RT Journal Article SR Electronic T1 Hypometabolism Exceeds Atrophy in Presymptomatic Early-Onset Familial Alzheimer's Disease JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1778 OP 1786 VO 47 IS 11 A1 Lisa Mosconi A1 Sandro Sorbi A1 Mony J. de Leon A1 Yi Li A1 Benedetta Nacmias A1 Paul S. Myoung A1 Wai Tsui A1 Andrea Ginestroni A1 Valentina Bessi A1 Mozghan Fayyazz A1 Paolo Caffarra A1 Alberto Pupi YR 2006 UL http://jnm.snmjournals.org/content/47/11/1778.abstract AB The aim of the present study is to compare brain atrophy with hypometabolism as preclinical markers of Alzheimer's disease (AD) by studying presymptomatic individuals from families with known early-onset autosomal dominant AD (FAD) carrying mutations in the Presenilin 1 gene. Methods: Seven asymptomatic at-risk FAD individuals (age, 35–49 y; 4 women; education ≥ 12 y) and 7 matched healthy control subjects received complete clinical, neuropsychologic, MRI, and 18F-FDG PET examinations. Regions of interest (ROIs: whole brain [WB], hippocampus [Hip], entorhinal cortex [EC], posterior cingulate cortex [PCC], inferior parietal lobule [IPL], and superior temporal gyrus (STG]) were drawn on the MRI scans of all subjects and used to measure volumes on MRI and glucose metabolism (MRglc) from the MRI-coregistered, atrophy-corrected PET scans. Results: Compared with controls and after correcting for head size, MRI volume reductions in FAD subjects were restricted to the IPL (18%, P < 0.02). After atrophy correction and adjusting for pons MRglc, PET MRglc reductions were found in all FAD subjects compared with controls in the WB (13%), bilaterally in the IPL (17%) and in the STG (12%), and in the left EC (21%), PCC (20%), and Hip (12%) (P values < 0.05). PET MRglc measurements were consistently less variable than MRI measures, yielding significantly larger effect sizes in separating FAD from controls. Conclusion: Presymptomatic FAD individuals show widespread MRglc reductions consistent with the typical AD PET pattern in the relative absence of structural brain atrophy. These data further suggest that PET MRglc measures may serve as biomarkers for the preclinical diagnosis of AD.