Plaque and tangle imaging and cognition in normal aging and Alzheimer's disease.
Amyloid plaques and tau neurofibrillary tangles, the pathological hallmarks of Alzheimer's disease (AD), begin accumulating in the healthy human brain decades before clinical dementia symptoms can be detected. There is great interest in how this pathology spreads in the living brain and its association with cognitive deterioration. Using MRI-derived cortical surface models and four-dimensional animation techniques, we related cognitive ability to positron emission tomography (PET) signal from 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([(18)F]FDDNP), a molecular imaging probe for plaques and tangles. We examined this relationship at each cortical surface point in 23 older adults (10 cognitively intact, 6 with amnestic mild cognitive impairment, 7 with AD). [(18)F]FDDNP-PET signal was highly correlated with cognitive performance, even in cognitively intact subjects. Animations of [(18)F]FDDNP signal growth with decreased cognition across all subjects (http://www.loni.ucla.edu/ approximately thompson/FDDNP/video.html) mirrored the classic Braak and Braak trajectory in lateral temporal, parietal, and frontal cortices. Regions in which cognitive performance was significantly correlated with [(18)F]FDDNP signal include those that deteriorate earliest in AD, suggesting the potential utility of [(18)F]FDDNP for early diagnosis.
Braskie
Meredith N
MN
Helen Wills Neuroscience Institute, University of California Berkeley, CA 94720, USA.
Klunder
Andrea D
AD
Hayashi
Kiralee M
KM
Protas
Hillary
H
Kepe
Vladimir
V
Miller
Karen J
KJ
Huang
S-C
SC
Barrio
Jorge R
JR
Ercoli
Linda M
LM
Siddarth
Prabha
P
Satyamurthy
Nagichettiar
N
Liu
Jie
J
Toga
Arthur W
AW
Bookheimer
Susan Y
SY
Small
Gary W
GW
Thompson
Paul M
PM
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D053327:Apolipoprotein E4 / Q000235:genetics; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000473:pathology; D003071:Cognition; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000000981:diagnostic imaging* / Q000473:pathology; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000473:pathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
D053327:Apolipoprotein E4; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals