This patient most likely has Creutzfeldt-Jakob disease (CJD), a dementing illness that occurs subacutely over weeks to months and is classified as a rapidly progressive dementia. This patient has the hallmark neuroradiologic finding of sporadic CJD, namely, hyperintensities on diffusion-weighted imaging (DWI), in this instance involving the basal ganglia and insular and left parietal cortices. DWI hyperintensities also can occur in the cerebral cortex (as cortical ribboning) and thalamus in CJD. DWI is highly sensitive and specific for the diagnosis of sporadic CJD.

Alzheimer disease can present as a rapidly progressive dementia, but not commonly. The MRI findings seen in this patient are not consistent with Alzheimer disease, in which the MRI is typically normal or shows focal atrophy involving the temporal and/or parietal lobes.

Rapidly progressive dementias are relatively uncommon and are more likely to be due to treatable, reversible causes than are the more typical dementing conditions that develop over years. Herpes simplex virus 1 (HSV-1) encephalitis typically results in an acute neurologic decline occurring over days to 1 week rather than months as with this patient. Fever, focal neurologic findings, and focal seizures are common. T2 hyperintensities (and occasionally DWI hyperintensities), with a predilection for the temporal lobes, are strongly suggestive of HSV-1 encephalitis, rather than the DWI abnormalities seen in this patient.

Vascular neurocognitive disorder is characterized by cognitive impairment occurring after a clinical stroke or in the presence of neuroimaging findings of cerebrovascular disease. The prevalence of poststroke dementia is approximately 30%. This patient has neither the history nor focal neurologic signs (such as hemiparesis, facial droop, or dysarthria) to suggest that a clinical stroke has occurred. Although DWI is very sensitive in the detection of early ischemic infarction, the DWI abnormalities seen in this patient do not follow vascular territories and are instead classic for sporadic CJD.