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

To examine the feasibility of using cross-sectional PET to identify cognitive decliners among β-amyloid (Aβ)-negative cognitively normal (CN) elderly adults.

We determined the highest Aβ-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 Aβ-affected region, and Aβ positivity in this region was defined as above the lowest boundary of BANKSSTS standardized uptake value ratio of Aβ+ (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.

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.

Nominally Aβ- CN individuals with high Aβ in BANKSSTS are at increased risk of cognitive decline, probably showing an earlier stage of Aβ deposition. Our findings may help elucidate the association between brain Aβ accumulation and cognition in Aβ- CN cohorts.

This study provides Class II evidence that in elderly CN individuals those with high PET-identified superior temporal sulcus Aβ burden have an increased risk of cognitive decline.