Shapes of the Trajectories of 5 Major Biomarkers of Alzheimer Disease
JAMA Neurology, 04/02/2012

Jack CR et al. – Biomarker trajectory shapes by Mini–Mental State Examination (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.

• 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.
• 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) A β42 and tau levels, amyloid and fluorodeoxyglucose positron emission tomography imaging, and structural magnetic resonance imaging.

• 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.