An MRI method to predict the ratio of total tau (tt) to beta amyloid (AB) may provide a screening tool that could help discriminate between Alzheimer’s disease (AD) and frontotemporal lobar degeneration, according to a study published online Dec. 26, 2012, in Neurology. The findings could allow some patients to bypass the traditional lumbar puncture required to assess tt/AB and differentiate the disorders.
AD and frontotemporal lobar degeneration share common clinical features, so diagnosis based on clinical symptoms is unreliable. Although cerebrospinal fluid tt/AB provides a sensitive and specific means of differentiating the disorders, patients often perceive a lumbar puncture as invasive. The issue is magnified in the clinical trial setting, where patients may require serial assessments of the tt/AB biomarker.
Corey T. McMillan, PhD, from the department of neurology at University of Pennsylvania in Philadelphia, and colleagues devised an MRI-based algorithm to predict tt/AB values and tested the approach with 185 patients diagnosed with a neurodegenerative disease.
Patients enrolled in the study had a cerebrospinal fluid profile consistent with AD or frontotemporal lobar degeneration, and a validation cohort of 32 patients had a genetic mutation consistent with AD or frontotemporal lobar degeneration or an autopsy to confirm the diagnosis.
After deriving the predicted tt/AB values using the MRI method, McMillan and colleagues compared the predicted values with the actual tt/AB ratio for all patients. They reported 75 percent classification accuracy based on MRI-predicted tt/AB relative to actual tt/AB.
“This study established empirical evidence that an MRI-based technique can predict a single, biologically valid level of cerebrospinal fluid tt/AB,” wrote McMillan and colleagues.
They detailed several advantages to the approach. It could decrease the number of patients referred for lumbar puncture; only borderline cases might be referred for the more invasive lumbar puncture to gather actual tt/AB. MRI is less expensive and more available than PET imaging, and can be more easily repeated than a PET study or lumbar puncture. The method also may reduce power demands of clinical studies by providing a candidate marker to monitor in trials. Finally, the method allows researchers to monitor the effects of therapies that target tau or beta amyloid.
McMillan and colleagues called for additional studies to build understanding of the role of cerebrospinal fluid analytes and cortical atrophy. In an accompanying editorial, Christian Habeck, PhD, from the department of neurology at Columbia University in New York City, and Jennifer L. Whitwell, PhD, from Mayo Clinic in Rochester, Minn., added, “An empirical test of the tt/AB prediction from brain data in an independent sample will be an important additional step before this method could be confidently applied to other cohorts.”
Habeck and Whitwell also noted that McMillan et al leveraged existing software tools to develop the MRI algorithm, and wrote other clinician-scientists could use similar software tools. “The initial investment of familiarization with such tools will be well worth the payoff,” they wrote.