title: Prediction of cognitive decline by positron emission tomography of brain amyloid and tau.
abstract: OBJECTIVE
  To determine whether 2-(1-{6-[(2-fluorine 18-labeled fluoroethyl)methylamino]-2-napthyl}ethylidene) malononitrile ([(18)F]FDDNP) brain regional values in individuals without dementia predict and correlate with future cognitive change.
  
  
  METHODS
  Two-year, longitudinal follow-up study.
  
  
  METHODS
  A university research institute.
  
  
  METHODS
  Volunteer sample of 43 middle-aged and older persons (median age, 64 years), including 21 with mild cognitive impairment (MCI) and 22 with normal aging.
  
  
  METHODS
  Longitudinal [(18)F]FDDNP positron emission tomography (PET) binding values in the medial and lateral temporal, posterior cingulate, parietal, frontal, and global (mean) regions of interest; neuropsychological test battery measuring 5 cognitive domains, including memory, language, attention (and information-processing speed), executive functioning, and visuospatial ability.
  
  
  RESULTS
  For the entire study group (MCI and normal aging), increases in frontal, posterior cingulate, and global binding at follow-up correlated with progression of memory decline (r = -0.32 to -0.37, P = .03 to .01) after 2 years. Moreover, higher baseline [(18)F]FDDNP binding was associated with future decline in most cognitive domains, including language, attention, executive, and visuospatial abilities (r = -0.31 to -0.56, P = .05 to .002). For the MCI group, frontal and parietal [(18)F]FDDNP binding yielded the greatest diagnostic accuracy in identifying converters to Alzheimer disease vs nonconverters after 2 years, with an area under the receiver operating characteristic curve of 0.88 (95% CI, 0.72-1.00) compared with 0.68 (95% CI, 0.45-0.91) for medial temporal binding.
  
  
  CONCLUSIONS
  [(18)F]FDDNP PET regional binding patterns are consistent with known neuropathologic patterns of plaque and tangle brain accumulation, spreading from the medial temporal to other neocortical regions as disease progresses. Because binding patterns predict future cognitive decline and increase over time along with clinical decline, [(18)F]FDDNP PET scanning may have practical utility in identifying people at risk for future cognitive decline and in tracking the effectiveness of novel interventions designed to prevent or delay neurodegeneration and cognitive decline.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA 90024, USA. gsmall@mednet.ucla.edu
authors.forename: Gary W
authors.initials: GW
authors.lastname: Small
authors.forename: Prabha
authors.initials: P
authors.lastname: Siddarth
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kepe
authors.forename: Linda M
authors.initials: LM
authors.lastname: Ercoli
authors.forename: Alison C
authors.initials: AC
authors.lastname: Burggren
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Bookheimer
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Miller
authors.forename: Jeanne
authors.initials: J
authors.lastname: Kim
authors.forename: Helen
authors.initials: H
authors.lastname: Lavretsky
authors.forename: S-C
authors.initials: SC
authors.lastname: Huang
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Barrio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058227:Amyloidogenic Proteins / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology*; D003072:Cognition Disorders / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007211:Indoles; D007546:Isoquinolines; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C109176:12-formyl-5,6-dihydro-3,9-dihydroxy-6-propylindolo(2,1-a)isoquinoline; D058227:Amyloidogenic Proteins; D007211:Indoles; D007546:Isoquinolines; D019275:Radiopharmaceuticals; D016875:tau Proteins