Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer's disease.
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 (18)F-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.


CONCLUSIONS
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.
Mosconi
Lisa
L
Department of Psychiatry, New York University School of Medicine, New York, New York, USA. lisa.mosconi@med.nyu.edu
Sorbi
Sandro
S
de Leon
Mony J
MJ
Li
Yi
Y
Nacmias
Benedetta
B
Myoung
Paul S
PS
Tsui
Wai
W
Ginestroni
Andrea
A
Bessi
Valentina
V
Fayyazz
Mozghan
M
Caffarra
Paolo
P
Pupi
Alberto
A
D000328:Adult; D017668:Age of Onset; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D001284:Atrophy; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D018450:Disease Progression; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D053764:Presenilin-1 / Q000378:metabolism
D053764:Presenilin-1