Parkinson's Disease on the Rise?

A new study shows that the incidence of parkinsonism and Parkinson's disease (PD) increased between 1976 and 2005, more than doubling in older men during this period.

The authors believe the rise is not just a result of greater awareness or changes in medical practice, but represents a real trend.

They speculate, for example, that it could be associated with dramatic changes in smoking behavior during the second half of the 20th century (smoking has been inversely associated with PD risk) or with other lifestyle or environmental changes, said study author Walter A. Rocca, MD, from the Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.

However, it is also possible that the trend could be "spurious" and needs to be confirmed in other populations. If confirmed, however, it could have major implications for public health and for our understanding of the causes of PD, said Dr Rocca.

The study was published online June 20 in JAMA Neurology.

Researchers at the Mayo Clinic used the 50-year-old records-linkage system of the Rochester Epidemiological Project, which allowed them to access complete electronic medical records of residents of Olmsted County, Minnesota, over the course of several decades.

They defined parkinsonism as the presence of at least two of four cardinal signs: rest tremor, bradykinesia, rigidity, and impaired postural reflexes. Parkinsonism can include diseases such as Lewy body dementia and progressive supranuclear palsy.

PD was defined as parkinsonism with all three of the following features: no other cause, no documentation of unresponsiveness to levodopa, and no prominent or early (less than a year from onset) signs of more extensive nervous system involvement.

Researchers identified 906 people with parkinsonism with onset between January 1, 1976, and December 31, 2005. Age-adjusted incidence rates of parkinsonism were stable for women during this 30-year time frame, but increased for men from 38.8 to 56.0 cases per 100,000 person-years.

The analysis showed a significant increase in incidence rates for men (relative risk [RR], 1.17 per decade; 95% confidence interval [CI], 1.03 - 1.33; P = .01), but not for women.

The increase in incidence rates was greater for men 70 years or older (RR, 1.24 per decade; 95% CI, 1.07 - 1.44; P = .005) than in younger men.

PD Rates

There were 464 patients with PD identified as having onset during the study period. The age-adjusted incidence rate of PD increased in men during this period, going from 18.2 to 30.5 per 100,000 person years.

Here, too, there was a significant increase in incidence rates for men (RR, 1.24 per decade; 95% CI, 1.08 - 1.43; P = .003), but not for women.

Again, the increase was greater for men aged 70 years or older (RR, 1.35 per decade; 95% CI, 1.10 - 1.65; P = .004) than for younger men.

However, the age by calendar year interaction in men was not significant. Women aged 70 years or older also experienced an increase in the incidence of rate of PD, but the trend was not significant.

Interestingly, the researchers found a significantly higher incidence of PD in men born between 1915 and 1924. It is possible that an intrauterine infection or another intrauterine event such as inadequate diet or lack of some nutrient played a role in causing this trend, said Dr Rocca. "But we need to further explore these hypotheses."

The authors stress that the findings should be interpreted with caution, as the trends may be "an artefact" caused by increased awareness of signs and symptoms of PD. However, the fact that the trends were more evident in men than women may support a genuine trend, they said.

They do not believe a change in coding practices contributed greatly to the increase.

Smoking Theory

The smoking theory may, however, hold some weight. Back in 2008, other researchers found that smokers have a 74% reduced risk for PD because of some protective constituents of tobacco.

In 1965, 51.9% of men and 33.9% of women smoked, but by 2009, these rates had dropped to 23.5% and 17.9%, respectively.

However, aside from smoking and infections, other environmental, behavioral, or lifestyle factors may help explain changing PD rates. For example, said Dr Rocca, the last century has witnessed major changes in physical activity, diet, and other daily life activities, as well as in the use of herbicides and pesticides in agriculture.

"If the trends are related to chemical substances used in agriculture, men may have been more directly exposed than women; for example, they did the spraying in the fields," he said.

PD affects more men than women, with a ratio of about 3 to 2.

In an accompanying editorial, Honglei Chen, MD, PhD, from the Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, said data on reliable estimates of PD prevalence and incidence rates over time "are urgently needed to project future disease burden, allocate medical resources, and assist with understanding disease etiology."

Although other studies have reported a stable or slightly decreased PD incidence over the years, they examined short-term changes, "which cannot readily inform long-term trends," said Dr Chen. Also, these studies mostly identified patients with PD using "algorithmic searches" of databases without additional diagnostic validation.

Medscape Medical News also invited James Beck, PhD, vice president, scientific affairs, Parkinson's Disease Foundation, to comment. These types of studies, said Dr Beck, "are long overdue," especially as the population ages.

"We know so little about who has PD in the US and the implications this has for society and for research and for pharma. The more information we have empowers the community and allows us to make the decisions we need to make" in terms of caring for patients and research investments, he said.

A "unique" aspect of the study is the use "an incredibly rich dataset," that "you can view as the Cadillac of electronic medical records," said Dr Beck. "Invariably, everybody with PD in that community gets seen by movement disorder neurologist."

On top of that, he added, the authors were able to adjudicate whether the diagnoses were accurate.

Although the current study sheds light on incidence rates, the Parkinson's Disease Foundation has launched the Parkinson's Disease Foundation's Parkinson's Prevalence Project to learn more about who actually has PD. It is working with several groups across the United States, including the authors of this current study, to come up with a revised estimate of the number of Americans with PD.

Although the exact revised estimate likely will not be available until later this year, "preliminary estimates are that it is closer to 1 million while the government cites 650,000," a number that has been extrapolated from a study in the late 1970s, said Dr Beck.

Medscape Medical News also spoke to Serge Przedborski, MD, PhD, president and founding member, World Parkinson Coalition, who found the study "interesting," and said that "it would be a mistake to ignore it," since it "raises an important point."

However, Dr Przedborski does not think "we should make a big deal" of the study because of "intrinsic limitations."

One of the problems, he said is relying on data from the 1970s when awareness of PD was quite different.

"The reason behind the change in those numbers may not be telling us anything except perhaps that the way we diagnose people has tremendously changed, and the way people seek medical opinion has completely changed," he said.

For example, in the 1970s, many people with parkinsonian features "stayed home, and the last thing they wanted was to go and display their symptoms, even to their physician or the rest of the family."

Back then, physicians considered PD as something they could not do very much about and as less problematic than other disorders patients might have been grappling with, such as diabetes or heart disease, he noted.

Dr Przedborski took issue with the smoking theory the authors raised, but left unanswered questions about the connection between this habit and lower PD rates.

For example, he said, the study found that the increases in the PD incidence rate are most pronounced in older men. "I'm not sure those are the ones who really reflect most of the change in smoking habits," said Dr Przedborski. "If anything, I would have thought that it's more the younger ones who smoke less."

The authors not only do not characterize smoking in the context of aging, but also in the context of sex. The PD incidence rate among women has not changed, but along with men, their smoking rates have also plummeted over the years.

"Are they saying that men have changed their smoking habits more than women? They never come back to that."

Dr Rocca told Medscape Medical News that the increase and decrease in smoking during the last century were less extreme in women that in men.

Dr Przedborski also questioned the sex differences in PD incidence rates in the various age categories. In those aged 60 to 69 years, the difference is not that wide, but "all of a sudden, you see a big difference at 70 years and beyond," he said. "Is this because men are dying of heart attack and so are more likely to have PD? I don't know."

The study was carried out in one county in the United States, which could reflect "a cluster effect," he added.

"Before we can make any conclusions about those numbers and what they mean, we have to make sure that, as provocative as they are, they would be reproducible in other places where they have access to a reasonably homogenous population and confirm those numbers, because otherwise it could be a fluke," he concluded.

The study was supported by the National Institute on Aging of the National Institutes of Health and by the Mayo Foundation for Medical Education and Research. Dr Rocca and Dr Chen have disclosed no relevant financial relationships.


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SOURCE: Medscape. June 23, 2016. Parkinson's Disease on the Rise?

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