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

ABSTRACT

OBJECTIVE: To examine the feasibility of using cross-sectional PET to identify cognitive decliners among ß-amyloid (Aß)-negative cognitively normal (CN) elderly adults. METHODS: We determined the highest Aß-affected region by ranking baseline and accumulation rates of florbetapir-PET regions in 355 CN elderly adults using 18F-florbetapir-PET from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The banks of the superior temporal sulcus (BANKSSTS) were found as the highest Aß-affected region, and Aß positivity in this region was defined as above the lowest boundary of BANKSSTS standardized uptake value ratio of Aß+ (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 18F-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 Aß- CN individuals with high Aß in BANKSSTS are at increased risk of cognitive decline, probably showing an earlier stage of Aß deposition. Our findings may help elucidate the association between brain Aß accumulation and cognition in Aß- CN cohorts. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that in elderly CN individuals those with high PET-identified superior temporal sulcus Aß burden have an increased risk of cognitive decline.