Predicting Symptom Onset in Sporadic Alzheimer Disease With Amyloid PET.

OBJECTIVE To predict when cognitively normal individuals with brain amyloidosis will develop symptoms of Alzheimer disease (AD). METHODS Brain amyloid burden was measured by amyloid PET with Pittsburgh compound B. The mean cortical standardized uptake value ratio (SUVR) was transformed into a timescale using longitudinal data. RESULTS Amyloid accumulation was evaluated in 236 individuals who underwent more than one amyloid PET scan. The average age was 66.5 ± 9.2 years and twelve individuals (5%) had cognitive impairment at their baseline amyloid PET scan. A tipping point in amyloid accumulation was identified at a low level of amyloid burden (SUVR 1.2), after which nearly all individuals accumulated amyloid at a relatively consistent rate until reaching a high level of amyloid burden (SUVR 3.0). The average time between levels of amyloid burden was used to estimate the age at which an individual reached SUVR 1.2. Longitudinal clinical diagnoses for 180 individuals were aligned by the estimated age at SUVR 1.2. In the twenty-two individuals who progressed from cognitively normal to a typical AD dementia syndrome, the estimated age at which an individual reached SUVR 1.2 predicted the age at symptom onset (R2=0.54, p<0.0001, root mean square error (RMSE) 4.5 years); the model was more accurate after exclusion of three likely misdiagnoses (R2=0.84, p<0.0001, RMSE of 2.8 years). CONCLUSIONS The age of symptom onset in sporadic AD is strongly correlated with the age that an individual reaches a tipping point in amyloid accumulation.