Relationship Between Disease Risk, Protective Factors Studied

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A previously identified risk factor for the development of Parkinson’s disease  — indigestion — and two protective factors (exercise and caffeine consumption) are associated with the severity of symptoms after disease onset, a study has found.

Caffeine use also was tied to a later age of disease onset.

“Our novel findings suggest that risk and protective factors of [Parkinson’s] development are associated with clinical features of [Parkinson’s] patients, including age at onset and motor and non-motor symptom severity,” the researchers wrote.

The team added that the findings, “may represent the first step in developing new preventive and therapeutic approaches able to delay disease onset or mitigate the extent of clinical manifestations.”

The study, Relationship between risk and protective factors and clinical features of Parkinson’s disease,” was published in Parkinsonism and Related Disorders.

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While the exact cause of Parkinson’s is not completely understood, it is thought that both genetic and environmental risk factors may contribute to its development.

Previously, a research team in Italy compared clinical features of 694 people with Parkinson’s to 640 healthy people and found that a family history of the disease, indigestion (dyspepsia), and exposure to toxins or anesthesia were the strongest predictors of Parkinson’s development.

They also found that coffee consumption, smoking, and physical activity were the strongest protective factors against the disease’s onset.

The research team now explored the relationship between these risk or protective factors and the clinical features of Parkinson’s among the 694 Parkinson’s patients. Their mean age at motor symptom onset was 60.7 years, and the mean disease duration among the group was 7.2 years.

Results showed that coffee consumption prior to the emergence of symptoms was associated with a later age at disease onset. More specifically, the analysis showed that coffee drinkers developed Parkinson’s symptoms about six months later than those who don’t drink coffee.

Coffee-drinkers also developed more mild motor symptoms, as measured by the International Parkinson and Movement Disorder Society5 sponsored Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III, which is consistent with previous observations regarding the protective effects of caffeine on Parkinson’s development and progression, the team noted.

According to the researchers, this protective effect may be mediated by caffeine’s ability to protect nerve cells and increase brain levels of dopamine, the signaling chemical that is deficient in Parkinson’s.

Non-motor symptoms were measured with the Non-Motor Symptoms Scale (NMSS) for Parkinson’s, which is a composite score encompassing symptoms like gastrointestinal side effects, sleep disturbances, mood, or attentional problems.

Patients who were physically active before symptom onset were more likely to have milder non-motor symptoms. Exercise is thought to lower Parkinson’s risk by exerting neuroprotective effects and modulating the function of several brain chemicals, including dopamine. Such modulations also might modify Parkinson’s non-motor symptoms, the team suggested.

In contrast, more severe non-motor symptoms were experienced by those who had a history of indigestion, a broad term referring to an upset stomach, or symptoms like abdominal pain, nausea, or a burning feeling in the abdomen. This relationship remained significant even when removing gastrointestinal symptoms from the analysis, suggesting that indigestion broadly influences non-motor Parkinson’s symptoms. It has been proposed that inflammation in the gut may contribute to Parkinson’s disease, which the researchers hypothesized might underlie this link.

The other previously identified risk or protective factors — smoking and exposure to toxins or anesthesia — were not associated with any Parkinson’s clinical features, suggesting that while they may influence disease onset, they are not involved in its progression.

No relationship was observed between any of the risk or protective factors and patients’ prescribed dose of levodopa, which is a standard Parkinson’s therapy aimed at increasing brain dopamine levels.

Overall, the results suggest that “physical activity and caffeine seem to be promising candidates for future preventive and therapeutic approaches in [Parkinson’s] patients,” the researchers wrote.

“Although we investigated exposure to risk and protective factors in the period that preceded [Parkinson’s] development, it is possible that the same factors may still be present after diagnosis and may influence disease progression,” they added.

“Therefore, the next step should be to design longitudinal studies assessing the neuroprotective power of caffeine and physical activity on prodromal [presymptomatic], early, and moderate/advanced phases of [Parkinson’s].”

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