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  • Review Article
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Rapidly progressive dementias — aetiologies, diagnosis and management

Nature Reviews Neurology volume 18, pages 363–376 (2022)Cite this article

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Abstract

Rapidly progressive dementias (RPDs) are a group of heterogeneous disorders that include immune-mediated, infectious and metabolic encephalopathies, as well as prion diseases and atypically rapid presentations of more common neurodegenerative diseases. Some of these conditions are treatable, and some must be diagnosed promptly because of their potential infectivity. Prion disease is considered to be the prototypical RPD, but over the past two decades, epidemiological reports and the identification of various encephalitis-mediating antibodies have led to a growing recognition of other encephalopathies as potential causes of rapid cognitive decline. Knowledge of RPD aetiologies, syndromes and diagnostic work-up protocols will help clinicians to establish an early, accurate diagnosis, thereby reducing morbidity and mortality, especially in immune-mediated and other potentially reversible dementias. In this Review, we define the syndrome of RPD and shed light on its different aetiologies and on secondary factors that might contribute to rapid cognitive decline. We describe an extended diagnostic procedure in the context of important differential diagnoses, discuss the utility of biomarkers and summarize potential treatment options. In addition, we discuss treatment options such as high-dose steroid therapy in the context of therapy and diagnosis in clinically ambiguous cases.

Key points

  • Definitions of rapidly progressive dementia (RPD) vary according to the aetiological background and relate to the speed of cognitive decline, time from first symptom to dementia syndrome and/or overall survival.

  • RPD can occur in rapidly progressive neurodegenerative diseases, such as prion diseases, or in primarily slowly progressive diseases as a consequence of intrinsic factors or concomitant pathologies.

  • Besides neurodegenerative diseases, inflammatory (immune-mediated and infectious), vascular, metabolic and neoplastic CNS diseases are important and frequent causes of RPD.

  • To identify treatable causes of RPD, the technical diagnostic work-up must include MRI and analyses of blood and cerebrospinal fluid, and further diagnostics might be indicated in unclear cases.

  • Therapeutic options for many non-neurodegenerative causes of RPD are already available; disease-modifying therapies for neurodegenerative RPDs are an important focus of current research and could become a treatment option in the near future.

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Fig. 1: Rapidly progressive dementia: disease entities and contributing factors.
Fig. 2: Probable rapidly progressive dementia aetiologies in relation to time from onset to dementia.
Fig. 3: MRI findings in rapidly progressive dementia.

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References

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th edn (American Psychiatric Association, 1994).

  2. Geschwind, M. D. Rapidly progressive dementia. Continuum 22, 510–537 (2016).

    PubMed  PubMed Central  Google Scholar 

  3. Masters, C. L. et al. Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering. Ann. Neurol. 5, 177–188 (1979).

    Article  CAS  PubMed  Google Scholar 

  4. Dalmau, J. & Graus, F. Antibody-mediated encephalitis. N. Engl. J. Med. 378, 840–851 (2018).

    Article  PubMed  Google Scholar 

  5. Soto, M. E. et al. Rapid cognitive decline in Alzheimer’s disease. Consensus paper. J. Nutr. Health Aging 12, 703–713 (2008).

    CAS  PubMed  Google Scholar 

  6. Chitravas, N. et al. Treatable neurological disorders misdiagnosed as Creutzfeldt-Jakob disease. Ann. Neurol. 70, 437–444 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Mead, S. & Rudge, P. CJD mimics and chameleons. Pract. Neurol. 17, 113–121 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Geschwind, M. D. & Murray, K. Differential diagnosis with other rapid progressive dementias in human prion diseases. Handb. Clin. Neurol. 153, 371–397 (2018).

    Article  PubMed  Google Scholar 

  9. Zerr, I. & Hermann, P. Diagnostic challenges in rapidly progressive dementia. Expert. Rev. Neurother. 18, 761–772 (2018).

    Article  CAS  PubMed  Google Scholar 

  10. Watson, N. et al. The importance of ongoing international surveillance for Creutzfeldt–Jakob disease. Nat. Rev. Neurol. 17, 362–379 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Woodruff, B. K. Evaluation of rapidly progressive dementia. Semin. Neurol. 27, 363–375 (2007).

    Article  PubMed  Google Scholar 

  12. Geschwind, M. D., Haman, A. & Miller, B. L. Rapidly progressive dementia. Neurol. Clin. 25, 783–807 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Geschwind, M. D., Shu, H., Haman, A., Sejvar, J. J. & Miller, B. L. Rapidly progressive dementia. Ann. Neurol. 64, 97–108 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Appleby, B. S. & Lyketsos, C. G. Rapidly progressive dementias and the treatment of human prion diseases. Expert. Opin. Pharmacother. 12, 1–12 (2011).

    Article  CAS  PubMed  Google Scholar 

  15. Rosenbloom, M. H. & Atri, A. The evaluation of rapidly progressive dementia. Neurologist 17, 67–74 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mahajan, S. & Appleby, B. S. Comprehensive and methodical: diagnostic and management approaches to rapidly progressive dementia. Curr. Treat. Options Neurol. 19, 40 (2017).

    Article  PubMed  Google Scholar 

  17. Bergin, J. D. Rapidly progressing dementia in disseminated sclerosis. J. Neurol. Neurosurg. Psychiatry 20, 285–292 (1957).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zerr, I. et al. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Brain 132, 2659–2668 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Josephs, K. A. et al. Rapidly progressive neurodegenerative dementias. Arch. Neurol. 66, 201–207 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Schmidt, C. et al. Rapidly progressive Alzheimer disease. Arch. Neurol. 68, 1124–1130 (2011).

    Article  PubMed  Google Scholar 

  21. Gaig, C. et al. Rapidly progressive diffuse Lewy body disease. Mov. Disord. 26, 1316–1323 (2011).

    Article  PubMed  Google Scholar 

  22. Degnan, A. J. & Levy, L. M. Neuroimaging of rapidly progressive dementias, part 1: neurodegenerative etiologies. Am. J. Neuroradiol. 35, 418–423 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Garcia-Esparcia, P. et al. Dementia with Lewy bodies: molecular pathology in the frontal cortex in typical and rapidly progressive forms. Front. Neurol. 8, 89 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Neto, A. S. et al. Rapidly progressive dementia: prevalence and causes in a neurologic unit of a tertiary hospital in Brazil. Alzheimer Dis. Assoc. Disord. 31, 239–243 (2017).

    Article  Google Scholar 

  25. Papageorgiou, S. G. et al. Rapidly progressive dementia: causes found in a Greek tertiary referral center in Athens. Alzheimer Dis. Assoc. Disord. 23, 337–346 (2009).

    Article  PubMed  Google Scholar 

  26. Anuja, P. et al. Rapidly progressive dementia: an eight year (2008–2016) retrospective study. PLoS ONE 13, e0189832 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  27. GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 18, 459–480 (2019).

    Article  Google Scholar 

  28. Day, G. S., Musiek, E. S. & Morris, J. C. Rapidly progressive dementia in the outpatient clinic: more than prions. Alzheimer Dis. Assoc. Disord. 32, 291–297 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Stoeck, K. et al. Cerebrospinal fluid biomarker supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias: a longitudinal multicentre study over 10 years. Brain 135, 3051–3061 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Peckeu, L. et al. Accuracy of diagnosis criteria in patients with suspected diagnosis of sporadic Creutzfeldt-Jakob disease and detection of 14-3-3 protein, France, 1992 to 2009. Eur. Surveill. 22, 16-00715 (2017).

    Article  Google Scholar 

  31. Grau-Rivera, O. et al. Clinicopathological correlations and concomitant pathologies in rapidly progressive dementia: a brain bank series. Neurodegener. Dis. 15, 350–360 (2015).

    Article  CAS  PubMed  Google Scholar 

  32. Maat, P. et al. Pathologically confirmed autoimmune encephalitis in suspected Creutzfeldt-Jakob disease. Neurol. Neuroimmunol. Neuroinflamm 2, e178 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Sala, I. et al. Rapidly progressive dementia: experience in a tertiary care medical center. Alzheimer Dis. Assoc. Disord. 26, 267–271 (2012).

    Article  PubMed  Google Scholar 

  34. Zhang, Y., Gao, T. & Tao, Q. Q. Spectrum of noncerebrovascular rapidly progressive cognitive deterioration: a 2-year retrospective study. Clin. Interv. Aging 12, 1655–1659 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Acosta, J. N. et al. Diagnosis of rapidly progressive dementia in a referral center in Argentina. Alzheimer Dis. Assoc. Disord. 34, 54–58 (2020).

    Article  PubMed  Google Scholar 

  36. Hermann, P. et al. Validation and utilization of amended diagnostic criteria in Creutzfeldt-Jakob disease surveillance. Neurology 91, e331–e338 (2018).

    Article  PubMed  Google Scholar 

  37. Uttley, L., Carroll, C., Wong, R., Hilton, D. A. & Stevenson, M. Creutzfeldt-Jakob disease: a systematic review of global incidence, prevalence, infectivity, and incubation. Lancet Infect. Dis. 20, e2–e10 (2020).

    Article  PubMed  Google Scholar 

  38. Parchi, P. et al. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann. Neurol. 46, 224–233 (1999).

    Article  CAS  PubMed  Google Scholar 

  39. Baiardi, S. et al. Towards an early clinical diagnosis of sporadic CJD VV2 (ataxic type). J. Neurol. Neurosurg. Psychiatry 88, 764–772 (2017).

    Article  PubMed  Google Scholar 

  40. Krasnianski, A. et al. Clinical findings and diagnostic tests in the MV2 subtype of sporadic CJD. Brain 129, 2288–2296 (2006).

    Article  PubMed  Google Scholar 

  41. Meissner, B. et al. Sporadic Creutzfeldt-Jakob disease: clinical and diagnostic characteristics of the rare VV1 type. Neurology 65, 1544–1550 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Puoti, G. et al. Sporadic human prion diseases: molecular insights and diagnosis. Lancet Neurol. 11, 618–628 (2012).

    Article  CAS  PubMed  Google Scholar 

  43. Krasnianski, A. et al. Clinical features and diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease. Arch. Neurol. 63, 876–880 (2006).

    Article  PubMed  Google Scholar 

  44. Alvarez, F. J., Bisbe, J., Bisbe, V. & Dávalos, A. Magnetic resonance imaging findings in pre-clinical Creutzfeldt-Jakob disease. Int. J. Neurosci. 115, 1219–1225 (2005).

    Article  CAS  PubMed  Google Scholar 

  45. Satoh, K. et al. Early detection of sporadic CJD by diffusion-weighted MRI before the onset of symptoms. J. Neurol. Neurosurg. Psychiatry 82, 942–943 (2011).

    Article  PubMed  Google Scholar 

  46. Vitali, P. et al. Diffusion-weighted MRI hyperintensity patterns differentiate CJD from other rapid dementias. Neurology 76, 1711–1719 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hermann, P. et al. Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease. Lancet Neurol. 20, 235–246 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. McGuire, L. I. et al. Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease. Ann. Neurol. 72, 278–285 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Rhoads, D. et al. Diagnosis of prion diseases by RT-QuIC results in improved surveillance. Neurology 95, e1017–e1026 (2020).

    Article  CAS  PubMed  Google Scholar 

  50. Heinemann, U. et al. Creutzfeldt-Jakob disease in Germany: a prospective 12-year surveillance. Brain 130, 1350–1359 (2007).

    Article  CAS  PubMed  Google Scholar 

  51. Gelpi, E. et al. Creutzfeldt-Jakob disease in Austria: an autopsy-controlled study. Neuroepidemiology 30, 215–221 (2008).

    Article  PubMed  Google Scholar 

  52. Abu-Rumeileh, S., Capellari, S. & Parchi, P. Rapidly progressive Alzheimer’s disease: contributions to clinical-pathological definition and diagnosis. J. Alzheimers Dis. 63, 887–897 (2018).

    Article  PubMed  Google Scholar 

  53. Hecht, M., Krämer, L. M., von Arnim, C. A. F., Otto, M. & Tal, D. R. Capillary cerebral amyloid angiopathy in Alzheimer’s disease: association with allocortical/hippocampal microinfarcts and cognitive decline. Acta Neuropathol. 135, 681–694 (2018).

    Article  CAS  PubMed  Google Scholar 

  54. Schmidt, C. et al. Clinical features of rapidly progressive Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. 29, 371–378 (2010).

    Article  CAS  PubMed  Google Scholar 

  55. Seidl, J. N. & Massman, P. J. Rapidly versus slowly progressing patients with Alzheimer’s disease: differences in baseline cognition. Am. J. Alzheimers Dis. Other Dement 31, 318–325 (2016).

    Article  Google Scholar 

  56. Tosto, G. et al. Neuropsychological predictors of rapidly progressive Alzheimer’s disease. Acta Neurol. Scand. 132, 417–422 (2015).

    Article  CAS  PubMed  Google Scholar 

  57. Ba, M. et al. The prevalence and biomarkers’ characteristic of rapidly progressive Alzheimer’s disease from the Alzheimer’s Disease Neuroimaging Initiative database. Alzheimers Dement. 3, 107–113 (2017).

    Article  Google Scholar 

  58. Cohen, M. L. et al. Rapidly progressive Alzheimer’s disease features distinct structures of amyloid-β. Brain 138, 1009–1022 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Liu, H. et al. Distinct conformers of amyloid beta accumulate in the neocortex of patients with rapidly progressive Alzheimer’s disease. J. Biol. Chem. 29, 101267 (2021).

    Article  Google Scholar 

  60. Qiang, W., Yau, W. M., Lu, J. X., Collinge, J. & Tycko, R. Structural variation in amyloid-β fibrils from Alzheimer’s disease clinical subtypes. Nature 541, 217–221 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Noor, A. et al. Molecular profiles of amyloid-β proteoforms in typical and rapidly progressive Alzheimer’s disease. Mol. Neurobiol. 59, 17–34 (2022).

    Article  CAS  PubMed  Google Scholar 

  62. Drummond, E. et al. Proteomic differences in amyloid plaques in rapidly progressive and sporadic Alzheimer’s disease. Acta Neuropathol. 133, 933–954 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Shafiq, M. et al. Prion protein oligomers cause neuronal cytoskeletal damage in rapidly progressive Alzheimer’s disease. Mol. Neurodegener. 6, 11 (2021).

    Article  Google Scholar 

  64. Younas, N. et al. SFPQ and Tau: critical factors contributing to rapid progression of Alzheimer’s disease. Acta Neuropathol. 140, 317–339 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kim, C. et al. Distinct populations of highly potent TAU seed conformers in rapidly progressing Alzheimer’s disease. Sci. Transl. Med. 14, eabg0253 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Graff-Radford, J. et al. Duration and pathologic correlates of Lewy body disease. JAMA Neurol. 74, 310–315 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Geut, H. et al. Neuropathological and genetic characteristics of a post-mortem series of cases with dementia with Lewy bodies clinically suspected of Creutzfeldt-Jakob’s disease. Parkinsonism Relat. Disord. 63, 162–168 (2019).

    Article  CAS  PubMed  Google Scholar 

  68. Coyle-Gilchrist, I. T. et al. Prevalence, characteristics, and survival of frontotemporal lobar degeneration syndromes. Neurology 86, 1736–1743 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Josephs, K. A. et al. Survival in two variants of tau-negative frontotemporal lobar degeneration: FTLD-U vs FTLD-MND. Neurology 65, 645–647 (2005).

    Article  CAS  PubMed  Google Scholar 

  70. Moore, K. M. et al. Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study. Lancet Neurol. 19, 145–156 (2020).

    Article  CAS  PubMed  Google Scholar 

  71. Skrobot, O. A. et al. Progress toward standardized diagnosis of vascular cognitive impairment: guidelines from the Vascular Impairment of Cognition Classification Consensus Study. Alzheimers Dement. 14, 280–292 (2018).

    Article  PubMed  Google Scholar 

  72. Gatti, L. et al. Understanding the pathophysiology of cerebral amyloid angiopathy. Int. J. Mol. Sci. 21, 3435 (2020).

    Article  CAS  PubMed Central  Google Scholar 

  73. Chung, C. P. et al. Cerebral microbleed burdens in specific brain regions are associated with disease severity of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J. Am. Heart Assoc. 9, e016233 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Gao, B., Lyu, C., Lerner, A. & McKinney, A. M. Controversy of posterior reversible encephalopathy syndrome: what have we learnt in the last 20 years? J. Neurol. Neurosurg. Psychiatry 89, 14–20 (2018).

    Article  PubMed  Google Scholar 

  75. Salvarani, C., Brown, R. D. Jr & Hunder, G. G. Adult primary central nervous system vasculitis. Lancet 9843, 767–777 (2012).

    Article  Google Scholar 

  76. Schuster, S. et al. Relapse rates and long-term outcome in primary angiitis of the central nervous system. J. Neurol. 266, 1481–1489 (2019).

    Article  PubMed  Google Scholar 

  77. John, S. & Hajj-Ali, R. A. CNS vasculitis. Semin. Neurol. 34, 405–412 (2014).

    Article  PubMed  Google Scholar 

  78. Salvarani, C. et al. Aβ-related angiitis: comparison with CAA without inflammation and primary CNS vasculitis. Neurology 81, 1596–1603 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Schneider, J. A., Arvanitakis, Z., Bang, W. & Bennett, D. A. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 69, 2197–2204 (2007).

    Article  PubMed  Google Scholar 

  80. Dubois, B. et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 13, 614–629 (2014).

    Article  PubMed  Google Scholar 

  81. Ramachandran, P. S. et al. Neurosyphilis: still prevalent and overlooked in an at risk population. PLoS ONE 15, e0238617 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Tang, W. et al. Late neurosyphilis and tertiary syphilis in Guangdong Province, China: results from a cross-sectional study. Sci. Rep. 7, 45339 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Ghanem, K. G., Ram, S. & Rice, P. A. The modern epidemic of syphilis. N. Engl. J. Med. 382, 845–854 (2020).

    Article  PubMed  Google Scholar 

  84. Granerod, J. et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect. Dis. 10, 835–844 (2010).

    Article  PubMed  Google Scholar 

  85. Boucher, A. et al. Epidemiology of infectious encephalitis causes in 2016. Med. Mal. Infect. 47, 221–235 (2017).

    Article  CAS  PubMed  Google Scholar 

  86. Wang, Y. et al. Global prevalence and burden of HIV-associated neurocognitive disorder: a meta-analysis. Neurology 95, e2610–e2621 (2020).

    Article  CAS  PubMed  Google Scholar 

  87. Compain, C. et al. Central nervous system involvement in Whipple disease: clinical study of 18 patients and long-term follow-up. Medicine 92, 324–330 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Turtle, L. & Solomon, T. Japanese encephalitis–the prospects for new treatments. Nat. Rev. Neurol. 14, 298–313 (2018).

    Article  PubMed  Google Scholar 

  89. Niller, H. H. et al. Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999-2019: an epidemiological investigation. Lancet Infect. Dis. 20, 467–477 (2020).

    Article  CAS  PubMed  Google Scholar 

  90. Berger, J. R. et al. PML diagnostic criteria: consensus statement from the AAN Neuroinfectious Disease Section. Neurology 80, 1430–1438 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Helms, J. et al. Neurologic features in severe SARS-CoV-2 infection. N. Engl. J. Med. 382, 2268–2270 (2020).

    Article  PubMed  Google Scholar 

  92. Paterson, R. W. et al. The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain 143, 3104–3120 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Frontera, J. A. et al. A prospective study of neurologic disorders in hospitalized patients with COVID-19 in New York City. Neurology 96, e575–e586 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Young, M. J., O’Hare, M., Matiello, M. & Schmahmann, J. D. Creutzfeldt-Jakob disease in a man with COVID-19: SARS-CoV-2-accelerated neurodegeneration? Brain Behav. Immun. 89, 601–603 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Baker, H. A., Safavynia, S. A. & Evered, L. A. The ‘third wave’: impending cognitive and functional decline in COVID-19 survivors. Br. J. Anaesth. 126, 44–47 (2021).

    Article  CAS  PubMed  Google Scholar 

  96. Arnold, C. Could COVID delirium bring on dementia? Nature 588, 22–24 (2020).

    Article  PubMed  Google Scholar 

  97. Numbers, K. & Brodaty, H. The effects of the COVID-19 pandemic on people with dementia. Nat. Rev. Neurol. 17, 69–70 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Watson, N. et al. Application of telehealth for comprehensive Creutzfeldt-Jakob disease surveillance in the United Kingdom. J. Neurol. Sci. 420, 117221 (2021).

    Article  CAS  PubMed  Google Scholar 

  99. Lancaster, E. & Dalmau, J. Neuronal autoantigens–pathogenesis, associated disorders and antibody testing. Nat. Rev. Neurol. 8, 380–390 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Hansen, N. et al. Autoantibody-associated psychiatric symptoms and syndromes in adults: a narrative review and proposed diagnostic approach. Brain Behav. Immun. Health 9, 100154 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  101. Geschwind, M. D. et al. Voltage-gated potassium channel autoimmunity mimicking Creutzfeldt-Jakob disease. Arch. Neurol. 65, 1341–1346 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  102. Sabater, L. et al. A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study. Lancet Neurol. 13, 575–586 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Do, L. D. et al. Characteristics in limbic encephalitis with anti-adenylate kinase 5 autoantibodies. Neurology 88, 514–524 (2017).

    Article  CAS  PubMed  Google Scholar 

  104. Ricken, G. et al. Autoimmune global amnesia as manifestation of AMPAR encephalitis and neuropathologic findings. Neurol. Neuroimmunol. Neuroinflamm 8, e1019 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  105. Escudero, D. et al. Antibody-associated CNS syndromes without signs of inflammation in the elderly. Neurology 89, 1471–1475 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  106. Graus, F. et al. Syndrome and outcome of antibody-negative limbic encephalitis. Eur. J. Neurol. 25, 1011–1016 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Gozzard, P. et al. Paraneoplastic neurologic disorders in small cell lung carcinoma: a prospective study. Neurology 85, 235–239 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Armangue, T. et al. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol. 17, 760–772 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Titulaer, M. J. et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 12, 157–165 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Valencia-Sanchez, C. et al. Brain dysfunction and thyroid antibodies: autoimmune diagnosis and misdiagnosis. Brain Commun. 3, fcaa233 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  111. Picard, C., Pasquier, F., Martinaud, O., Hannequin, D. & Godefroy, O. Early onset dementia: characteristics in a large cohort from academic memory clinics. Alzheimer Dis. Assoc. Disord. 25, 203–205 (2011).

    Article  PubMed  Google Scholar 

  112. Hillbom, M., Pieninkeroinen, I. & Leone, M. Seizures in alcohol-dependent patients: epidemiology, pathophysiology and management. CNS Drugs 17, 1013–1030 (2003).

    Article  CAS  PubMed  Google Scholar 

  113. Panda, A. K. & Malik, S. CNS intravascular lymphoma: an underappreciated cause of rapidly progressive dementia. BMJ Case Rep. 2014, bcr2014203772 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  114. Van der Meulen, M. et al. Cognitive functioning and health-related quality of life in patients with newly diagnosed primary CNS lymphoma: a systematic review. Lancet Oncol. 19, e407–e418 (2018).

    Article  PubMed  Google Scholar 

  115. Van der Meulen, M. et al. Neurocognitive functioning and radiologic changes in primary CNS lymphoma patients: results from the HOVON 105/ALLG NHL 24 randomized controlled trial. Neuro Oncol. 23, 1315–1326 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  116. El-Hattab, A. W., Adesina, A. M., Jones, J. & Scaglia, F. MELAS syndrome: clinical manifestations, pathogenesis, and treatment options. Mol. Genet. Metab. 116, 4–12 (2015).

    Article  CAS  PubMed  Google Scholar 

  117. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 5th edn (American Psychiatric Association, 2013).

  118. McAllister, T. W. & Price, T. R. Severe depressive pseudodementia with and without dementia. Am. J. Psychiatry 139, 626–629 (1982).

    Article  CAS  PubMed  Google Scholar 

  119. Collins, S. J. et al. Determinants of diagnostic investigation sensitivities across the clinical spectrum of sporadic Creutzfeldt-Jakob disease. Brain 129, 2278–2287 (2006).

    Article  CAS  PubMed  Google Scholar 

  120. Shrestha, R., Wuerz, T. & Appleby, B. S. Rapidly progressive young-onset dementias: neuropsychiatric aspects. Psychiatr. Clin. North. Am. 38, 221–232 (2015).

    Article  PubMed  Google Scholar 

  121. Irani, S. R. et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann. Neurol. 69, 892–900 (2011).

    Article  PubMed  Google Scholar 

  122. Zetterberg, H. & Bendlin, B. B. Biomarkers for Alzheimer’s disease–preparing for a new era of disease-modifying therapies. Mol. Psychiatry 26, 296–308 (2021).

    Article  PubMed  Google Scholar 

  123. Carswell, C. et al. MRI findings are often missed in the diagnosis of Creutzfeldt-Jakob disease. BMC Neurol. 12, 153 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Boulouis, G. et al. Primary angiitis of the central nervous system: magnetic resonance imaging spectrum of parenchymal, meningeal, and vascular lesions at baseline. Stroke 48, 1248–1255 (2017).

    Article  PubMed  Google Scholar 

  125. Fragoso, D. C. et al. Imaging of Creutzfeldt-Jakob disease: imaging patterns and their differential diagnosis. Radiographics 37, 234–257 (2017).

    Article  PubMed  Google Scholar 

  126. Rudge, P., Hyare, H., Green, A., Collinge, J. & Mead, S. Imaging and CSF analyses effectively distinguish CJD from its mimics. J. Neurol. Neurosurg. Psychiatry 89, 461–466 (2018).

    Article  PubMed  Google Scholar 

  127. Schmidt, C., Plickert, S., Summers, D. & Zerr, I. Pulvinar sign in Wernicke’s encephalopathy. CNS Spectr. 15, 215–218 (2010).

    Article  PubMed  Google Scholar 

  128. Janssen, J. C., Godbolt, A. K., Ioannidis, P., Thompson, E. J. & Rossor, M. N. The prevalence of oligoclonal bands in the CSF of patients with primary neurodegenerative dementia. J. Neurol. 251, 184–188 (2004).

    Article  CAS  PubMed  Google Scholar 

  129. Jacobi, C. et al. Immunoglobulins and virus-specific antibodies in patients with Creutzfeldt-Jakob disease. Acta Neurol. Scand. 111, 185–190 (2005).

    Article  CAS  PubMed  Google Scholar 

  130. Djukic, M. et al. Cerebrospinal fluid abnormalities in meningeosis neoplastica: a retrospective 12-year analysis. Fluids Barriers CNS 14, 7 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  131. Neumann, B. et al. Reactive increase of cerebrospinal fluid white blood cell count after lumbar puncture: fact or fiction? J. Neurol. Sci. 414, 116876 (2020).

    Article  PubMed  Google Scholar 

  132. Malter, M. P., Choi, S. & Fink, G. R. Cerebrospinal fluid findings in non-infectious status epilepticus. Epilepsy Res. 140, 61–65 (2018).

    Article  CAS  PubMed  Google Scholar 

  133. Bajaj, S., Griesdale, D., Agha-Khani, Y. & Moien-Afshari, F. Cerebrospinal fluid pleocytosis not attributable to status epilepticus in first 24 h. Can. J. Neurol. Sci. 49, 210–217 (2022).

    Article  PubMed  Google Scholar 

  134. Dalmau, J. et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 7, 1091–1098 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Jack, C. R. Jr et al. NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 14, 535–562 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Lehmann, S. et al. Diagnosis associated with Tau higher than 1200 pg/mL: insights from the clinical and laboratory practice. Clin. Chem. Acta 495, 451–456 (2019).

    Article  CAS  Google Scholar 

  137. Marquetand, J. et al. Periodic EEG patterns in sporadic Creutzfeld-Jakob-disease can be benzodiazepine-responsive and be difficult to distinguish from non-convulsive status epilepticus. Seizure 53, 47–50 (2017).

    Article  PubMed  Google Scholar 

  138. Sonderen, A. V. et al. Predictive value of electroencephalography in anti-NMDA receptor encephalitis. J. Neurol. Neurosurg. Psychiatry 89, 1101–1106 (2018).

    Article  PubMed  Google Scholar 

  139. Cortelli, P. et al. Pre-symptomatic diagnosis in fatal familial insomnia: serial neurophysiological and 18FDG-PET studies. Brain 29, 668–675 (2006).

    Article  Google Scholar 

  140. Albano, D., Bosio, G., Bertoli, M., Giubbini, R. & Bertagna, F. 18F-FDG PET/CT in primary brain lymphoma. J. Neurooncol 136, 577–583 (2018).

    Article  PubMed  Google Scholar 

  141. Katsanos, A. H. et al. Performance of 18F-FDG, 11C-methionine, and 18F-FET PET for glioma grading: a meta-analysis. Clin. Nucl. Med. 44, 864–869 (2019).

    Article  PubMed  Google Scholar 

  142. Graus, F. et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 15, 391–404 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  143. Riche, M. et al. Complications after frame-based stereotactic brain biopsy: a systematic review. Neurosurg. Rev. 44, 301–307 (2021).

    Article  PubMed  Google Scholar 

  144. Brown, P. et al. Iatrogenic Creutzfeldt-Jakob disease, final assessment. Emerg. Infect. Dis. 18, 901–907 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  145. National Institute for Health and Care Excellence. Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease. Technology appraisal guidance [TA217] (NICE, 2018).

  146. Liu, K. Y. & Howard, R. Can we learn lessons from the FDA’s approval of aducanumab? Nat. Rev. Neurol. 17, 715–722 (2021).

    Article  PubMed  Google Scholar 

  147. Roettger, Y. et al. Immunotherapy in prion disease. Nat. Rev. Neurol. 9, 98–105 (2013).

    Article  CAS  PubMed  Google Scholar 

  148. Raymond, G. J. et al. Antisense oligonucleotides extend survival of prion-infected mice. JCI Insight 5, e131175 (2019).

    Article  Google Scholar 

  149. Abboud, H. et al. Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management. J. Neurol. Neurosurg. Psychiatry 92, 897–907 (2021).

    Article  Google Scholar 

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Acknowledgements

The work of I.Z. is supported by grants from the Robert Koch Institute through funds of the German Federal Ministry of Health (grant no. 1369-341). The authors wish to thank all employees at the German National Reference Center for TSE for performing the Creutzfeldt–Jakob disease surveillance and counselling physicians all over Germany with regard to the differential diagnosis of prion diseases and other rapidly progressive dementias.

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  1. Department of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical Center, Göttingen, Germany

    Peter Hermann & Inga Zerr

  2. German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany

    Inga Zerr

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  1. Peter Hermann
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  2. Inga Zerr
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Hermann, P., Zerr, I. Rapidly progressive dementias — aetiologies, diagnosis and management. Nat Rev Neurol 18, 363–376 (2022). https://doi.org/10.1038/s41582-022-00659-0

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