Clinicians should have an understanding of a lumbar puncture is indicated in the differential diagnosis of dementia and delirium. In most cases, this procedure is not commonly performed in outpatient practice for the differential diagnosis of dementia. However, in patients who have acute or subacute onset or a very rapid decline—such as in suspected Creutzfeldt-Jakob disease (CJD)—cerebrospinal fluid (CSF) 14-3-3, and tau proteins can be diagnostic for at least sporadic CJD. Practice parameters from the American Academy of Neurology (AAN) suggest performing a spinal tap on patients ≤55 years of age. However, that recommendation may not always be beneficial, particularly in a patient who has a prominent family history of either Alzheimer’s disease (AD) or frontotemporal dementia. Per the AAN practice parameter, lumbar puncture for CSF analysis is indicated in the diagnosis of central nervous system (CNS) infection, carcinomatous meningitis, or CNS vasculitis.

Beyond the clinically indicated lumbar puncture, there is utility of CSF biomarkers, including CSF Aβ42, total tau, and phospho-tau, which are the best studied. These biomarkers may be useful for cases involving atypical presentations of dementia, eg, when it is difficult to determine if the patient has AD versus frontotemporal dementia. They may be most useful for cases in which there is an atypical presentation of the fluorodeoxyglucose PET image or PET image features of both AD and frontotemporal dementia.