Tau Positron Emission Tomography Breakthrough in Predicting Dementia in Mild Cognitive Impairment Patients: JAMA

The findings, published in JAMA Neurology, suggest that quantitative tau PET and tau PET visual reads are promising as stand-alone prognostic markers for clinical progression to dementia among individuals with mild cognitive impairment, outperforming Aβ PET and MRI.

In the cohort study, positivity on quantitative tau PET, but not Aβ PET or MRI better predicted the conversion from MCI to all-cause dementia when added to a base model including sex, age, education, and Mini-Mental State Examination score, while quantitative tau PET, as well as tau PET visual, reads improved prediction of Alzheimer's disease (AD) dementia. The optimal set of neuroimaging biomarkers to predict all-cause and AD dementia included tau PET and MRI measures.

An accurate prognosis is especially pertinent in mild cognitive impairment when individuals experience considerable uncertainty about future progression. Considering this, Colin Groot, Lund University, Lund, Sweden, and colleagues aimed to evaluate the tau PET's predictive value to predict clinical progression from MCI to dementia.

For this purpose, the researchers conducted a multicenter cohort study with external validation and a mean follow-up of 2.0 years. Data was collected from centers in Switzerland, the US, Sweden, and South Korea from 2014 to 2024. Participant data were retrospectively collected, and inclusion criteria were a baseline MCI diagnosis; longitudinal clinical follow-up; a Mini-Mental State Examination (MMSE) score greater than 22; and available tau PET, amyloid-β (Aβ) PET, and MRI scan less than one year from diagnosis.

The study included 448 eligible individuals with MCI (331 in the discovery cohort and 117 in the validation cohort). None of these participants were excluded from the study.

Positive results on Aβ PET (global; expressed in the standardized metric Centiloids), tau PET (temporal meta–region of interest), and MRI (Alzheimer's disease [AD] signature region) were assessed using quantitative thresholds and visual reads. The primary outcomes were clinical progression from MCI to all-cause dementia or AD dementia. The primary analyses were receiver operating characteristics.

The following were the key findings of the study:

• In the discovery cohort, the mean age was 70.9 years, 58% were male, the mean MMSE score was 1.9, and 110 individuals with MCI converted to dementia (71 to AD dementia).
• Only the model with tau PET predicted all-cause dementia (area under the receiver operating characteristic curve [AUC], 0.75) better than a base model including age, sex, education, and MMSE score (AUC, 0.71), while the models assessing the other neuroimaging markers did not improve prediction.
• In the validation cohort, tau PET was replicated in predicting all-cause dementia. Compared to the base model (AUC, 0.75), the prediction of AD dementia in the discovery cohort was significantly improved by including tau PET (AUC, 0.84), tau PET visual read (AUC, 0.83), and Aβ PET Centiloids (AUC, 0.83).
• In the validation cohort, only the tau PET and the tau PET visual reads replicated in predicting AD dementia.

"Tau-PET showed the best performance as a stand-alone marker to predict progression to dementia among individuals with MCI, suggesting that for prognostic purposes in MCI, a tau PET scan may be the best currently available neuroimaging marker," the researchers wrote.

Reference:

Groot C, Smith R, Collij LE, et al. Tau Positron Emission Tomography for Predicting Dementia in Individuals With Mild Cognitive Impairment. JAMA Neurol. Published online June 10, 2024. doi:10.1001/jamaneurol.2024.1612