Amyloid and tau imaging biomarkers explain cognitive decline from late middle-age

This study investigated differences in retrospective cognitive trajectories between amyloid and tau PET biomarker stratified group in initially cognitively unimpaired participants sampled from the Wisconsin Registry for Alzheimer's Prevention. One hundred an(sixty-seven initially unimpaired individuals (baseline age 59 +/- 6 years; 115 females) were stratified by elevated amyloid-beta and tat status based on C-11-Pittsburgh compound B and F-18-MK-6240 PET imaging. Mixed effects models were used to determine if longitudinal cognitive trajectories based on a composite of cognitive tests including memory and executive function differe(between biomarker groups. Secondary analyses investigated group differences for a variety of cross-sectional health and cognitive tests, and associations between F-18-MK-6240, C-11-PiB, and age. A significant group x age interaction was observed with post bo, comparisons indicating that the group with both elevated amyloid and tau pathophysiology were declining approximately three times faster in retrospective cognition compared to those with just one or no elevated biomarkers. This result was robust agains various thresholds and medial temporal lobe regions defining elevated tau. Participants were relatively healthy and mostly did no differ between biomarker groups in health factors at the beginning or end of study, or most cognitive measures at study entry Analyses investigating association between age, MK-6240 and PiB indicated weak associations between age and F-18-MK-6240 it tangle-associated regions, which were negligible after adjusting for C-11-PiB. Strong associations, particularly in entorhinal cortex hippocampus amygdala, were observed between F-18-MK-6240 :Ind global C-11-PiB in regions associated with Brack neuro-fibrillary tangle stages I-IV. These results suggest that the combination of pathological amyloid and tau is detrimental to cognitive decline in preclinical Alzheimer's disease during, late middle-age. Within the Alzheimer's disease continuum, middle-age health factors likely do not greatly influence preclinical cognitive decline. Future studies in a larger preclinical sample are needed to determine if and to what extent individual contributions of amyloid and tau affect cognitive decline. F-18-MK-6240 shows promise as a sensitive biomarker for detecting neurofibrillary tangles in preclinical Alzheimer's disease.