Research Letter
Life Expectancy for Patients With Sporadic Creutzfeldt-Jakob Disease
Amber Yaqub, MD1; A. Charlotte Menart, MD1; Bettina E. Hansen, PhD1; et al Author Affiliations Article Information
JAMA Neurol Published Online: July 28, 2025 doi: 10.1001/jamaneurol.2025.2495 related icon RELATED ARTICLESfigure icon FIGURESattach icon SUPPLEMENTAL CONTENT
Creutzfeldt-Jakob disease (CJD) is a rare, fatal neurodegenerative disorder caused by accumulation of misfolded prion proteins, affecting an estimated 1 to 2 individuals per million people annually.1 Sporadic CJD (sCJD) accounts for the majority of cases (85%-90%) and is characterized by a short life expectancy, with most patients dying within 5 to 6 months.2 Survival after onset of sCJD is known to vary, ranging from a few weeks for some patients to several years for others, but determinants of this variation in survival are not completely understood.2,3 Older patients with sCJD typically have shorter survival because of comorbidities, age-related changes in the brain, and reduced physiological reserve,4 yet age-specific models of life expectancy after sCJD onset are currently lacking.
Methods
We aimed to determine age-specific life expectancies for patients with sCJD using registry data collected from 1993 to 2022 from the Dutch National Surveillance Center of Creutzfeldt-Jakob Disease. Disease duration was determined by calculating the time difference (in weeks) between the onset of first symptoms and the date of death. Multistate life tables with 1-way transitions were used to estimate transition intensities, after which age-specific life expectancies were calculated. An extended description of these methods is noted in the eMethods in Supplement 1. Subsequently, we assessed which clinical variables were related to mortality after sCJD onset with Cox proportional hazard models, adjusting for age and sex. Finally, we analyzed trends in median survival over the past 30 years using time series methods, smoothing short-term fluctuations over time (k = 3).
Results We included 358 cases of sCJD confirmed by histopathology and/or real-time quaking-induced conversion test results. The mean (SD) age at onset of symptoms was 67.4 (9.1) years. Most patients had progressive dementia (96.9%), cerebellar signs (78.9%), myoclonus (67.7%), visual disturbances (51.2%), and extrapyramidal signs (51.2%). Life expectancy declined with increasing age: 22.0 weeks at age 65 years, 18.7 weeks at age 75 years, and 15.9 weeks at age 85 years (Figure 1). There were no statistically significant differences in life expectancy between men and women. Compared with cognitively healthy individuals, patients with sCJD lost nearly 100% of their expected remaining life span. The median (IQR) survival time after onset of sCJD was 11.8 (7.8-24.4) weeks, with akinetic mutism (hazard ratio [HR], 1.43; 95% CI, 1.10-1.84), triphasic wave complexes on electroencephalography (HR, 2.13; 95% CI, 1.70-2.68), a positive 14-3-3 test result (HR, 2.10; 95% CI, 1.43-3.09), and homozygosity at codon 129 of the PRNP gene (for Met/Met: HR, 2.84; 95% CI, 1.37-5.90; and for Val/Val: HR, 1.73; 95% CI, 0.59-5.04) being indicators of a poor prognosis. Despite an increase in sCJD incidence, the median survival time remained similar over the past 30 years and fluctuated around 12 weeks (Figure 2).
Figure 1. Age-Specific Life Expectancies for Patients After Onset of Sporadic Creutzfeldt-Jakob Disease
View LargeDownload
Age-Specific Life Expectancies for Patients After Onset of Sporadic Creutzfeldt-Jakob Disease(opens in new tab)
Figure 2. Median Survival Time and Rolling Average for Patients With Sporadic Creutzfeldt-Jakob Disease Over the Past 30 Years
View LargeDownload
Median Survival Time and Rolling Average for Patients With Sporadic Creutzfeldt-Jakob Disease Over the Past 30 Years(opens in new tab) Surveillance data were routinely assessed during the past 30 years. The moving average, computed with a time window of 3 years, is used in time series analysis to detect trends or patterns by smoothing out short-term fluctuations in the data.
Discussion
Life expectancy after sCJD onset is age dependent (Figure 1) and worse than reported in prior studies from western Europe2 and east Asia.3 Reasons for such discrepancies may include the application of different diagnostic criteria for sCJD, inclusion of probable cases, and options provided during end-of-life care. For instance, studies from Japan report longer survival because of extended palliative care, such as tube feeding during the akinetic mutism stage.5 Alternatively, there may be variations in the extent of neurodegeneration in neocortical or limbic regions between patients with sCJD, which is likely governed by the polymorphism at codon 129 of the PRNP gene.6 Because of limited availability of codon 129 data in the current study, this warrants further exploration.
Gaining insight into additional factors influencing life expectancy could pave the way for strategies to cope with the disease. Such efforts hold the potential to improve the quality of life for individuals affected by sCJD and their families, regardless of the duration of illness, be it weeks or months.
Article Information
Accepted for Publication: May 23, 2025.
Published Online: July 28, 2025. doi:10.1001/jamaneurol.2025.2495
Corresponding Author: M Arfan Ikram, MD, PhD, Department of Epidemiology, Erasmus MC – University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, the Netherlands (m.a.ikram@erasmusmc.nl).
Author Contributions: Drs Yaqub and Ikram had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Yaqub, Ikram. Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Yaqub.
Critical review of the manuscript for important intellectual content: All authors.
Statistical analysis: Yaqub, Hansen.
Obtained funding: Ikram.
Administrative, technical, or material support: Yaqub.
Supervision: Hansen, Ikram.
Other – suggestions and support during the drafting of the manuscript: Menart.
Conflict of Interest Disclosures: Dr Hansen reported grants from Ipsen, grants from Gilead, grants from Mirum, personal fees from Ipsen Advisor, personal fees from Gilead Advisor, personal fees from Mirum Advisor, personal fees from Pliant Advisor, personal fees from Advanz Advisor, and personal fees from Intercept Advisor outside the submitted work. No other disclosures were reported.
Funding/Support: The Dutch National Surveillance Registry is supported by the National Institute for Public Health and the Environment (Rijksinstituut voor Volksgezondheid en Milieu).
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 2.
Additional Contributions: We express our gratitude to the National Institute for Public Health and the Environment (Rijksinstituut voor Volksgezondheid en Milieu) for commissioning the Dutch National Surveillance Registry within the Department of Epidemiology at Erasmus Medical Center in Rotterdam and for granting permission to publish anonymized data for public health purposes. We also acknowledge the team of the Prion Laboratory, Department of Pathology, University Medical Center Utrecht, for their critical role in providing histopathological confirmation of suspected sCJD cases. Our appreciation extends to both the Prion Laboratory at UMC Utrecht and the Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Nijmegen (Translational Metabolic Laboratory), for conducting the real-time quaking-induced conversion tests for suspected sCJD cases. Finally, we are grateful to the patients with sCJD and their families, whose willingness to participate was not only fundamental to this study but also an invaluable contribution to advancing our understanding of this fatal disease.
References 1. Uttley L, Carroll C, Wong R, Hilton DA, Stevenson M. Creutzfeldt-Jakob disease: a systematic review of global incidence, prevalence, infectivity, and incubation. Lancet Infect Dis. 2020;20(1):e2-e10. doi. doi:10.1016/S1473-3099(19)30615-2PubMedGoogle ScholarCrossref
2. Pocchiari M, Puopolo M, Croes EA, et al. Predictors of survival in sporadic Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies. Brain. 2004;127(Pt 10):2348-2359. doi:10.1093/brain/awh249PubMedGoogle ScholarCrossref
3. Iwasaki Y, Akagi A, Mimuro M, Kitamoto T, Yoshida M. Factors influencing the survival period in Japanese patients with sporadic Creutzfeldt-Jakob disease. J Neurol Sci. 2015;357(1-2):63-68. doi. doi:10.1016/j.jns.2015.06.065PubMedGoogle ScholarCrossref
4. Appleby BS, Appleby KK, Rabins PV. Does the presentation of Creutzfeldt-Jakob disease vary by age or presumed etiology? a meta-analysis of the past 10 years. J Neuropsychiatry Clin Neurosci. 2007;19(4):428-435. doi. doi:10.1176/jnp.2007.19.4.428PubMedGoogle ScholarCrossref
5. Iwasaki Y, Mimuro M, Yoshida M, Kitamoto T, Hashizume Y. Survival to akinetic mutism state in Japanese cases of MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians. Eur J Neurol. 2011;18(7):999-1002. doi. doi:10.1111/j.1468-1331.2010.03185.xPubMedGoogle ScholarCrossref
6. Faucheux BA, Morain E, Diouron V, et al. Quantification of surviving cerebellar granule neurones and abnormal prion protein (PrPSc) deposition in sporadic Creutzfeldt-Jakob disease supports a pathogenic role for small PrPSc deposits common to the various molecular subtypes. Neuropathol Appl Neurobiol. 2011;37(5):500-512. doi:10.1111/j.1365-2990.2011.01179.xPubMedGoogle ScholarCrossref
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2001 Singeltary on CJD
JAMA. 2001;285(6):733-734. doi:10-1001/pubs.JAMA-ISSN-0098-7484-285-6-jlt0214
February 14, 2001
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Terry S. Singeltary, Sr
Author Affiliations
JAMA. 2001;285(6):733-734. doi:10-1001/pubs.JAMA-ISSN-0098-7484-285-6-jlt0214
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
Only registered and activated users can see links., Click Here To Register...
TUESDAY, APRIL 15, 2025
Cases of Creutzfeldt-Jakob disease in young individuals: open questions regarding aetiology
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TUESDAY, APRIL 15, 2025
Cases of Creutzfeldt-Jakob disease in young individuals: open questions regarding aetiology
Recently, two young individuals, aged 15 and 21, were diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD) in Canada and the United States, respectively (D'Arcy et al., 2019; Ahn et al., 2024).
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SUNDAY, MARCH 23, 2025
Creutzfeldt Jakob Disease TSE Prion Increasing 2025 Update
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Creutzfeldt Jakob Disease
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Iatrogenic Transmissible Spongiform Encephalopathy
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Life Expectancy for Patients With Sporadic Creutzfeldt-Jakob Disease
Amber Yaqub, MD1; A. Charlotte Menart, MD1; Bettina E. Hansen, PhD1; et al Author Affiliations Article Information
JAMA Neurol Published Online: July 28, 2025 doi: 10.1001/jamaneurol.2025.2495 related icon RELATED ARTICLESfigure icon FIGURESattach icon SUPPLEMENTAL CONTENT
Creutzfeldt-Jakob disease (CJD) is a rare, fatal neurodegenerative disorder caused by accumulation of misfolded prion proteins, affecting an estimated 1 to 2 individuals per million people annually.1 Sporadic CJD (sCJD) accounts for the majority of cases (85%-90%) and is characterized by a short life expectancy, with most patients dying within 5 to 6 months.2 Survival after onset of sCJD is known to vary, ranging from a few weeks for some patients to several years for others, but determinants of this variation in survival are not completely understood.2,3 Older patients with sCJD typically have shorter survival because of comorbidities, age-related changes in the brain, and reduced physiological reserve,4 yet age-specific models of life expectancy after sCJD onset are currently lacking.
Methods
We aimed to determine age-specific life expectancies for patients with sCJD using registry data collected from 1993 to 2022 from the Dutch National Surveillance Center of Creutzfeldt-Jakob Disease. Disease duration was determined by calculating the time difference (in weeks) between the onset of first symptoms and the date of death. Multistate life tables with 1-way transitions were used to estimate transition intensities, after which age-specific life expectancies were calculated. An extended description of these methods is noted in the eMethods in Supplement 1. Subsequently, we assessed which clinical variables were related to mortality after sCJD onset with Cox proportional hazard models, adjusting for age and sex. Finally, we analyzed trends in median survival over the past 30 years using time series methods, smoothing short-term fluctuations over time (k = 3).
Results We included 358 cases of sCJD confirmed by histopathology and/or real-time quaking-induced conversion test results. The mean (SD) age at onset of symptoms was 67.4 (9.1) years. Most patients had progressive dementia (96.9%), cerebellar signs (78.9%), myoclonus (67.7%), visual disturbances (51.2%), and extrapyramidal signs (51.2%). Life expectancy declined with increasing age: 22.0 weeks at age 65 years, 18.7 weeks at age 75 years, and 15.9 weeks at age 85 years (Figure 1). There were no statistically significant differences in life expectancy between men and women. Compared with cognitively healthy individuals, patients with sCJD lost nearly 100% of their expected remaining life span. The median (IQR) survival time after onset of sCJD was 11.8 (7.8-24.4) weeks, with akinetic mutism (hazard ratio [HR], 1.43; 95% CI, 1.10-1.84), triphasic wave complexes on electroencephalography (HR, 2.13; 95% CI, 1.70-2.68), a positive 14-3-3 test result (HR, 2.10; 95% CI, 1.43-3.09), and homozygosity at codon 129 of the PRNP gene (for Met/Met: HR, 2.84; 95% CI, 1.37-5.90; and for Val/Val: HR, 1.73; 95% CI, 0.59-5.04) being indicators of a poor prognosis. Despite an increase in sCJD incidence, the median survival time remained similar over the past 30 years and fluctuated around 12 weeks (Figure 2).
Figure 1. Age-Specific Life Expectancies for Patients After Onset of Sporadic Creutzfeldt-Jakob Disease
View LargeDownload
Age-Specific Life Expectancies for Patients After Onset of Sporadic Creutzfeldt-Jakob Disease(opens in new tab)
Figure 2. Median Survival Time and Rolling Average for Patients With Sporadic Creutzfeldt-Jakob Disease Over the Past 30 Years
View LargeDownload
Median Survival Time and Rolling Average for Patients With Sporadic Creutzfeldt-Jakob Disease Over the Past 30 Years(opens in new tab) Surveillance data were routinely assessed during the past 30 years. The moving average, computed with a time window of 3 years, is used in time series analysis to detect trends or patterns by smoothing out short-term fluctuations in the data.
Discussion
Life expectancy after sCJD onset is age dependent (Figure 1) and worse than reported in prior studies from western Europe2 and east Asia.3 Reasons for such discrepancies may include the application of different diagnostic criteria for sCJD, inclusion of probable cases, and options provided during end-of-life care. For instance, studies from Japan report longer survival because of extended palliative care, such as tube feeding during the akinetic mutism stage.5 Alternatively, there may be variations in the extent of neurodegeneration in neocortical or limbic regions between patients with sCJD, which is likely governed by the polymorphism at codon 129 of the PRNP gene.6 Because of limited availability of codon 129 data in the current study, this warrants further exploration.
Gaining insight into additional factors influencing life expectancy could pave the way for strategies to cope with the disease. Such efforts hold the potential to improve the quality of life for individuals affected by sCJD and their families, regardless of the duration of illness, be it weeks or months.
Article Information
Accepted for Publication: May 23, 2025.
Published Online: July 28, 2025. doi:10.1001/jamaneurol.2025.2495
Corresponding Author: M Arfan Ikram, MD, PhD, Department of Epidemiology, Erasmus MC – University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, the Netherlands (m.a.ikram@erasmusmc.nl).
Author Contributions: Drs Yaqub and Ikram had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Yaqub, Ikram. Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Yaqub.
Critical review of the manuscript for important intellectual content: All authors.
Statistical analysis: Yaqub, Hansen.
Obtained funding: Ikram.
Administrative, technical, or material support: Yaqub.
Supervision: Hansen, Ikram.
Other – suggestions and support during the drafting of the manuscript: Menart.
Conflict of Interest Disclosures: Dr Hansen reported grants from Ipsen, grants from Gilead, grants from Mirum, personal fees from Ipsen Advisor, personal fees from Gilead Advisor, personal fees from Mirum Advisor, personal fees from Pliant Advisor, personal fees from Advanz Advisor, and personal fees from Intercept Advisor outside the submitted work. No other disclosures were reported.
Funding/Support: The Dutch National Surveillance Registry is supported by the National Institute for Public Health and the Environment (Rijksinstituut voor Volksgezondheid en Milieu).
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 2.
Additional Contributions: We express our gratitude to the National Institute for Public Health and the Environment (Rijksinstituut voor Volksgezondheid en Milieu) for commissioning the Dutch National Surveillance Registry within the Department of Epidemiology at Erasmus Medical Center in Rotterdam and for granting permission to publish anonymized data for public health purposes. We also acknowledge the team of the Prion Laboratory, Department of Pathology, University Medical Center Utrecht, for their critical role in providing histopathological confirmation of suspected sCJD cases. Our appreciation extends to both the Prion Laboratory at UMC Utrecht and the Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Nijmegen (Translational Metabolic Laboratory), for conducting the real-time quaking-induced conversion tests for suspected sCJD cases. Finally, we are grateful to the patients with sCJD and their families, whose willingness to participate was not only fundamental to this study but also an invaluable contribution to advancing our understanding of this fatal disease.
References 1. Uttley L, Carroll C, Wong R, Hilton DA, Stevenson M. Creutzfeldt-Jakob disease: a systematic review of global incidence, prevalence, infectivity, and incubation. Lancet Infect Dis. 2020;20(1):e2-e10. doi. doi:10.1016/S1473-3099(19)30615-2PubMedGoogle ScholarCrossref
2. Pocchiari M, Puopolo M, Croes EA, et al. Predictors of survival in sporadic Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies. Brain. 2004;127(Pt 10):2348-2359. doi:10.1093/brain/awh249PubMedGoogle ScholarCrossref
3. Iwasaki Y, Akagi A, Mimuro M, Kitamoto T, Yoshida M. Factors influencing the survival period in Japanese patients with sporadic Creutzfeldt-Jakob disease. J Neurol Sci. 2015;357(1-2):63-68. doi. doi:10.1016/j.jns.2015.06.065PubMedGoogle ScholarCrossref
4. Appleby BS, Appleby KK, Rabins PV. Does the presentation of Creutzfeldt-Jakob disease vary by age or presumed etiology? a meta-analysis of the past 10 years. J Neuropsychiatry Clin Neurosci. 2007;19(4):428-435. doi. doi:10.1176/jnp.2007.19.4.428PubMedGoogle ScholarCrossref
5. Iwasaki Y, Mimuro M, Yoshida M, Kitamoto T, Hashizume Y. Survival to akinetic mutism state in Japanese cases of MM1-type sporadic Creutzfeldt-Jakob disease is similar to Caucasians. Eur J Neurol. 2011;18(7):999-1002. doi. doi:10.1111/j.1468-1331.2010.03185.xPubMedGoogle ScholarCrossref
6. Faucheux BA, Morain E, Diouron V, et al. Quantification of surviving cerebellar granule neurones and abnormal prion protein (PrPSc) deposition in sporadic Creutzfeldt-Jakob disease supports a pathogenic role for small PrPSc deposits common to the various molecular subtypes. Neuropathol Appl Neurobiol. 2011;37(5):500-512. doi:10.1111/j.1365-2990.2011.01179.xPubMedGoogle ScholarCrossref
Only registered and activated users can see links., Click Here To Register... &utm_campaign=article_alert-jamaneurology&utm_content=olf-recommended-tfl_&utm_term=080425
2001 Singeltary on CJD
JAMA. 2001;285(6):733-734. doi:10-1001/pubs.JAMA-ISSN-0098-7484-285-6-jlt0214
February 14, 2001
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Terry S. Singeltary, Sr
Author Affiliations
JAMA. 2001;285(6):733-734. doi:10-1001/pubs.JAMA-ISSN-0098-7484-285-6-jlt0214
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
Only registered and activated users can see links., Click Here To Register...
TUESDAY, APRIL 15, 2025
Cases of Creutzfeldt-Jakob disease in young individuals: open questions regarding aetiology
Only registered and activated users can see links., Click Here To Register...
TUESDAY, APRIL 15, 2025
Cases of Creutzfeldt-Jakob disease in young individuals: open questions regarding aetiology
Recently, two young individuals, aged 15 and 21, were diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD) in Canada and the United States, respectively (D'Arcy et al., 2019; Ahn et al., 2024).
Only registered and activated users can see links., Click Here To Register...
Only registered and activated users can see links., Click Here To Register...
SUNDAY, MARCH 23, 2025
Creutzfeldt Jakob Disease TSE Prion Increasing 2025 Update
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Creutzfeldt Jakob Disease
Only registered and activated users can see links., Click Here To Register...
Iatrogenic Transmissible Spongiform Encephalopathy
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terry