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SEATTLE -- The incidence of Creutzfeldt-Jakob disease (CJD), the spongiform brain malady, rose by more than half in the U.S. from 2000 to 2014, according to a new study reported here, although the reasons for the increase remain unclear.

People were hospitalized for CJD at a rate of 1.6 per million persons in 2000 (95% CI 1.2-2.0), reported Alison Seitz, MD, of NewYork-Presbyterian Hospital in New York City, during a recorded platform presentation at the American Academy of Neurology annual meeting.

By 2014, she said, the rate had reached 2.7 per million (95% CI 2.2-3.2), for an average annual increase of 4.6%.

Importantly, her analysis did not adjust for the U.S. population's changing age distribution, which of course became older on average during the study period. (Seitz told 番茄社区app that further analyses, including age adjustment, are still in process.) Because "sporadic" CJD, accounting for 80% to 95% of all cases, is most common in older people, some increase in crude incidence rates would be expected in an aging population.

But growth in the older demographic has been considerably less than 4.6% annually -- more like 2% to 3%, according to a from the federal Administration for Community Living. That suggests something else is going on besides an increasingly top-heavy age pyramid.

Seitz noted that one possibility is simply increased attention to the presence of CJD. As it happens, 1993 was the year before "mad cow disease" exploded into the world's headlines. infected with bovine spongiform encephalopathy were detected in the U.K. in 1994, sparking a global panic. A few cases also occurred in the U.S., although against the background of naturally occurring CJD, they .

Yet those same data also suggested a substantial increase in overall CJD fatalities starting in about 2000. The CDC gets its data primarily from death certificates. Seitz and colleagues decided to draw on a different data source, the (NIS), which might be more accurate considering all the known issues with death certificates. For one thing, the NIS has more complete information about the patients registered, including a full accounting of ICD diagnostic codes recorded for each individual. For the current study, the researchers searched for the codes 046.1, 046.11, and 046.19 to capture CJD cases.

Another nice feature of the NIS is that, while it doesn't cover all U.S. hospitalizations -- "it is a sample," Seitz observed, with about 8 million patient encounters per year -- the summary data are weighted to match overall population characteristics.

Thus, the 1,837 CJD hospitalizations identified in the 2000-2014 NIS data extrapolate to 8,778 overall in the U.S. during the period, Seitz said.

The overall upward trend over time wasn't steady. A spike in 2008 was bracketed by years of sharp decreases, for example. Moreover, these year-to-year changes weren't exactly matched in the CDC's mortality data, although CJD is uniformly fatal and usually within a year of diagnosis.

Seitz also cited the possibility that hospital registrars have gotten freer with the codes for CJD, "appropriately or not," as another potential explanation for the increased incidence in NIS data.

One potentially relevant factor Seitz didn't mention is (CWD), the prion-caused pathology affecting deer, elk, and related animals. The CDC says no confirmed cases of cervid-to-human transmission are known. Nevertheless, the condition has been spreading in wild deer and elk over the past two decades, now spanning "at least 27 states" in the Midwest, South, and East Coast, according to the agency's .

In 2021, are estimated to have been killed and presumably handled by hunters, so contact with infected animals seems likely, and likely to have grown over the period covered by the new study. Seitz told 番茄社区app that, if CWD was a factor, one might expect that incidence rates would be higher in states where CWD is endemic. "We haven't considered doing a geographic analysis, but now you're making me think maybe we should try," she wrote in an email.

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