Can MRI screen for CSF biomarkers in neurodegenerative disease?

Imaging advances are always potentially interesting but the immediate risk might be more dementia diagnoses delivered without much regard to functional context, and without proper support and follow-up.

Can MRI screen for CSF biomarkers in neurodegenerative disease?

  1. Corey T. McMillan, PhD,
  2. Brian Avants, PhD,
  3. David J. Irwin, MD,
  4. Jon B. Toledo, MD,
  5. David A. Wolk, MD,
  6. Vivianna M. Van Deerlin, MD, PhD,
  7. Leslie M. Shaw, PhD,
  8. John Q. Trojanoswki, MD, PhD and
  9. Murray Grossman, MD, EdD

+ Author Affiliations

  1. From the Department of Neurology (C.T.M., D.J.I., D.A.W., M.G.), Center for Neurodegenerative Disease Research (D.J.I., J.B.T., V.M.V.D., L.M.S., J.Q.T.), Department of Radiology (B.A.), Penn Memory Center (D.A.W.), and Department of Pathology & Laboratory Medicine (V.M.V.D., L.M.S., J.Q.T.), University of Pennsylvania, Philadelphia.
  1. Correspondence to Dr. McMillan:

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Objective: Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) may have overlapping clinical presentations despite distinct underlying neuropathologies, thus making in vivo diagnosis challenging. In this study, we evaluate the utility of MRI as a noninvasive screening procedure for the differential diagnosis of AD and FTLD.

Methods: We recruited 185 patients with a clinically diagnosed neurodegenerative disease consistent with AD or FTLD who had a lumbar puncture and a volumetric MRI. A subset of 32 patients had genetic or autopsy-confirmed AD or FTLD. We used singular value decomposition to decompose MRI volumes and linear regression and cross-validation to predict CSF total tau (tt) and ?-amyloid (A?1-42) ratio (tt/A?) in patients with AD and patients with FTLD. We then evaluated accuracy of MRI-based predicted tt/A? using 4 converging sources including neuroanatomic visualization and categorization of a subset of patients with genetic or autopsy-confirmed AD or FTLD.

Results: Regression analyses showed that MRI-predicted tt/A? is highly related to actual CSF tt/A?. In each group, both predicted and actual CSF tt/A? have extensively overlapping neuroanatomic correlates: low tt/A? consistent with FTLD is related to ventromedial prefrontal regions while high tt/A? consistent with AD is related to posterior cortical regions. MRI-predicted tt/A? is 75% accurate at identifying underlying diagnosis in patients with known pathology and in clinically diagnosed patients with known CSF tt/A? levels.

Conclusion: MRI may serve as a noninvasive procedure that can screen for AD and FTLD pathology as a surrogate for CSF biomarkers.


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  • Editorial, page 126

  • Supplemental data at

  • Received May 17, 2012.
  • Accepted August 14, 2012.

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