Amyloid-β but not tau accumulation is strongly associated with longitudinal cognitive decline

Abstract

Objective: Alzheimer's disease (AD) pathology is featured by the extracellular accumulation of amyloid-β (Aβ) plaques and intracellular tau neurofibrillary tangles in the brain. We studied whether Aβ and tau accumulation are independently associated with future cognitive decline in the AD continuum. Methods: Data were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) public database. A total of 1272 participants were selected based on the availability of Aβ-PET and CSF tau at baseline and of those 777 participants with follow-up visits. Results: We found that Aβ-PET and CSF tau pathology were related to cognitive decline across the AD clinical spectrum, both as potential predictors for dementia progression. Among them, Aβ-PET (A + T− subjects) is an independent reliable predictor of longitudinal cognitive decline in terms of ADAS-13, ADNI-MEM, and MMSE scores rather than tau pathology (A − T+ subjects), indicating tau accumulation is not closely correlated with future cognitive impairment without being driven by Aβ deposition. Of note, a high percentage of APOE ε4 carriers with Aβ pathology (A+) develop poor memory and learning capacity. Interestingly, this condition is not recurrence in terms of the ADNI-MEM domain when adding APOE ε4 status. Finally, the levels of Aβ-PET SUVR related to glucose hypometabolism more strongly in subjects with A + T− than A − T+ both happen at baseline and longitudinal changes. Conclusions: In conclusion, Aβ-PET alone without tau pathology (A + T−) measure is an independent reliable predictor of longitudinal cognitive decline but may nonetheless forecast different status of dementia progression. However, tau accumulation alone without Aβ pathology background (A − T+) was not enough to be an independent predictor of cognitive worsening.