As with so many of my posts, the staring point for this post is the paper by Willis et al. [1]. It contains, amongst other things, maps of the US, at a county-by-county level, showing the distribution of the incidence and prevalence of Parkinson's among Medicare beneficiaries. The data is age and ethnically normalized.

Incidence: http://www.ncbi.nlm.nih.gov/pmc/arti...395/figure/F2/

Prevalence: http://www.ncbi.nlm.nih.gov/pmc/arti...395/figure/F1/

To my eyes, the key feature of these maps is the under representation of Parkinson's in the west coast and Rocky Mountain states and an over representation in a band from the Texas coast north eastwards to the Canadian border. In particular, areas close to the Mississippi and Ohio rivers seem to have high incidence.

I've searched the internet for any form of data which has a similar distribution. (I don't have access to the raw PD data, so I've not been able to use statistical techniques. My approach has been to simply "eye-ball" the maps.)

I've posted on apparent correlations (which may or may not be causal) between PD and:
- surface ozone [2];
- atmospheric nitric oxide [2];
- air quality [3].

I've now extended my search to look for biological entities with similar distributions to PD. One that has jumped out is the fungus histoplasma capsulatum, which causes a disease called histoplasmosis.

The paper by Baddley et al. [4] shows the incidence of histoplasmosis in people over 65: http://www.ncbi.nlm.nih.gov/pmc/arti...071/figure/F1/

The correlation between PD and histoplasmosis is far from perfect. For instance South Dakota is high for histoplasmosis, but low for PD. Also, histoplasmosis is rare in areas further than 45 degrees from the equator, so it is unlikely to play a large role in PD in, for instance, the UK.

The symptoms of histoplasmosis are:
"Many people who are infected with the fungus do not show any symptoms. In areas of the world where the fungus is very common in the environment, many people may have been infected with Histoplasma capsulatum without having any symptoms. If symptoms occur, they usually start within 3 to 17 days after being exposed to the fungus.

In people who develop disease, the most common symptoms are similar to those of pneumonia, and include: fever, chest pains, and a dry or nonproductive cough. Some people may also experience joint pain. If the disease is not treated, it can disseminate (spread) from the lungs to other organs." [5]

Histoplasmosis can be chronic. It can affect the brain.

Wu-Hsieh et al. write [6]:
"Experimental infection of animals with Histoplasma capsulatum caused a massive macrophage infiltration into the spleen and induced the production of tumor necrosis factor alpha (TNF-alpha) locally."

Mogi et al. write [7]:
"Tumor necrosis factor-alpha (TNF-alpha), a glial-cell-related factor, was
measured for the first time in the brain (striatum) and cerebrospinal fluid
(CSF) from control and parkinsonian patients by a sensitive sandwich enzyme
immunoassay. The concentrations of TNF-alpha in the brain and CSF were
significantly higher in parkinsonian patients than those in controls. Since
TNF-alpha is an important signal transducer of the immune system with cytotoxic and stimulator properties, these results suggest that an immune response may occur in the nigrostriatal dopaminergic regions in Parkinson's disease and that TNF-alpha may be related, at least in part, to the neuronal degeneration."

Given the above evidence, albeit circumstantial, it seems to me that histoplasma capsulatum could possibly be a cause of some cases of Parkinson's. If so, anti-fungals might help some people.


References

[1] "Geographic and Ethnic Variation in Parkinson Disease: A Population-Based

Study of US Medicare Beneficiaries"
Allison Wright Willis, Bradley A. Evanoff, Min Lian, Susan R. Criswell, and Brad

A. Racette
Neuroepidemiology. 2010 April; 34(3); 143-151.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2865395/

[2] http://neurotalk.psychcentral.com/thread113014.html

[3] http://neurotalk.psychcentral.com/thread113014-2.html

[4] "Geographic distribution of endemic fungal infections among older persons,

United States"
Baddley JW, Winthrop KL, Patkar NM, Delzell E, Beukelman T, Xie F, et al.
Emerg Infect Dis. 2011 Sep
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322071/

[5] http://www.cdc.gov/fungal/histoplasmosis/symptoms.html

[6] "Early activation of splenic macrophages by tumor necrosis factor alpha is
important in determining the outcome of experimental histoplasmosis in mice."
Wu-Hsieh et al.
Infect Immun 1992 Oct; 60(10);4230-4238
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC257457/

[7] "Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients."
Mogi M. et al.
Neurosci Lett, 1994 Jan 3; 165(1-2):208-210
http://www.ncbi.nlm.nih.gov/pubmed/8015728

John