title: Shapes of the trajectories of 5 major biomarkers of Alzheimer disease.
abstract: OBJECTIVE
  To characterize the shape of the trajectories of Alzheimer disease biomarkers as a function of Mini-Mental State Examination (MMSE) score.
  
  
  METHODS
  Longitudinal registries from the Mayo Clinic and the Alzheimer's Disease Neuroimaging Initiative.
  
  
  METHODS
  Two different samples (n = 343 and n = 598) were created that spanned the cognitive spectrum from normal to Alzheimer disease dementia. Subgroup analyses were performed in members of both cohorts (n = 243 and n = 328) who were amyloid positive at baseline.
  
  
  METHODS
  The shape of biomarker trajectories as a function of MMSE score, adjusted for age, was modeled and described as baseline (cross-sectional) and within-subject longitudinal effects. Biomarkers evaluated were cerebrospinal fluid (CSF) Aβ42 and tau levels, amyloid and fluorodeoxyglucose positron emission tomography imaging, and structural magnetic resonance imaging.
  
  
  RESULTS
  Baseline biomarker values generally worsened (ie, nonzero slope) with lower baseline MMSE score. Baseline hippocampal volume, amyloid positron emission tomography, and fluorodeoxyglucose positron emission tomography values plateaued (ie, nonlinear slope) with lower MMSE score in 1 or more analyses. Longitudinally, within-subject rates of biomarker change were associated with worsening MMSE score. Nonconstant within-subject rates (deceleration) of biomarker change were found in only 1 model.
  
  
  CONCLUSIONS
  Biomarker trajectory shapes by MMSE score were complex and were affected by interactions with age and APOE status. Nonlinearity was found in several baseline effects models. Nonconstant within-subject rates of biomarker change were found in only 1 model, likely owing to limited within-subject longitudinal follow-up. Creating reliable models that describe the full trajectories of Alzheimer disease biomarkers will require significant additional longitudinal data in individual participants.
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota, USA. jack.clifford@mayo.edu
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Vemuri
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Wiste
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Weigand
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Lesnick
authors.forename: Val
authors.initials: V
authors.lastname: Lowe
authors.forename: Kejal
authors.initials: K
authors.lastname: Kantarci
authors.forename: Matt A
authors.initials: MA
authors.lastname: Bernstein
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Gunter
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000235:genetics; D000682:Amyloid / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000453:epidemiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D007118:Immunoassay; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D017711:Nonlinear Dynamics; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D049268:Positron-Emission Tomography; D013844:Thiazoles; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D015415:Biomarkers; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D019788:Fluorodeoxyglucose F18