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Georges El Fakhri, PhD; Marie Foley Kijewski, ScD; Keith A. Johnson, MD; Grigoriy Syrkin, BS; Ronald J. Killiany, PhD; J. Alex Becker, MS; Robert E. Zimmerman, MSEE; Marilyn S. Albert, PhD

Arch Neurol. 2003;60:1066-1072.

Objective  To identify group differences in the prodromal phase of Alzheimer disease (AD) using quantitative single-photon emission computed tomography (SPECT) perfusion and magnetic resonance imaging (MRI) volume measures within specific volumes of interest.

Setting  Gerontology research unit.

Participants  There were 17 healthy controls, 56 nondemented patients with memory problems who did not develop AD during 3 to 5 years of follow-up (questionables), and 27 nondemented patients with memory problems who developed AD during follow-up (converters).

Methods  A Tc 99m hexamethylpropyleneamine oxime SPECT study and an MRI were performed in each participant at baseline. Mean SPECT activity concentration and MRI volume were estimated within 9 structures: rostral anterior cingulate, caudal anterior cingulate, posterior cingulate, hippocampus, entorhinal cortex, basal forebrain, temporal horn, amygdala, and the banks of the superior temporal sulcus. Data were analyzed using overall and pairwise discriminant analysis, and performance in pairwise group discrimination was measured using correlated receiver operating characteristic curve analysis.

Results  The overall (3-group) discriminant function was significant for SPECT (F test, P<.001) and MRI (F test, P<.0001). For the SPECT analysis, the ranking of structures for discriminating among the 3 groups was, in order of decreasing discriminating power, caudal anterior cingulate, temporal horn, superior temporal sulcus, entorhinal cortex, hippocampus, rostral anterior cingulate, amygdala, basal forebrain, and posterior cingulate. For the MRI analysis, this ranking was entorhinal cortex, superior temporal sulcus, temporal horn, hippocampus, amygdala, caudal anterior cingulate, rostral anterior cingulate, basal forebrain, and posterior cingulate. Combining the 2 modalities yielded significantly better discrimination performance than did either alone. Furthermore, the correlation between SPECT and MRI measures was low.

Conclusion  Measures of structure activity concentration and volume carry independent information; both reveal group differences in prodromal AD.

From the Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (Drs Fakhri and Kijewski and Messrs Syrkin, Becker, and Zimmerman); the Departments of Radiology (Dr Johnson), Neurology (Drs Johnson and Albert), and Psychiatry (Dr Albert), Massachusetts General Hospital and Harvard Medical School, Boston; and the Departments of Anatomy and Neurobiology, Boston University Medical Center (Dr Killiany).

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