title: Plaque and tangle imaging and cognition in normal aging and Alzheimer's disease.
abstract: 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.
authors.affiliation: Helen Wills Neuroscience Institute, University of California Berkeley, CA 94720, USA.
authors.forename: Meredith N
authors.initials: MN
authors.lastname: Braskie
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Klunder
authors.forename: Kiralee M
authors.initials: KM
authors.lastname: Hayashi
authors.forename: Hillary
authors.initials: H
authors.lastname: Protas
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kepe
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Miller
authors.forename: S-C
authors.initials: SC
authors.lastname: Huang
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Barrio
authors.forename: Linda M
authors.initials: LM
authors.lastname: Ercoli
authors.forename: Prabha
authors.initials: P
authors.lastname: Siddarth
authors.forename: Nagichettiar
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Toga
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Bookheimer
authors.forename: Gary W
authors.initials: GW
authors.lastname: Small
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
mesh_terms: 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
chemical_list: D053327:Apolipoprotein E4; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals