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Copyright issues have stymied research on an old staple of cognitive function assessment, the mini-mental state examination (MMSE), researchers said.

Two groups of researchers who developed new tests that reportedly improved on the MMSE -- the Sweet-16, and the ACE-R -- have been asked to remove those tests from their websites by the company that manages copyright for the MMSE, Psychological Assessment Resources (PAR), according to , of the University of California San Francisco.

"This has a chilling effect on medical research," said Newman, who wrote a in this week's JAMA Internal Medicine. "I would be afraid as a young researcher. I wouldn't bet my career knowing I could get sued and lose 5 years of work."

PAR did not return requests for comment, nor did , of Beth Israel Deaconess Medical Medical Center in Boston, co-developer of the Sweet-16. , of Neuroscience Research Australia in Randwich, co-developer of the ACE-R, confirmed that the ACE-R was removed after a "long dispute" with PAR.

The change could also have an impact on clinical care, as physicians are technically required to purchase an MMSE form that costs $1.23 for each patient evaluated -- despite the fact that many can perform the 30-question battery from memory, Newman said.

Enforcing the Copyright

The MMSE had been freely available since its initial publication in 1975, but in 2000, its authors -- Marshal Folstein, MD, Susan Folstein, MD, and Paul McHugh, MD -- transferred the copyright to a company they founded, which then licensed the test to PAR in 2001. These authors could not be reached for comment.

There was little impact over the next 10 years, until March 2011 when Fong and colleagues published the Sweet-16 test and made it open-access so that all clinicians and researchers could use it. PAR claimed copyright violations, and the team pulled the test from its website.

More recently, the was withdrawn following . The group now offers the ACE-III instead, which has been validated and is open-access.

"We've learned a lot in 30 years, and we should be making efforts to make these tests faster, better, and more accurate," Newman said. "It's a problem for medical research."

The copyright issue not only poses a problem for researchers looking to improve upon the MMSE, he said. Researchers have switched to other tests for their studies, including the Mini-Cog and the Montreal Cognitive Assessment (MoCA).

That means 3 decades' worth of validation data on the MMSE are being lost. "Even though the MMSE is not perfect, we know a lot about how to use it and how it works in the population we're giving it to," Newman said. "It's a real hit to clinical practice to have to go and do all of this work over again with other tests."

Impact on Research and Practice

, of the University of Pittsburgh Medical Center but soon to start at the University of Florida, said most of his colleagues have switched to other tests "rather than have to either disobey the law or pay for access" to the MMSE.

"While the MMSE was not optimal for assessment of dementia -- that was not the purpose for which it was originally devised -- it had developed into a lingua franca, and clinicians understood that the MMSE scores could indicate whether a patient had mild, moderate, or severe disease," DeKosky said in an email to 乌鸦传媒. "Now there are several other screening tests in place; none are as familiar to many clinicians as the MMSE, and it will probably be a few years before we settle on standards and people know the 'meaning' of a particular score 'at a glance.'"

, of Mount Sinai Hospital in New York City, said that while her team has many alternatives to the MMSE, and that they often use more advanced neuropsychological tests, "we lose the familiarity" of MMSE results.

"The big loss to the community is that using a standardized tool that's established and well understood allows us to read about a population and know intuitively how they behave and what they look like, and it allows us to compare," Sano told 乌鸦传媒.

, of Massachusetts General Hospital in Boston, agreed that his team uses more advanced neuropsychological tests, but that the MMSE is "a good screening tool in general" and its diminishing use will have an impact on research.

Which Test to Use?

Researchers have been trying to get a handle on which tests are the best stand-ins for the MMSE. In the same issue of JAMA Internal Medicine, , of the Chinese University of Hong Kong, and colleagues conducted a of studies that evaluated some of the most common alternative cognitive assessments -- totaling 11 tests in 149 studies.

The MMSE was used in 102 of those studies. It had a sensitivity of 0.81 and a specificity of 0.89.

They found that the Mini-Cog and the ACE-R had the best diagnostic performances and were most comparable to the MMSE, with a sensitivity of 0.91 and a specificity of 0.86 for Mini-Cog, and a sensitivity of 0.92 and a specificity of 0.89 for ACE-R.

In a subgroup analysis, only the MoCA had comparable performance to the MMSE for mild cognitive impairment, with a sensitivity of 0.89 and a specificity of 0.75.

Legal Challenges

There has not yet been an official legal challenge on any of the copyright issues surrounding the MMSE. , of the University of California Hastings College of the Law in San Francisco, said the economics of cost and risk make clinicians and researchers pay the fee or switch tests.

She said the challenge wouldn't be likely to hold up in court because a test is a process, and processes are subject to a patent rather than to a copyright -- and that a test like this probably wouldn't be awarded a patent to begin with.

Still, the expense and potential risk of litigation would be enough to keep individual doctors from challenging it, Feldman said. Instead, a research organization, a consumer group, or some other public interest group would have to take it on.

"The real danger is in this practice spreading," she said. "If we Balkanize medical research in a way that copyright should never be applied, we do damage to patient care and research."

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