Alzheimer's disease
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Medscape Today
Andrew Wilner, MD
According to a recent editorial, neurologists should be sharpening their lumbar puncture needles in order to obtain cerebrospinal fluid (CSF) to improve their diagnostic accuracy of Alzheimer's disease.[1] The CSF test employs a 2-component mixture model of beta-amyloid 1-42 (AB1-42) and phosphorylated tau protein 181 (P-tau 181P).[2] Model building and validation relied on data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu/ADNI). The sensitivity of the test was 90% in those with Alzheimer's disease, 72% in those with mild cognitive impairment (MCI), and 36% in controls. The specificity was only 62%.
Commercial assays to diagnose Alzheimer's disease by measurement of CSF beta-amyloid and tau protein have been available for more than a decade. Despite more than 5 million Americans with Alzheimer's disease, and millions more at risk, these CSF tests have yet to be widely adopted by clinical neurologists. At a minimum, there are 2 crucial questions that must be answered before recommending CSF examination as a routine test for Alzheimer's disease.
The first question is does CSF examination improve the accuracy of clinical diagnosis? Clinical diagnostic accuracy of probable Alzheimer's disease according to the standard National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria using autopsy as confirmation produces greater than 85% accuracy.[3] It is not clear how much additional precision is added by a positive CSF test in patients with clinically evident Alzheimer's disease. However, CSF testing may allow more accurate earlier diagnosis.
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