Trajectory of clinical symptoms accelerates after 10 years of amyloid

Abstract

AbstractBackgroundUnderstanding the time between amyloid biomarker detection and the onset of cognitive and functional symptoms will be critical in making care planning decisions and determining an optimal time period for potential interventions. Previous studies have suggested that amyloid, as measured with Pittsburg compound B (PiB), can be detected 15‐20 years before symptom onset. However, the designs of these studies do not—on an individual basis—provide an understanding of the duration between amyloid accumulation and symptom onset. Recent research from several groups has suggested that the rate of amyloid accumulation is consistent across individuals, making it possible to estimate the chronicity of amyloid positivity from a single PET scan. In relation to this measure of amyloid chronicity, we examined trajectories of cognitive and functional symptoms, as measured by the Clinical Dementia Rating Scale (CDR).MethodThe sample included 347 study visits from 84 amyloid positive (A+) participants enrolled in the Wisconsin Registry for Alzheimer’s Prevention or the Wisconsin Alzheimer’s Disease Research Center (Table 1). For participant visits that administered the Quick Dementia Rating System (QDRS), the equivalent CDR sum of boxes (CDR‐SB) score was calculated. A mixed effects model with random slope and intercept was used to evaluate the association between chronicity and CDR‐SB (with covariates APOE4 carriage, sex and baseline age). To investigate potential non‐linearity in chronicity’s association with CDR‐SB, a chronicity‐by‐baseline chronicity category (<0, 0‐5, 5‐10, 10‐15, 15‐20 and >20 years) interaction was examined (<0=reference range).ResultSpaghetti plots display the trajectories of CDR‐SB values in relation to amyloid chronicity; shading indicates clinical guidelines for interpreting CDR‐SB (Figure 1). The results of the model indicate that the trajectory of CDR‐SB is significantly greater after 10 years of amyloid chronicity (Table 2 & Figure 2).ConclusionLargely consistent with previous studies, the results indicate that clinical symptoms begin to emerge after 10 years of amyloid positivity. However, symptom severity appeared to vary greatly between 10 – 30 years of amyloid chronicity. Future research will aim to identify other processes that may contribute to decline as well as genetic and modifiable factors that may promote resiliency and delay the onset of clinical symptoms.