Tau Positron Emission Tomography Better Predicts Cognitive Decline Among Patients With Alzheimer Disease

Memory loss concept
Memory loss, conceptual computer artwork.
The researchers sought to understand the prognostic value of tau positron emission tomography for predicting cognitive decline across the clinical spectrum of Alzheimer disease.

For patients with Alzheimer disease (AD), tau positron emission tomography (PET) was superior at predicting cognitive changes compared with magnetic resonance imaging (MRI) or amyloid PET. These findings were published in JAMA Neurology.

Data (N=1431) collected between 2014 and 2021 for an ongoing study of AD conducted in South Korea, Sweden, and the US were analyzed for this study. Cognitive changes were assessed by tau PET, amyloid PET, and MRI yearly.

Participants had a mean age of 71.2 (SD, 8.8) years, 52.5% were men, 44.7% were positive for apolipoprotein E (APOE) e4, and baseline Mini-Mental State Examination (MMSE) score was 26.7 (SD, 3.9).

The average yearly MMSE score decline was -1.01 (SD, 1.61). Patients with amyloid-b (Ab)-positive AD dementia (n=315) had more rapid yearly decline in MMSE scores (mean, -2.42; SD, 1.87) compared with Ab-positive mild cognitive impairment (MCI; n=271; mean, -1.38; SD, 1.84), Ab-negative MCI (n=172; mean, -0.74; SD, 1.31), Ab-positive cognitively unimpaired (CU; n=253; mean, -0.37; SD, 0.84), or Ab-negative CU (n=420; mean, -0.19; SD, 0.55).

MMSE decline over time was more strongly associated with [18F]flortaucipir uptake as measured by tau PET (R2, 0.35) compared with MRI (R2, 0.24; P <.001). Stratified by AD subtype, the same pattern was observed for both CU groups and the Ab-positive MCI cohort (all P <.001) and the opposite pattern in which MRI outperformed tau PET was observed for Ab-negative MCI and AD dementia groups (both P <.001).

Similar results were observed among a [18F]RO948 replication cohort (R2, tau PET: 0.49 vs MRI: 0.34; P <.001). For the AD dementia replication cohort, tau PET outperformed MRI (R2, 0.26 vs 0.17; P <.001)

In models that predicted MMSE trajectories over time, models including confounders (age, sex, educational attainment, cohort assignment) with tau PET plus MRI outperformed models including cofounders with MRI plus tau PET. Specifically for all Ab-positive individuals (R2, 0.561; b, -0.21 vs R2, 0.546; b, 0.27), the Ab-positive AD dementia cohort (R2, 0.425; b, -0.17 vs R2, 0.414; b, 0.23), Ab-positive MCI group (R2, 0.390; b, -0.26 vs R2, 0.356; b, 0.24), and Ab-positive CU cohort (R2, 0.188; b, -0.18 vs R2, 0.180; b, 0.10).

MMSE decline over time was more strongly associated with [18F]flortaucipir uptake as measured by tau PET (R2, 0.35) compared with amyloid PET (R2, 0.17; P <.001). Stratified by AD subtype the same pattern was observed for the AD dementia, Ab-positive MCI, and both CU cohorts (all P <.001).

Similar results were observed among the [18F]RO948 replication cohort (R2, tau PET: 0.49 vs amyloid PET: 0.25; P <.001).

This study was limited by the short duration of follow-up (mean, 22.7; SD, 9.8 months).

These data indicated that tau PET tracers had superior prognostic utility compared with MRI or amyloid PET for predicting cognitive decline among patients with AD.

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Ossenkoppele R, Smith R, Mattsson-Carlgren N, et al. Accuracy of tau positron emission tomography as a prognostic marker in preclinical and prodromal Alzheimer disease: a head-to-head comparison against amyloid positron emission tomography and magnetic resonance imaging. JAMA Neurol. doi:10.1001/jamaneurol.2021.1858