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Association Between Clinical Measures and Florbetapir F18 PET Neuroimaging in Mild or Moderate Alzheimer’s Disease Dementia
Michael M. Witte, Ph.D.; Paula Trzepacz, M.D.; Michael Case, M.S.; Peng Yu, Ph.D.; Helen Hochstetler, Pharm.D.; Mitchell Quinlivan, Ph.D.; Karen Sundell, B.S.; David Henley, M.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 2014;26:214-220. doi:10.1176/appi.neuropsych.12120402
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From the Department of Neurosciences, Lilly USA, LLC, Indianapolis, IN (MMW, PT, MC, PY, HH); the Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN (PT, DH); Eli Lilly Australia, West Ryde, Australia (MQ); and Lilly Research Laboratories, Indianapolis, IN (KS, DH).

Send correspondence to Dr. Witte; e-mail: witte_michael_m@lilly.com

Copyright © 2014 by the American Psychiatric Association

Received December 18, 2012; Revised March 21, 2013; Accepted April 22, 2013.


Clinical diagnosis of Alzheimer’s disease (AD) is challenging, with 20% or more of patients misdiagnosed, even by expert clinicians. The authors conducted a retrospective, cross-sectional analysis comparing baseline neuropsychiatric and other clinical characteristics in 199 expert-diagnosed mild and moderate AD dementia patients participating in industry-sponsored clinical trials of an investigational therapy, where 18% lacked florbetapir positron emission tomography (PET) evidence of AD neuropathology. Significant differences were found only for cognition and ApoE ε4 status, but the large degree of score overlap would preclude using these measures to predict AD misdiagnosis. This study highlights the value of amyloid PET when evaluating patients with seemingly typical AD.

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FIGURE 1. Representative FBP-PET Images for Two Subjects

FBP-PET positive scan (top row, SUVR=2.13) and FBP-PET negative scan (bottom row, SUVR=1.01), show a difference of florbetapir uptake between the subjects in lateral temporal, precuneus, lateral frontal, and posterior cingulate cortical regions. Prespecified SUVR threshold of 1.10 (with respect to cerebellum as a reference region) was used to define florbetapir positivity. Transverse (left) and sagittal images (right) are shown at the same level in both subjects.

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TABLE 1.Demographic, Neuropsychiatric, Cognitive, Genomic, and FBP-PET Composite SUVR Values for Patients with Clinically Diagnosed Mild or Moderate Dementia Due to AD, Categorized by FBP-PET Scan Resulta
Table Footer Note

Data are expressed as means±SD (range) or within group n (%) as appropriate and p values are between positive and negative scan groups. AD: Alzheimer’s disease; ADAS-Cog14: Alzheimer’s disease assessment scale – cognitive subscale 14-item version; ADCS-ADL: Alzheimer’s disease cooperative study activities of daily living inventory; CDR-SB: clinical dementia rating – sum of boxes; FBP: 18fluorine-labelled florbetapir; GDS: geriatric depression scale; MMSE: mini mental-state exam; NPI: neuropsychiatric inventory; PET: positron emission tomography; SD: standard deviation; SUVR: standardized uptake value ratio.

Table Footer Note

a FBP-PET scans were categorized as either positive or negative for the presence of abnormal levels of Aβ plaque using a cutoff value of ≥1.1.

Table Footer Note

b Frequencies are analyzed using Fisher’s exact test, means by analysis-of-variance.



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