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Hypometabolism Exceeds Atrophy in Presymptomatic Early-Onset Familial Alzheimer's Disease

Lisa Mosconi1,2, Sandro Sorbi2, Mony J. de Leon1, Yi Li1, Benedetta Nacmias2, Paul S. Myoung1, Wai Tsui1, Andrea Ginestroni2, Valentina Bessi2, Mozghan Fayyazz2, Paolo Caffarra3 and Alberto Pupi2

1 Department of Psychiatry, New York University School of Medicine, New York, New York; 2 Department of Clinical Physiopathology and Neurology, University of Florence, Florence, Italy; and 3 Department of Psychiatry, University of Parma, Parma, Italy


Figure 1
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FIGURE 1.  ROI drawings are displayed on coronal (A and B) and left sagittal (C and D) MR images of a representative FAD subject (FAD-1). (A) Hippocampus (1), entorhinal cortex (2), superior temporal gyrus (3). (B) Ventricles (4), whole brain (5). (C) Posterior cingulate cortex (6). (D) Inferior parietal lobe (7). Left medial temporal lobe is shown magnified in A to highlight hippocampal (1) and entorhinal cortex (2) ROIs.

 

Figure 2
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FIGURE 2.  MRI and 18F-FDG PET scans of 4 subjects. (A) Control subject, male, age = 40 y, MMSE = 30, CDR = 0. (B) FAD, female, age = 35 y, MMSE = 30, CDR = 0 (Table 1, FAD-1). Bilateral hypometabolism of parietal cortex and MTL is evident on PET in absence of atrophy on MRI. Hypometabolism is more severe in left hemisphere. (C) FAD, male, age = 41 y, MMSE = 30, CDR = 0.5 (Table 1, FAD-3). Bilateral hypometabolism of parietal and temporal cortices and of MTL is evident on PET in absence of atrophy on MRI. MTL hypometabolism is more severe in left hemisphere. (D) FAD, female, age = 47 y, MMSE = 25, CDR = 0 (Table 1, FAD-6). Hypometabolism of parietal regions and MTL (bilaterally) and of left temporal lobe is evident on PET. Mild atrophy is present on MRI in parietal/precuneus regions. Within these regions, atrophy correction increased the MRglc measures by 10%, which were still 1 SD below control subjects' mean. Coregistered PET and MRI scans are shown at high (top row), middle (middle row), and low (bottom row) transaxial levels. PET scans are displayed in a blue-to-red color-coded scale, with intensity in each pixel representing radioactive counts per second. 18F-FDG PET images are shown using the same color scale. Areas of regional hypometabolism on PET are indicated by arrows on first slice showing abnormalities.

 

Figure 3
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FIGURE 3.  18F-FDG PET MRglc data for age-, sex-, and education-matched control and FAD subjects. Regional MRglc is averaged across hemispheres. Compared with respective control subjects, all FAD subjects show reduced MRglc values. Two FAD subjects with MMSE scores of 27 of 30 (FAD-5) and 25 of 30 (FAD-6) are marked with a white circle and a white diamond, respectively, and 1 FAD subject with questionable impairment (FAD-3) is marked with a white triangle. Note that these subjects were not driving statistical effects. HIP = hippocampus.

 

Figure 4
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FIGURE 4.  ES were examined for all ROIs, comparing MRI volumes (white) with PET MRglc measures (hatched).

 

Figure 5
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FIGURE 5.  Correlation between PCC MRglc and time to expected age at AD onset in FAD group (r = 0.78, P = 0.005).

 





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