636 Neurocognitive Disorders
Risk Factors and Prognosis
Environmental. Cross-species transmission  of prion infections, with agents that are
closely related to the human form, has been demonstrated (e.g., the outbreak of bovine
spongiform encephalopathy inducing variant CJD in the United Kingdom during the mid-
1990s). Transmission by corneal transplantation and by human growth factor injection has
been documented, and anecdotal cases of tran smission to health care workers have been
reported.
Genetic and physiological. There is a genetic component in up to 15% of cases, associ-
ated with an autosoma l dominant mutation.
Diagnostic Markers
Prion disease can be definitively confirmed only by biopsy or at autopsy. Although there are
no distinctive findings on cerebrospinal fluid analysis across the prion diseases, reliable bio-
markers are being developed and include 14-3-3 protein (particularly for sporadic CJD) as
well as tau protein. Magnetic resonance brain imaging is currently considered the most sen-
sitive diagnostic test when DWI is performed, with the most common finding being multi-
focal gray matter hyperintensities in subcortical and cortical regions. In some individuals,
the electroencephalogram reve als periodic sharp, often triphasic and synchronous dis-
charges at a rate of 0.5–2 Hz at some point during the course of the disorder. 
Differential Diagnosis
Other major neurocognitive disorders. Major NCD due to prion disease may appear
similar in its course to other NCDs, but prio n diseases are typically distinguished by their
rapid progression and prominent cerebellar and motor symptoms.
Major or Mild Neurocognitive Disorder
Due to Parkinson’s Disease
Diagnostic Criteria  
A. The criteria are met for major or mild neurocognitive disorder.