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Imaging Alzheimer Pathology in Late-Life Depression With PET and Pittsburgh Compound-B

Butters, Meryl A. PhD*; Klunk, William E. MD, PhD* † ‡; Mathis, Chester A. PhD‡ §; Price, Julie C. PhD‡ ∥; Ziolko, Scott K. BS; Hoge, Jessica A. BS; Tsopelas, Nicholas D. MD*; Lopresti, Brian J. BS; Reynolds, Charles F. III MD* † ¶; DeKosky, Steven T. MD, PhD* † ¶; Meltzer, Carolyn C. MD* † ♯ ** ††

Alzheimer Disease & Associated Disorders: July/September 2008 - Volume 22 - Issue 3 - pp 261-268
doi: 10.1097/WAD.0b013e31816c92bf
Original Articles

There is increasing evidence for an empiric link between late-life depression and Alzheimer disease (AD). The neuropathology of AD, previously only confirmed at autopsy, may now be detectable in vivo using selective imaging ligands for β-amyloid. Positron emission tomography (PET) with [11C] 6-OH-BTA-1 [Pittsburgh Compound-B (PiB)] has shown high tracer retention in cortical areas in patients with clinical diagnoses of probable AD and low retention in age-matched controls. We also previously reported variable PiB retention in patients with mild cognitive impairment (MCI). In this study, we used PiB-PET to evaluate whether amyloid is present in elders with treated major depression, many of whom have persistent cognitive impairment. We evaluated 9 subjects with remitted major depression [3M: 6F, mean (SD) age=71.8(5.7) y]. Seven of the 9 depressed subjects also met criteria for the diagnosis of MCI. PiB-PET data from healthy elders [n=8; mean (SD) age=71.5(3.0) y] were used for comparison. PET was acquired with arterial sampling and PiB retention was quantified using magnetic resonance imaging-guided cortical regions and graphical analysis of time-activity data; arterial line failure led to exclusion of 1 depressed subject. The data demonstrated variably elevated PiB retention. PiB retention in the 2 depressed subjects with normal cognitive ability was in the range of nondepressed cognitively normal subjects. PiB retention in 3 of the 6 depressed subjects with MCI fell in the range of subjects with AD. PiB retention in the remaining 3 depressed subjects with cooccurring MCI was variable and generally was intermediate to the other subjects. Our findings are consistent with and supportive of the hypothesis that depression may herald the development of AD in some individuals.

Departments of *Psychiatry





Neuroscience, University of Pittsburgh, Pittsburgh, PA

Departments of Radiology


††Psychiatry and Behavioral Science, Emory University, Atlanta, GA

Supported by PHS grants MH072947, MH67602, MH59945, MH64625, AG25516, AG25204, AG05133, MH43832, MH01210, AG01039, MH71944, MH070729 and MH52247, as well as the John A. Hartford Foundation Center of Excellence in Geriatric Psychiatry and UPMC Endowment in Geriatric Psychiatry.

Dr Reynolds receives research support (pharmaceutical supplies) from Glaxo Smith-Kline, Forest, Pfizer, Lilly, and Bristol Myers Squibb.

Reprints: Meryl A. Butters, PhD, Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O'Hara St., Pittsburgh, PA 15213 (e-mail:

Received for publication January 15, 2007; accepted January 24, 2008

GE Healthcare holds a license agreement with the University of Pittsburgh based on the technology described in this manuscript. Drs Klunk and Mathis are co-inventors of PiB and, as such, have a financial interest in this license agreement. GE Healthcare provided no grant support for this study and had no role in the design or interpretation of results or preparation of this manuscript. All other authors have no conflicts of interest with this work. Drs Butters, Meltzer, Klunk, Mathis, Price, and DeKosky as well as Mr Ziolko had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

© 2008 Lippincott Williams & Wilkins, Inc.