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@ARTICLE{Farrell:835091,
      author       = {Farrell, Michelle E. and Kennedy, Kristen M. and Rodrigue,
                      Karen M. and Wig, Gagan and Bischof, Gérard N. and Rieck,
                      Jennifer R. and Chen, Xi and Festini, Sara B. and Devous,
                      Michael D. and Park, Denise C.},
      title        = {{A}ssociation of {L}ongitudinal {C}ognitive {D}ecline
                      {W}ith {A}myloid {B}urden in {M}iddle-aged and {O}lder
                      {A}dults},
      journal      = {JAMA neurology},
      volume       = {74},
      number       = {7},
      issn         = {2168-6149},
      address      = {Chicago, Ill.},
      publisher    = {American Medical Association},
      reportid     = {FZJ-2017-04959},
      pages        = {830 - 838},
      year         = {2017},
      abstract     = {Importance Presently, the clinical standard for reporting
                      the results of an amyloid positron emission tomography scan
                      is to assign a dichotomous rating of positive or negative
                      for the presence of amyloid. In a 4-year longitudinal study,
                      we investigated whether using a continuous measure of the
                      magnitude of baseline amyloid burden would provide valuable
                      information about the rate of future cognitive decline over
                      the subsequent 4 years compared with a dichotomous measure
                      in middle-aged and older adults.Objective To examine whether
                      a continuous, dose-response relationship between amyloid
                      burden and cognitive decline was present among middle-aged
                      and older adults.Design, Setting, and Participants This
                      cohort study included 174 participants from the Dallas
                      Lifespan Brain Study who were 40 to 89 years old at the
                      beginning of the study, were cognitively normal at baseline
                      (a Mini-Mental State Examination score of 26 or higher) with
                      no history of neurological or psychiatric disorders, and had
                      completed amyloid imaging ([18F]-florbetapir) at baseline
                      and cognitive assessments at baseline and a 4-year
                      follow-up. Continuous amyloid burden was measured as the
                      mean cortical standardized uptake value ratio (SUVR) at
                      baseline.Main Outcomes and Measures Linear mixed models
                      assessed the effect of increasing baseline amyloid over time
                      (SUVR × time interaction) on episodic memory,
                      reasoning, processing speed, vocabulary, and Mini-Mental
                      State Examination performance. Age, sex, education,
                      apolipoprotein ε4, and the random effect of intercepts were
                      included as covariates.Results The mean (SD) age for all
                      participants (n = 174) was 66.44 (11.74) years, and 65
                      participants $(37\%)$ were men. The primary analyses yielded
                      significant SUVR × time interactions in episodic
                      memory, processing speed, vocabulary, and Mini-Mental State
                      Examination performance, but not in reasoning performance.
                      Higher baseline SUVR projected greater cognitive decline
                      over 4 years. When controlling for variance related to a
                      dichotomized positive/negative classification, most effects
                      on cognition remained. Dichotomized amyloid status alone
                      yielded fewer significant effects of amyloid on cognitive
                      decline than continuous SUVR. Among amyloid-positive
                      participants, increasing baseline SUVR predicted an
                      increasing decline in episodic memory, but other effects on
                      cognition were more limited. Finally, higher baseline
                      amyloid burden among middle-aged adults was related to
                      changes in vocabulary, with the effect driven by 3
                      apolipoprotein ε4 homozygotes.Conclusions and Relevance
                      These results suggest that the magnitude of amyloid burden
                      at baseline is associated with the rate of cognitive decline
                      over 4 years and potentially provides important information
                      about the rate of future cognitive decline that is not
                      available from a dichotomous positive/negative
                      categorization.},
      cin          = {INM-3},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-3-20090406},
      pnm          = {572 - (Dys-)function and Plasticity (POF3-572)},
      pid          = {G:(DE-HGF)POF3-572},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000405077100015},
      pubmed       = {pmid:28558099},
      doi          = {10.1001/jamaneurol.2017.0892},
      url          = {https://juser.fz-juelich.de/record/835091},
}