By Joseph E. Safdieh, MD

Associate Professor of Neurology, Weill Cornell Medical College

Dr. Safdieh reports no financial relationships relevant to this field of study.

Synopsis: The cognitive dysfunction profile in CJD impairs executive function, expressive speech, and parietal function more than memory functions.

Source: Caine D, et al. The cognitive profile of prion disease: A prospective clinical and imaging study: Ann Clin Transl Neurol 2015. DOI 10.1002/acn3.195.

Of the many causes of “rapidly progressive dementia,” Creutzfeldt-Jakob disease (CJD) is the most serious, as there are no established therapies. The disease tends to progress over the course of weeks to months and by the end-stages all patients suffer from a significant dementia. Traditionally, formal neuropsychological testing has been challenging to administer in CJD due to the rapidly progressive nature of the disease. Many patients are too impaired to participate in detailed standardized batteries of neuropsychological tests by the time the diagnosis is being considered. Although many studies focus on the multiple neurologic signs and symptoms of CJD, limited data exist about what, if any, specific pattern of neuropsychological deficits may be present in CJD that might support the diagnosis at an earlier time. Traditionally, the cognitive dysfunction in CJD has been considered to be “generalized” but that finding may be an artifact of testing patients too late in the course of the illness.

In this very detailed study, the authors attempted to perform the first large-scale neuropsychological testing profile of patients with CJD. The study included patients with any form of CJD, including sporadic, inherited, and iatrogenic. All patients were administered a specifically designed short cognitive examination, and those who could participate were administered a full neuropsychological battery. The short cognitive exam included an MMSE and brief tests of visual memory, attention, parietal lobe function, calculation, praxis, language, reading, executive function, perception, and processing speed. The results of the neuropsychological testing was correlated with imaging findings, CSF 14-3-3 protein, as well as demographic, genetic, and clinical variables. Healthy age-matched controls were also included. The authors wanted to determine whether there were any consistent patterns of cognitive dysfunction in CJD and how well they correlated with other objective markers of disease.

A total of 81 patients were tested with the short cognitive exam; of those, 30 were able to complete full neuropsychological testing. Of the 81 patients, 40 had spontaneous CJD, 28 had inherited CJD, eight had iatrogenic CJD, and five had variant CJD. Median age of patients was 55.4 years. The most common presenting symptoms at the time of testing were cognitive dysfunction (89%) and ataxia (78%). Mean MMSE at time of testing was 21.2 for patients and 29.5 for controls. Of the 30 patients able to complete the full neuropsychological profile, 73% had cognitive complaints. Other common symptoms of CJD (in descending order) included anxiety/depression, speech difficulty, personality change, apraxia, myoclonus, extrapyramidal signs, hallucinations, pyramidal signs, sensory disturbances, and diarrhea.


As expected, cognitive function across all domains was demonstrated to be much worse than controls. Patients were impaired on all tasks to some degree. Those patients able to complete the full neuropsychological testing battery demonstrated a general reduction in intelligence as compared to the controls, even in the mildly impaired patients. Analysis of the specific areas of weakness as compared to other domains demonstrated that the major areas of cognitive dysfunction included prominent executive impairment, parietal dysfunction, expressive greater than receptive aphasia, and reduced motor task speed. Of note, this degree of frontal and parietal dysfunction correlated significantly with atrophy in these brain regions on MRI studies. Another notable finding was that nonverbal memory was relatively preserved in patients with CJD as compared to other cognitive domains. Attention was also an area that was relatively spared.

In summary, it is not surprising that patients with CJD have cognitive dysfunction in all domains. However, it is interesting that the dysfunction is more notable in frontal and parietal systems with executive and expressive language dysfunction. This is a pattern that is more similar to the cognitive impairment encountered in other dementia syndromes associated with abnormal movements including cortical basal degeneration, progressive supranuclear palsy, amyotrophic lateral sclerosis, and Lewy Body disease. The pattern is not an amnestic syndrome and would not as easily be confused with an Alzheimer-type cognitive dysfunction. It is also interesting to note that the cognitive impairment in CJD correlated with imaging findings. This study is very useful, as it adds a significant amount of knowledge to the previously poorly defined features of the “dementia” syndrome in the “rapidly progressive dementia” of CJD.