Trajectory of clinical symptoms in relation to amyloid chronicity

Abstract

Introduction: While it is generally appreciated that amyloid precedes symptomatic Alzheimer's disease (AD) by decades, a greater understanding of this timeline may increase prognostic accuracy, planning, and care of persons who are on the AD continuum.

Methods: We examined trajectories of Clinical Dementia Rating-Sum of Boxes (CDR-SB) relative to estimated years of amyloid positivity (A+) in n = 123 participants who were all A+ based on [C-11]Pittsburgh compound B positron emission tomography.

Results: The average amyloid chronicity at CDR-SB of 2.5 was 20.1 years. The average trajectory of CDR-SB accelerated after 10 years of elevated amyloid and varied greatly between 10 and 30 years. Exploratory analyses suggested that older age and higher volume of white matter hyperintensities shortened the interval between amyloid onset and cognitive impairment.

Discussion: The recontextualization of amyloid burden into the time domain will facilitate studies of disease progression, the influence of co-pathology, and factors that hasten or slow cognitive impairment.

Keywords: Alzheimer's disease; amyloid imaging; biomarkers; dementia; white matter hyperintensities.

FIGURE 1

Spaghetti plots display individual trajectories of Clinical Dementia Rating (CDR) Sum of Boxes in relation to amyloid chronicity years. The blue trend line uses a locally estimated scatterplot smoothing function with the standard error shaded in gray. The colored shading displays the range of clinical severity guidelines

FIGURE 2

Split histograms display the distribution of white matter hyperintensity (WMH) volumes (mL) among those who are less susceptible to amyloid chronicity (blue) and those who are more susceptible to amyloid chronicity (red)