Accelerated cortical atrophy in cognitively normal elderly with high β-amyloid deposition.
OBJECTIVE
Given the recent and growing interest in the concepts of prodromal and presymptomatic Alzheimer disease, it is crucial to determine whether the presence of β-amyloid (Aβ) in the brain of asymptomatic elderly individuals is a pathologic condition associated with accelerated neuronal and synaptic loss. The aim of the present study was to assess whether Aβ influences the rate of atrophy in cognitively normal elderly individuals.


METHODS
Seventy-four healthy elderly individuals underwent an MRI scan and a 11C-Pittsburgh compound B (PiB) PET scan at baseline and a second MRI scan 18 months later. Voxel-wise analyses were performed using maps of annual rate of atrophy generated from the serial MRI scans, including comparison between individuals with high vs low neocortical PiB and correlation with baseline neocortical PiB.


RESULTS
The rate of atrophy was significantly higher in the normal elderly individuals with high PiB compared with those with low PiB and was significantly correlated with baseline neocortical PiB, with the highest significance in the temporal neocortex and the posterior cingulate cortex.


CONCLUSIONS
Our findings show that the presence of Aβ in the brain, known to occur in about one-third of asymptomatic elderly individuals, is actually a pathologic state associated with accelerated atrophy. They also suggest that therapy aimed to reduce the neurodegenerative process should be commenced in presymptomatic individuals with high PiB.
Department of Nuclear Medicine, Austin Health, Melbourne, Australia. chetelat@cyceron.fr
G
G
Chételat
V L
VL
Villemagne
N
N
Villain
G
G
Jones
K A
KA
Ellis
D
D
Ames
R N
RN
Martins
C L
CL
Masters
C C
CC
Rowe
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001284:Atrophy; D001931:Brain Mapping; D002531:Cerebellum / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D003071:Cognition / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000473:pathology / Q000523:psychology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D019579:Neocortex / Q000473:pathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D013844:Thiazoles