Tau-PET: Best predictor for dementia progression in MCI patients

Tau-PET outperforms amyloid-β (Aß) PET and MRI as the best neuroimaging marker for predicting progression to dementia in patients with mild cognitive impairment (MCI), a cohort study has shown.

Aß on PET and atrophy on MRI are neuroimaging markers widely used in the clinical setting to predict progression to dementia. However, MRI shows low sensitivity for predicting subtle cognitive changes, while many individuals with amyloid positivity never develop cognitive impairment during their lifetime. Tau protein may be a key driver of Alzheimer’s disease (AD), and its deposition in the brain can also be captured through PET scans. [JAMA Neurol 2024;81:845-856; Brain Res Bull 2022:190:204-217]

To evaluate the prognostic performance of tau PET in predicting clinical progression from MCI to dementia, the researchers included 448 patients with MCI in a multicentre cohort study with a mean follow-up of 2 years. The primary outcomes were clinical progression from MCI to all-cause dementia (regardless of suspected aetiology) or to AD dementia (AD as suspected aetiology). Prognostic performance was tested in a discovery cohort (n=331; mean age, 70.9 years; male, 58 percent, mean Mini-Mental State Examination score [MMSE] score, 27.1) and validated in a validation cohort (n=117).

In the discovery cohort, 110 patients with MCI progressed to dementia (71 to AD dementia). Notably, only tau PET showed better performance in predicting all-cause dementia (area under the receiver operating characteristic curve [AUC], 0.71; 95 percent confidence interval [CI], 0.65–0.77; p =0.02) vs base model of demographic characteristics, and this was replicated in the validation cohort. The models assessing Aß PET and MRI did not show improved prediction vs base model.

“To further maximize the potential clinical utility of our results, we will assess both dichotomized quantitative measures and visual reads, which are the most often implemented methods to score MRI and PET scans in the clinic,” added the researchers.

For prediction of AD dementia, only tau PET and tau PET visual read performed better than base model. Results showed an AUC of 0.84 (95 percent CI, 0.79–0.89; p<0.001) for tau PET and an AUC of 0.83 (95 percent CI, 0.78–0.88; p=0.001) for tau visual read, both of which could be validated. Although Aβ PET outperformed the base model (AUC, 0.83; 95 percent CI, 0.78–0.88; p=0.03) in the discovery cohort, the result could not be replicated in the validation cohort.

“Tau-PET showed the best performance as a standalone marker to predict progression to dementia in patients with MCI,” pointed out the researchers. “This suggests that tau PET scan may be the best currently available neuroimaging marker for prognostic purposes in MCI.”

Patients with MCI often experience considerable uncertainty and worry about future progression to dementia. In a recently published survey, “How quickly does my memory deteriorate?” was reported to be one of the most important questions for patients and caregivers. [Alzheimers Dement (N Y) 2021;7:e12189] “Our findings constitute a next step toward the ultimate goal of [obtaining] accurate and individualized prognoses, which may reduce uncertainty and lower disease burden for patients with MCI,” remarked the researchers.