every three months with reference to the health insurance database, and participants' deaths and causes of death were collected
during the follow-up period.

The diagnosis and diagnosis time of Parkinson's disease are based on medical records, self-reported questionnaires, anti-Parkinson's drug use and cause of death, and are evaluated by neurologists and reliable algorithms to exclude drug-induced Parkinson's disease
.
The incidence of Parkinson's disease in the final E3N cohort is also similar to that revealed by the Global Burden of Disease Study [11].

Considering that the prodromal period before the onset of Parkinson's disease is difficult to identify, the study used follow-up data from the fifth year after baseline data collection to assess the risk of Parkinson's disease, and patients with Parkinson's disease who developed within five years were excluded to rule out the possibility
of causal inversion.
In sensitivity analysis, researchers also used diagnostic lag times of 10 years and 20 years
.
The researchers also selected 1196 patients with Parkinson's disease and 23876 control populations in the E3N cohort to design a nested case-control study to analyze the trajectory
of body mass index.

Overall, a total of 1164 participants were diagnosed with Parkinson's disease
during the 24-year follow-up period.
Participants in the obese group were associated with a 24% reduction in the incidence of Parkinson's disease compared with the normal BMI group (hazard ratio: 0.
76, 95% CI: 0.
59 to 0.
98), and the association between obesity and a lower risk of Parkinson's disease did not change
after setting the diagnostic lag time to 10 or 20 years, or correcting for dietary and dyslipidemia, diabetes and other mediating factors.

Association analysis between body mass index over time and risk of developing Parkinson's disease

In an analysis with a diagnostic lag time set to 10 years, a larger waist circumference, waist circumference to height ratio was significantly associated
with a lower risk of Parkinson's disease.

In the trajectory analysis of body mass index, the frequency of obesity increased steadily in the control group, while the data in the Parkinson's disease patient group began to decline
in the decade before diagnosis.
During the 29 years of follow-up, obesity was significantly lower
in the Parkinson's disease group.

Association analysis between body size indicators over time and the risk of developing Parkinson's disease

Overall, the study used repeated measurements of large samples and long-term follow-up to use a variety of well-established statistical methods to provide a credible analysis
of the association between body mass index over time and the risk of Parkinson's disease.
After trying to rule out the possible effects of causal inversion, obesity was significantly associated with a lower incidence of Parkinson's disease, and weight began to change
in the Parkinson's patient group in the decade before the onset of illness.
The results of this study also suggest that the association between metabolism and the incidence of Parkinson's disease is worth further exploring
.

Interestingly, the Mendelian randomization study, which predominates the interference of confounding factors and analyzes causality, suggests an inverse association between BMI/obesity-related features and Parkinson's disease risk [12-14], which is similar
to the conclusions of this study.
The researchers analyzed that the association between obesity and low Parkinson's disease risk may be related to blood glucose metabolism/insulin signaling pathways or microbiota, but the details are still to be clarified
.
The positive association between obesity and dementia progression [15] also suggests the complexity
of the mechanisms behind different types of neurodegenerative diseases.

However, there are some shortcomings in this study, such as: the cohort population is mostly well-educated teachers, which may not be representative of the entire population; The limited proportion of obese people also limits the further subdivision of population subgroups; Studies included only women, and whether the conclusions apply to men remains to be explored; The measurement of self-reported BMI may also have some bias; The high correlation and collinearity between body mass index and waist circumference and waist circumference height ratio also limit the analysis
of single indicators and combined effects.
But overall, the flaws are not hidden
.

The human body is a sophisticated and complex whole, and the influencing factors behind different diseases are very different, and similar discoveries can also stimulate human curiosity and continue to explore the complex correlation between diseases and physiological and pathological processes
.
Figuring out the culprits of various diseases under the appearance of body size can also better justify obesity
.

References

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