title: FDG and Amyloid PET in Cognitively Normal Individuals at Risk for Late-Onset Alzheimer's Disease.
abstract: Having a parent affected by late-onset Alzheimer's disease (AD) is a major risk factor for cognitively normal (NL) individuals. This study explores the potential of PET with18F-FDG and the amyloid-β(Aβ) tracer11C-Pittsburgh Compound B (PiB) for detection of individual risk in NL adults with AD-parents.
  
  
  METHODS
  FDG- and PiB-PET was performed in 119 young to late-middle aged NL individuals including 80 NL with positive family history of AD (FH+) and 39 NL with negative family history of any dementia (FH-). The FH+ group included 50 subjects with maternal (FHm) and 30 with paternal family history (FHp). Individual FDG and PiB scans were Z scored on a voxel-wise basis relative to modality-specific reference databases using automated procedures and rated as positive or negative (+/-) for AD-typical abnormalities using predefined criteria. To determine the effect of age, the cohort was separated into younger (49 ± 9 y) and older (68 ± 5 y) groups relative to the median age (60 y).
  
  
  RESULTS
  Among individuals of age >60 y, as compared to controls, NL FH+ showed a higher frequency of FDG+ scans vs. FH- (53% vs. 6% p < 0.003), and a trend for PiB+ scans (27% vs. 11%; p = 0.19). This effect was observed for both FHm and FHp groups. Among individuals of age ≤60 y, NL FHm showed a higher frequency of FDG+ scans (29%) compared to FH- (5%, p = 0.04) and a trend compared to FHp (11%) (p = 0.07), while the distribution of PiB+ scans was not different between groups. In both age cohorts, FDG+ scans were more frequent than PiB+ scans among NL FH+, especially FHm (p < 0.03). FDG-PET was a significant predictor of FH+ status. Classification according to PiB status was significantly less successful.
  
  
  CONCLUSIONS
  Automated analysis of FDG- and PiB-PET demonstrates higher rates of abnormalities in at-risk FH+ vs FH- subjects, indicating potentially ongoing early AD-pathology in this population. The frequency of metabolic abnormalities was higher than that of Aβpathology in the younger cohort, suggesting that neuronal dysfunction may precede major aggregated Aβburden in young NL FH+. Longitudinal follow-up is required to determine if the observed abnormalities predict future AD.
authors.affiliation: New York University School of Medicine, New York, USA.
authors.forename: John
authors.initials: J
authors.lastname: Murray
authors.affiliation: New York University School of Medicine, New York, USA.
authors.forename: Wai H
authors.initials: WH
authors.lastname: Tsui
authors.affiliation: New York University School of Medicine, New York, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: New York University School of Medicine, New York, USA.
authors.forename: Pauline
authors.initials: P
authors.lastname: McHugh
authors.affiliation: New York University School of Medicine, New York, USA.
authors.forename: Schantel
authors.initials: S
authors.lastname: Williams
authors.affiliation: New York University School of Medicine, New York, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Cummings
authors.affiliation: New York University School of Medicine, New York, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pirraglia
authors.affiliation: Weill Cornell Medical College, New York, USA.
authors.forename: Lilja
authors.initials: L
authors.lastname: Solnes
authors.affiliation: New York University School of Medicine, New York, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Osorio
authors.affiliation: New York University School of Medicine, New York, USA.
authors.forename: Lidia
authors.initials: L
authors.lastname: Glodzik
authors.affiliation: Weill Cornell Medical College, New York, USA.
authors.forename: Shankar
authors.initials: S
authors.lastname: Vallabhajosula
authors.affiliation: University of Cologne, Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
authors.affiliation: University of Washington, Seattle, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Minoshima
authors.affiliation: New York University School of Medicine, New York, USA.
authors.forename: Mony J
authors.initials: MJ
authors.lastname: de Leon
authors.affiliation: New York University School of Medicine, New York, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Mosconi
keywords: Alzheimer’s Disease; Amyloid Imaging; Early Detection; Glucose Metabolism; Normal Aging; Positron Emission Tomography