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Distinct MRI Atrophy Patterns in Autopsy-Proven Alzheimer's Disease and Frontotemporal Lobar Degeneration

Memory and Aging Center, University of California, San Francisco, California, Departments of Neurology, University of California, San Francisco, California, grabinovici{at}memory.ucsf.edu

W.W. Seeley, MD

Memory and Aging Center, University of California, San Francisco, California, Departments of Neurology, University of California, San Francisco, California

E.J. Kim, MD

Memory and Aging Center, University of California, San Francisco, California, Departments of Neurology, University of California, San Francisco, California

M.L. Gorno-Tempini, MD, PhD

Memory and Aging Center, University of California, San Francisco, California, Departments of Neurology, University of California, San Francisco, California

K. Rascovsky, PhD

Memory and Aging Center, University of California, San Francisco, California

T.A. Pagliaro, BA

Memory and Aging Center, University of California, San Francisco, California

S.C. Allison, BS

Memory and Aging Center, University of California, San Francisco, California

C. Halabi, BS

Memory and Aging Center, University of California, San Francisco, California

J.H. Kramer, PsyD

Memory and Aging Center, University of California, San Francisco, California, Departments of Neurology, University of California, San Francisco, California

J.K. Johnson, PhD

Memory and Aging Center, University of California, San Francisco, California, Departments of Neurology, University of California, San Francisco, California

M.W. Weiner, MD

Department of Radiology, University of California, San Francisoc, California, Magnetic Resonance Imaging Unit San Francisco Veterans Affairs Hospital, San Francisco, California

M.S. Forman, MD, PhD

Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, Institute on Aging Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

J.Q. Trojanowski, MD, PhD

Institute on Aging Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

S.J. DeArmond, MD, PhD

Department of Pathology University of California, San Francisco, California

B.L. Miller, MD

Memory and Aging Center, University of California, San Francisco, California, Departments of Neurology, University of California, San Francisco, California

H.J. Rosen, MD

Memory and Aging Center, University of California, San Francisco, California, Departments of Neurology, University of California, San Francisco, California

To better define the anatomic distinctions between Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), we retrospectively applied voxel-based morphometry to the earliest magnetic resonance imaging scans of autopsy-proven AD (N = 11), FTLD (N = 18), and controls (N = 40). Compared with controls, AD patients showed gray matter reductions in posterior temporoparietal and occipital cortex; FTLD patients showed atrophy in medial prefrontal and medial temporal cortex, insula, hippocampus, and amygdala; and patients with both disorders showed atrophy in dorsolateral and orbital prefrontal cortex and lateral temporal cortex (P_FWE-corr < .05). Compared with FTLD, AD patients had decreased gray matter in posterior parietal and occipital cortex, whereas FTLD patients had selective atrophy in anterior cingulate, frontal insula, subcallosal gyrus, and striatum (P < .001, uncorrected). These findings suggest that AD and FTLD are anatomically distinct, with degeneration of a posterior parietal network in AD and degeneration of a paralimbic fronto-insular-striatal network in FTLD.

Key Words: Alzheimer's disease • frontotemporal lobar degeneration • autopsy • magnetic resonance imaging • voxel-based morphometry

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