Adherence to dietary patterns that emphasize vegetables, fruits, nuts, and grains, such as in the Mediterranean diet, is inversely associated with prodromal features of Parkinson’s disease (PD), including constipation, excessive daytime sleepiness, and symptoms of depression, new research suggests.
These results, from a cohort study of more than 47,000 participants, are consistent with findings from previous research, the investigators note.
Although the current study suggests that adherence to a healthy diet may reduce occurrence of nonmotor symptoms that precede the diagnosis of PD, prospective research is now needed to determine whether adherence can delay or prevent the onset of the disease itself in patients with prodromal symptoms, they add.
A growing body of evidence suggests that the gut and enteric nervous system may be involved in the pathogenesis of PD, noted lead author Samantha A. Molsberry, PhD, a postdoctoral research fellow at Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Following a healthy dietary pattern may influence risk for PD or prodromal PD features “by protecting against α-synuclein aggregation in the gut or by otherwise promoting gut health in a manner protective against degeneration in the enteric nervous system or CNS,” she told Medscape Medical News.
Healthy diets include foods that are high in antioxidant and anti-inflammatory compounds. Therefore, diet pattern may “reduce risk of Parkinson’s disease or prodromal Parkinson’s disease features by preventing oxidative stress and neuroinflammation,” Molsberry added.
The findings were published online August 19 in Neurology.
First Longitudinal Study
A prodromal period of 10 years or longer precedes the onset of PD. During this time, patients may have various nonmotor symptoms that, although they are nonspecific individually, are strongly associated with PD when they occur together. Various foods and dietary patterns have been associated with the risk of developing PD. No previous longitudinal studies had examined the relationship between diet and prodromal features of PD.
Results from the previous Hellenic Longitudinal Investigation of Aging and Diet showed an inverse association between adherence to the Mediterranean diet and risk of prodromal PD.
However, “our study differs from their investigation in that we were able to use prospectively measured diet information that has been regularly collected in our cohorts since the 1980s, which minimizes the chance of reverse causation explaining our results,” Molsberry noted.
Additionally, the investigators analyzed a second diet pattern: the Alternative Healthy Eating Index.
“While we found similar results as Maraki et al. with respect to the Mediterranean diet pattern, we also found similarly strong associations between the Alternative Healthy Eating Index and prodromal features of Parkinson’s disease,” said Molsberry.
Focus on Early Symptoms
The investigators examined data from the Nurse’s Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). The NHS included 121,700 female nurses who were between ages 30 and 55 years at enrollment in 1976. The HPFS included 51,529 male health professionals between ages 40 and 75 years at enrollment in 1986.
Participants in both studies responded to biennial questionnaires about lifestyle practices, occupational and other exposures, and medical history.
The current analyses included all participants under age 85 years without PD who responded to the baseline food frequency questionnaire and to questions about probable REM sleep behavior disorder (RBD) and constipation on the 2012 questionnaire. A subset of eligible participants underwent secondary screening that included olfactory testing and a premotor PD questionnaire.
The researchers focused on the prodromal symptoms of constipation, probable RBD, hyposmia (partial loss of smell), excessive daytime sleepiness, impaired color vision, depressive symptoms, and body pain. The 2012 questionnaire was used to assess constipation and probable RBD. The other symptoms were assessed using common tests, such as the Brief Smell Identification Test and the Epworth Sleepiness Scale.
Participants’ responses to the food frequency questionnaires were used to evaluate their adherence to the alternate Mediterranean diet (aMED, the primary analysis) and the Alternative Healthy Eating Index (AHEI, the secondary analysis). Adherence to aMED was gauged according to participants’ consumption of vegetables, excluding potatoes; fruits; nuts; whole grains; legumes; fish; monounsaturated and saturated fat; red and processed meats; and alcohol.
Adherence to AHEI was based on consumption of vegetables, fruits, whole grains, sugar-sweetened beverages and fruit juice, nuts and legumes, red and processed meat, trans fat, long-chain (n-3) fats, polyunsaturated fatty acids, sodium, and alcohol.
The analyses included 29,899 NHS participants and 17,770 HPFS participants. In both cohorts, participants with higher adherence to the aMED diet were older, were less likely to be current smokers, were more physically active, had a lower BMI, and consumed less caffeine and more total energy than participants with lower aMED adherence.
Among participants who completed screening for prodromal features, 1729 in the NHS and 1155 in the HPFS had no features. In addition, 1966 NHS participants and 950 HPFS participants had three or more prodromal features.
At baseline and over the long term, adherence to a Mediterranean-style diet was inversely associated with combinations of prodromal symptoms. When participants in the highest and lowest quintiles of aMED adherence were compared, the multivariable adjusted odds ratio (OR) for having three or more prodromal features compared with having none was 0.82 at baseline and 0.67 for long-term diet.
The results for AHEI adherence were stronger. Comparing the highest and lowest quintiles of adherence, the adjusted OR for having three or more prodromal features compared with having none was 0.72 at baseline and 0.66 for long-term diet.
Similar associations were found between adherence to aMED and AHEI and the ORs of having two prodromal symptoms vs having none.
The same associations held when the investigators examined the OR of having one prodromal symptom vs having none. As the number of symptoms decreased, however, the strength of the association decreased.
In further analyses, increased aMED adherence at baseline was inversely associated with constipation; and increased long-term aMED adherence was inversely associated with constipation, excessive daytime sleepiness, and depressive symptoms. Results were similar for adherence to AHEI.
Molsberry noted that neurologists may want to recommend that patients eat healthy diets rich in fruits, vegetables, nuts, and legumes. Intake of red meat and processed foods should be low to moderate, she added.
The investigators are continuing to follow the cohort over time to observe how prodromal PD features evolve and to determine which participants go on to develop clinically-manifest PD, Molsberry reported.
“This will allow us to further investigate whether certain behaviors and lifestyle choices, such as adherence to a healthy diet, are associated with whether an individual with prodromal features of Parkinson’s disease goes on to develop Parkinson’s disease and how quickly he or she does so,” she said.
Impressive, but Several Limitations
Commenting for Medscape Medical News, Brit Mollenhauer, MD, professor of neurology at the University Medical Center Goettingen and head of clinical research at Movement Disorder Paracelsus-Elena-Klinik in Kassel, Germany, noted that a significant study weakness is that not all patients with prodromal symptoms will develop PD.
The cohorts were also probably biased toward the inclusion of more educated individuals, said Mollenhauer, who was not involved with the research.
In addition, some prodromal symptoms such as RBD “cannot reliably be diagnosed with one question alone” and patients with restless legs syndrome can receive an incorrect diagnosis of RBD, which can be triggered by sleep apnea or medication.
The analysis also did not account for comorbidities, polypharmacy, or other factors such as exercise, Mollenhauer said.
“But I am impressed by the numbers of subjects and the detailed information on nutrition and on some prodromal symptoms” in the current research, such as the smell test, she noted. “There still needs to be a lot of basic studies showing the direct relationship of nutrition and Parkinson’s disease, but with microbiome analyses, for example, this [task] is under way.”
If a patient who presents for early diagnosis of PD is obese, and thus may have diabetes and other vascular risk factors, Mollenhauer recommends exercise and dieting, advising that PD symptoms will not progress as much with this approach.
“But the problem is often that neurologists see the people when they already shake, so maybe other doctors should be involved and there should be much more invested in prevention and awareness of age-related disorders,” Mollenhauer said.
The study was funded by the US Department of Defense. The NHS and HPFS cohorts are funded by the National Institutes of Health. Molsberry and Mollenhauer have disclosed no relevant financial relationships.
Neurology. Published online August 19, 2020. Abstract