A Protein-Based Study of Parkinsonism’s Incidence

How often does parkinsonism loom in a population? Scientists revisiting this question published a new analysis of the incidence of Parkinson-related diseases in the May 20 JAMA Neurology online. Walter Rocca and colleagues at the Mayo Clinic, Rochester, Minnesota, put a modern twist on their study by including rare types of parkinsonism and categorizing them by their underlying proteinopathy. “It’s important to have a current snapshot of the state of these diseases in the U.S. so that experts have an up-to-date understanding of the impact of a disease and how often it pops up in the clinic,” said first author Rodolfo Savica.

Clinicians define parkinsonism as any condition that causes some combination of resting tremor, bradykinesia, rigidity, or impaired postural reflexes. Scientists now recognize that the disorder may be caused by α-synuclein buildup—as in Parkinson’s disease (PD), other Lewy body disorders, and multiple system atrophy—or tau accumulation, as in progressive supranuclear palsy and corticobasal syndrome. Previous studies suggested an incidence rate of 10 to 18 new cases of Parkinson’s disease (PD) per year per 100,000 people (for a review, see de Lau and Breteler, 2006). However, few of these studies include rarer forms of parkinsonism, whose diagnoses are more complicated, and none divided the diseases by the toxic proteins involved.

Rocca’s group used newer diagnostic methods and more sophisticated classification of disease subtypes and pathology to mine 15 years of data from the population-based Rochester Epidemiology Project. Because the project collects detailed medical histories from all healthcare providers in Olmsted County, Minnesota, the researchers were able to capture prevalence data for the entire adult population of the county. The new study updates Rocca's previous population-based assessment of parkinsonism incidence (see Bower et al., 1999).

Using the medical histories, Savica, a movement disorders specialist, made his own clinical diagnosis for anyone who had shown some sign of parkinsonism. Of the county’s approximately 144,000 adults, he found that 542 developed parkinsonism between 1 January 1991 and 31 December 2005. Synucleinopathies were most common, afflicting 389 people, equivalent to an average of 21 incident cases per 100,000 person-years. It rose steeply after age 60—up to 205 cases per 100,000 person-years. PD was the most common type of synucleinopathy, striking 264 people, or 14 cases per 100,000 person-years. Parkinsonism with dementia, including Parkinson's disease dementia and dementia with Lewy bodies, arose 110 times, coming to 5.9 cases per 100,000 person-years, while just 15 people had developed multiple system atrophy. As in previous studies, the rates were higher for men than women. The reason for the gender difference is unknown.

Tauopathies turned up much less frequently. They made up only 4 percent of the entire disease group, with an incidence rate of 1.1 cases per 100,000 person-years. Progressive supranuclear palsy predominated, with 16 instances, followed by corticobasal degeneration, which was found in four people. Parkinsonism not driven by a known proteinopathy arose as well; 36 people developed a temporary drug-induced parkinsonism, 11 a vascular type, and 84 an unspecified variety.

Since these diagnoses were based solely on clinical observation, Savica checked them against autopsy records he had for a subset of 65 patients. Eighty percent of people with synucleinopathies and all cases with tauopathies had been correctly diagnosed. “That’s pretty good in confirming clinical diagnoses pathologically,” said Savica. It would be interesting to know if the patients for whom pathology conflicted with the clinical impression had oligomers of synuclein or tau in the brain in the absence of protein aggregates, said Sylvain Lesné, University of Minnesota, Minneapolis.

Most of these numbers confirmed the relative incidences already known. Still, Savica said he was surprised that PDD outnumbered multiple system atrophy. Drug-induced parkinsonism was down from the group’s previous report and cropped up more often in women than in men, as did corticobasal degeneration. Since the findings come from a principally Caucasian group in the U.S. Midwest, it remains to be seen if they extrapolate to a more diverse population.

The findings are consistent with existing literature, wrote Russell Swerdlow, University of Kansas Medical Center, Kansas City, to Alzforum in an e-mail (see comment below). In the next few months, Rocca's group will report the first U.S. population-based findings on the incidence of dementia with Lewy bodies. Such data exist already from an elderly cohort in southwestern France (see Perez et al., 2010). They will also report on incidence trends in the past decades.—Gwyneth Dickey Zakaib

Comments

  1. This interesting study of Olmsted County residents associates clinically evident parkinsonism with brain histology. The authors clarify several points that might prove useful to clinicians as they assign final diagnoses to applicable patients. First, most parkinsonism presentations will associate with synuclein aggregation, thereby justifying a diagnosis of Parkinson's disease. Tau aggregations typical of progressive supranuclear palsy and corticobasal syndrome are far less common.

    View all comments by Russell Swerdlow

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References

Paper Citations

  1. de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol. 2006 Jun;5(6):525-35. PubMed.
  2. Bower JH, Maraganore DM, McDonnell SK, Rocca WA. Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976-1990. Neurology. 1999 Apr 12;52(6):1214-20. PubMed.
  3. Perez F, Helmer C, Dartigues JF, Auriacombe S, Tison F. A 15-year population-based cohort study of the incidence of Parkinson's disease and dementia with Lewy bodies in an elderly French cohort. J Neurol Neurosurg Psychiatry. 2010 Jul;81(7):742-6. PubMed.

External Citations

  1. Rochester Epidemiology Project

Further Reading

Papers

  1. Perez F, Helmer C, Dartigues JF, Auriacombe S, Tison F. A 15-year population-based cohort study of the incidence of Parkinson's disease and dementia with Lewy bodies in an elderly French cohort. J Neurol Neurosurg Psychiatry. 2010 Jul;81(7):742-6. PubMed.
  2. Parnetti L, Castrioto A, Chiasserini D, Persichetti E, Tambasco N, El-Agnaf O, Calabresi P. Cerebrospinal fluid biomarkers in Parkinson disease. Nat Rev Neurol. 2013 Mar;9(3):131-40. PubMed.
  3. Horsfall L, Petersen I, Walters K, Schrag A. Time trends in incidence of Parkinson's disease diagnosis in UK primary care. J Neurol. 2013 May;260(5):1351-7. PubMed.
  4. Bauso DJ, Tartari JP, Stefani CV, Rojas JI, Giunta DH, Cristiano E. Incidence and prevalence of Parkinson's disease in Buenos Aires City, Argentina. Eur J Neurol. 2012 Aug;19(8):1108-13. PubMed.
  5. Allyson Jones C, Wayne Martin WR, Wieler M, King-Jesso P, Voaklander DC. Incidence and mortality of Parkinson's disease in older Canadians. Parkinsonism Relat Disord. 2012 May;18(4):327-31. PubMed.
  6. Willis AW, Schootman M, Kung N, Racette BA. Epidemiology and neuropsychiatric manifestations of Young Onset Parkinson's Disease in the United States. Parkinsonism Relat Disord. 2013 Feb;19(2):202-6. PubMed.
  7. Savica R, Grossardt BR, Bower JH, Ahlskog JE, Rocca WA. Risk factors for Parkinson's disease may differ in men and women: an exploratory study. Horm Behav. 2013 Feb;63(2):308-14. PubMed.

Primary Papers

  1. Savica R, Grossardt BR, Bower JH, Ahlskog JE, Rocca WA. Incidence and Pathology of Synucleinopathies and Tauopathies Related to Parkinsonism. JAMA Neurol. 2013 May 20;:1-7. PubMed.

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