Detecting earlier stages of amyloid deposition using PET in cognitively normal elderly adults

Objective To examine the feasibility of using cross-sectional PET to identify cognitive decliners among beta-amyloid (A beta)-negative cognitively normal (CN) elderly adults. Methods We determined the highest A beta-affected region by ranking baseline and accumulation rates of florbetapir-PET regions in 355 CN elderly adults using F-18-florbetapir-PET from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The banks of the superior temporal sulcus (BANKSSTS) were found as the highest A beta-affected region, and A beta positivity in this region was defined as above the lowest boundary of BANKSSTS standardized uptake value ratio of A beta+ (ADNI-defined COMPOSITE region) CN individuals. The entire CN cohort was divided as follows: stage 0, BANKSSTS-COMPOSITE-; stage 1, BANKSSTS+COMPOSITE-; and stage 2, BANKSSTS+COMPOSITE+. Linear mixed-effect (LME) models investigated subsequent longitudinal cognitive change, and F-18-flortaucipir (FTP)-PET was measured 4.8 +/- 1.6 years later to track tau deposition. Results LME analysis revealed that individuals in stage 1 (n = 64) and stage 2 (n = 99) showed 2.5 (p < 0.05) and 4.8 (p < 0.001) times faster memory decline, respectively, than those in stage 0 (n = 191) over >4 years of mean follow-up. Compared to stage 0, both stage 1 (p < 0.05) and stage 2 (p < 0.001) predicted higher FTP in entorhinal cortex. Conclusions Nominally A beta- CN individuals with high A beta in BANKSSTS are at increased risk of cognitive decline, probably showing an earlier stage of A beta deposition. Our findings may help elucidate the association between brain A beta accumulation and cognition in A beta- CN cohorts. Classification of evidence This study provides Class II evidence that in elderly CN individuals those with high PET-identified superior temporal sulcus A beta burden have an increased risk of cognitive decline.