Fig. 2.

Clinical impairment and tau-PET signal increase, whereas hippocampal volumes decrease with PET-Aβ stages. Top row: illustration of the proposed staging system—PiB-PET images exemplifying the three PET stages 0, 1, and 2 (mean image across HABS participants in each stage). The red arrows indicate striatum showing high PET signal in some but not all individuals with high cortical Aβ. Second row: number of participants in each PET-Aβ stage split by clinical diagnostic groups. The blue color indicates individuals with low cortical, low striatal Aβ (stage 0). The green color indicates individuals with high striatal, low cortical Aβ (,1% of participants). The pink color indicates individuals with high cortical, low striatal Aβ (stage 1). The red color indicates individuals with high cortical and high striatal Aβ. Third row: tau-PET signal and adjusted hippocampal volume as a function of PET-Aβ stages. Raw data plot (bars are standard errors); P values are adjusted for demographics and cohort. Last row: longitudinal MMSE by baseline PET-Aβ stages, adjusted for demographics and cohort. PET-Aβ stage 2 individuals have the fastest cognitive decline than any other group. Error bars are 95% confidence intervals. See first two rows of Table 3 for statistics. Abbreviations: Aβ, amyloid β; AD, Alzheimer’s dementia; CN, clinically normal participants; HABS, Harvard Aging Brain study; MCI, mild cognitive impairment.